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https://www.readbyqxmd.com/read/28214873/nel-like-molecule-1-nell1-is-regulated-by-bone-morphogenetic-protein-9-bmp9-and-potentiates-bmp9-induced-osteogenic-differentiation-at-the-expense-of-adipogenesis-in-mesenchymal-stem-cells
#1
Jing Wang, Junyi Liao, Fugui Zhang, Dongzhe Song, Minpeng Lu, Jianxiang Liu, Qiang Wei, Shengli Tang, Hao Liu, Jiaming Fan, Yulong Zou, Dan Guo, Jiayi Huang, Feng Liu, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Yaguang Weng, Michael J Lee, Tong-Chuan He, Russell R Reid, Jiye Zhang
BACKGROUND: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. METHODS: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis...
January 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214834/kidney-injury-molecule-1-is-elevated-in-nephropathy-and-mediates-macrophage-activation-via-the-mapk-signalling-pathway
#2
Lei Tian, Xinghua Shao, Yuanyuan Xie, Qin Wang, Xiajing Che, Minfang Zhang, Weijia Xu, Yao Xu, Shan Mou, Zhaohui Ni
BACKGROUND/AIMS: Kidney injury molecule-1 (KIM-1) is highly expressed in renal tubular cells after injury and is usually regarded as an early biomarker of acute kidney injury(AKI). The aim of this study was to determine the role of KIM-1 in the development of renal tubular injury Methods: Clinical samples, three different animal models and in vitro experiments were utilized to determine the possible mechanism underlying the involvement of KIM-1 in kidney injury. RESULTS: Both plasma and urinary KIM-1 expression levels were significantly higher in AKI and chronic kidney disease (CKD) patients than in healthy volunteers, and urinary KIM-1 expression was significantly higher in CKD patients than in AKI patients...
February 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214773/the-usefulness-of-bone-biomarkers-for-monitoring-treatment-disease-a-comparative-study-in-osteolytic-and-osteosclerotic-bone-metastasis-models
#3
Marta Martín-Fernández, Karmele Valencia, Carolina Zandueta, Cristina Ormazábal, Susana Martínez-Canarias, Fernando Lecanda, Concepción de la Piedra
BACKGROUND: The skeleton is the most common site of colonization by metastatic cancers. Zoledronic acid (ZA) has been shown to be effective for the treatment of bone metastases regardless of whether the bone lesions are osteolytic or osteoblastic. Biochemical markers of bone turnover may be useful tools to quantify the degree of bone remodeling in the presence of bone metastases. The aim of this work was to establish the correlation between tumor dispersion (bioluminescence) and biochemical markers of bone turnover in two osteolytic and osteoblastic metastasis models in mice...
February 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28214593/jak-stat-pathway-directed-therapy-of-t-cell-leukemia-lymphoma-inspired-by-functional-and-structural-genomics
#4
REVIEW
Thomas A Waldmann
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies. Activating mutations of STAT3/STAT5b and JAK1/3 were present in some but not in all cases with constitutive signaling pathway activation. Using shRNA analysis pSTAT malignant T-cell lines were addicted to JAKs/STATs whether they were mutated or not. Activating JAK/STAT mutations were not sufficient to support leukemic cell proliferation but only augmented upstream pathway signals...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28214591/hyperglycemia-is-associated-with-reduced-testicular-function-and-activin-dysregulation-in-the-ins2-akita-mouse-model-of-type-1-diabetes
#5
Constanze C Maresch, Dina C Stute, Helen Ludlow, Hans-Peter Hammes, David M de Kretser, Mark P Hedger, Thomas Linn
Type 1 diabetes (T1D) is associated with subfertility in men. We hypothesised that this results from inhibitory effects of chronic hyperglycemia on testicular function and used the Ins2(Akita ±) mouse model to investigate this. Diabetic mice exhibited progressive testicular dysfunction, with a 30% reduction in testis weight at 24 weeks of age. Diabetic mice showed significantly reduced seminiferous tubule diameters and increased spermatogenic disruption, although testes morphology appeared grossly normal. Unexpectedly, serum LH and intra-testicular testosterone were similar in all groups...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28214509/haplodeficiency-of-activin-receptor-like-kinase-4-alleviates-myocardial-infarction-induced-cardiac-fibrosis-and-preserves-cardiac-function
#6
Yi-He Chen, Qian Wang, Chang-Yi Li, Jian-Wen Hou, Xiao-Meng Chen, Qing Zhou, Jie Chen, Yue-Peng Wang, Yi-Gang Li
Cardiac fibrosis (CF), a repairing process following myocardial infarction (MI), is characterized by abnormal proliferation of cardiac fibroblasts and excessive deposition of extracellular matrix (ECM) resulting in inevitable resultant heart failure. TGF-β (transforming growth factor-β)/ALK5 (Activin receptor-like kinase 5)/Smad2/3/4 pathways have been reported to be involved in the process. Recent studies have implicated both activin and its specific downstream component ALK4 in stimulating fibrosis in non-cardiac organs...
February 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28214380/application-of-the-mechpeff-model-to-predict-passive-effective-intestinal-permeability-in-the-different-regions-of-the-rodent-small-intestine-and-colon
#7
D Pade, M Jamei, A Rostami-Hodjegan, D B Turner
A major component of Physiologically-Based Pharmacokinetic (PBPK) models is prediction of the rate and extent of absorption of orally dosed drugs for which knowledge of effective passive intestinal permeability (Peff ) is essential. Single pass intestinal perfusion (SPIP) studies are used to establish effective permeability in vivo but are difficult to perform in rodents while mechanistic models to predict drug Peff in rat and mouse have not been published. This work evaluates the predictive performance of the 'MechPeff' model to predict Peff in the rodent intestine based upon knowledge of regional gut physiology and drug-specific physicochemical parameters...
February 18, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28214283/prognostic-role-of-n-cadherin-expression-in-patients-with-non-muscle-invasive-bladder-cancer
#8
Mohammad Abufaraj, Shahrokh F Shariat, Andrea Haitel, Marco Moschini, Beat Foerster, Piotr Chłosta, Kilian Gust, Marek Babjuk, Alberto Briganti, Pierre I Karakiewicz, Walter Albrecht
PURPOSE: To assess the role of N-cadherin as a prognostic biomarker in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection with or without adjuvant intravesical therapy. PATIENTS AND METHODS: Immunohistochemistry using monoclonal mouse antibody was used to evaluate the expression status of N-cadherin in 827 patients with NMIBC. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected...
February 14, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28214198/tumor-derived-cd4-cd25-regulatory-t-cells-inhibit-dendritic-cells-function-by-ctla-4
#9
Xin Chen, Yong Du, Qingqing Hu, ZhiMing Huang
PURPOSE: CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way...
December 21, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213942/pge2-ep4-attenuated-mucosal-injury-via-%C3%AE-arr1-src-egfr-mediated-proliferation-in-portal-hypertensive-gastropathy
#10
Siwei Tan, Xiaoliang Chen, Minyi Xu, Xiaoli Huang, Huiling Liu, Jie Jiang, Yu Lu, Xiaojie Peng, Bin Wu
BACKGROUND AND PURPOSE: Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients associated with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role of prostaglandin E2 (PGE2 ) and its E-type prostanoid 4 (EP4 ) receptor in the promotion of mucosal proliferation. However, whether β-arrestin1 (β-arr1), a well-established mediator of G-protein-coupled receptors (GPCRs), is involved in the PGE2 /EP4 -mediated mucosal proliferation complex in PHG remains unclear...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#11
Kevin D Quinn, Michaela Schedel, Yasmeen Nkrumah-Elie, Anthony Joetham, Michael Armstrong, Charmion Cruickshank-Quinn, Richard Reisdorph, Erwin W Gelfand, Nichole Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213749/effect-of-continuous-sub-culturing-on-infectivity-of-clostridium-perfringens-atcc13124-in-mouse-gas-gangrene-model
#12
Ravi Bhushan Kumar, Syed Imteyaz Alam
Clostridium perfringens is a Validated Biological Agent and a pathogen of medical, veterinary, and military significance. Gas gangrene is the most destructive of all the clostridial diseases and is caused by C. perfringens type A strains wherein the infection spreads quickly (several inches per hour) with production of gas. Influence of repeated in vitro cultivation on the infectivity of C. perfringens was investigated by comparing the surface proteins of laboratory strain and repository strains of the bacterium using 2DE-MS approach...
February 17, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#13
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#14
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#15
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213494/plc%C3%AE%C2%B51-regulates-sdf-1%C3%AE-induced-lymphocyte-adhesion-and-migration-to-sites-of-inflammation
#16
Marianne Strazza, Inbar Azoulay-Alfaguter, Michael Peled, Alan V Smrcka, Edward Y Skolnik, Shekhar Srivastava, Adam Mor
Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Cε 1 (PLCε1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213444/the-dendrites-of-ca2-and-ca1-pyramidal-neurons-differentially-regulate-information-flow-in-the-cortico-hippocampal-circuit
#17
Kalyan V Srinivas, Eric W Buss, Qian Sun, Bina Santoro, Hiroto Takahashi, Daniel A Nicholson, Steven A Siegelbaum
The impact of a given neuronal pathway depends on the number of synapses it makes with its postsynaptic target, the strength of each individual synapse and the integrative properties of the postsynaptic dendrites. Here we explore the cellular and synaptic mechanisms responsible for the differential excitatory drive from the entorhinal cortical pathway onto mouse CA2 compared to CA1 pyramidal neurons (PNs). Although both types of neurons receive direct input from entorhinal cortex onto their distal dendrites, these inputs produce a 5-6 fold larger excitatory postsynaptic potential (EPSP) at the soma of CA2 compared to CA1 PNs, which is sufficient to drive action potential output from CA2 but not CA1...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213294/a-low-cost-simplified-and-scaleable-pneumotachograph-and-face-mask-for-neonatal-mouse-respiratory-measurements
#18
Jenny J Sun, Roshan Nanu, Russell S Ray
INTRODUCTION: Neonatal respiratory disorders are a leading cause of perinatal mortality due to complications resulting from premature births and prenatal exposure to drugs of abuse, but optimal treatments for these symptoms are still unclear due to a variety of confounds and risk factors. Mouse models present an opportunity to study the underlying mechanisms and efficacy of potential treatments of these conditions with controlled variables. However, measuring respiration in newborn mice is difficult and commercial components are expensive and often require modification, creating a barrier and limiting our understanding of the short and long-term effects of birth complications on respiratory function...
February 14, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#19
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28213125/reduced-bioavailable-manganese-causes-striatal-urea-cycle-pathology-in-huntington-s-disease-mouse-model
#20
Terry Jo V Bichell, Michal Wegrzynowicz, K Grace Tipps, Emma M Bradley, Michael A Uhouse, Miles Bryan, Kyle Horning, Nicole Fisher, Karrie Dudek, Timothy Halbesma, Preethi Umashanker, Andrew D Stubbs, Hunter K Holt, Gunnar F Kwakye, Andrew M Tidball, Roger J Colbran, Michael Aschner, M Diana Neely, Alba Di Pardo, Vittorio Maglione, Alexander Osmand, Aaron B Bowman
Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model...
February 14, 2017: Biochimica et Biophysica Acta
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