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https://www.readbyqxmd.com/read/27913661/effects-of-exendin-4-on-the-intrarenal-renin-angiotensin-system-and-interstitial-fibrosis-in-unilateral-ureteral-obstruction-mice-exendin-4-and-unilateral-ureteral-obstruction
#1
Ying Le, Zongji Zheng, Junyu Xue, Mengling Cheng, Meiping Guan, Yaoming Xue
OBJECTIVE: The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms. METHODS: Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27911337/effect-of-the-butyrate-prodrug-pivaloyloxymethyl-butyrate-an9-on-a-mouse-model-for-spinal-muscular-atrophy
#2
Jonathan D Edwards, Matthew E R Butchbach
Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27907033/normalization-of-patient-identified-plasma-biomarkers-in-smn%C3%AE-7-mice-following-postnatal-smn-restoration
#3
W David Arnold, Sandra Duque, Chitra C Iyer, Phillip Zaworski, Vicki L McGovern, Shannon J Taylor, Katharine M von Herrmann, Dione T Kobayashi, Karen S Chen, Stephen J Kolb, Sergey V Paushkin, Arthur H M Burghes
INTRODUCTION AND OBJECTIVE: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function...
2016: PloS One
https://www.readbyqxmd.com/read/27906172/inflammatory-macrophages-can-transdifferentiate-into-myofibroblasts-during-renal-fibrosis
#4
Xiao-Ming Meng, Shuang Wang, Xiao-Ru Huang, Chen Yang, Jun Xiao, Yang Zhang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan
Myofibroblasts play a central role in renal fibrosis although the origin of these cells remains controversial. We recently reported that bone marrow-derived macrophages can give rise to myofibroblasts through macrophage to myofibroblast transition (MMT). However, several important issues remain to be addressed, including whether MMT occurs in human kidney disease and verification of the MMT process through lineage tracing. Biopsies from a cohort of 58 patients with various forms of kidney disease were examined for MMT cells that co-express macrophage (CD68) and myofibroblast (α-smooth muscle actin, α-SMA) markers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27894619/expression-of-pro-fibrotic-and-anti-fibrotic-molecules-in-dimethylnitrosamine-induced-hepatic-fibrosis
#5
Roberta Sferra, Antonella Vetuschi, Simona Pompili, Eugenio Gaudio, Silvia Speca, Giovanni Latella
BACKGROUND: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors. OBJECTIVE: To evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice...
November 11, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27882347/ml372-blocks-smn-ubiquitination-and-improves-spinal-muscular-atrophy-pathology-in-mice
#6
Mahlet B Abera, Jingbo Xiao, Jonathan Nofziger, Steve Titus, Noel Southall, Wei Zheng, Kasey E Moritz, Marc Ferrer, Jonathan J Cherry, Elliot J Androphy, Amy Wang, Xin Xu, Christopher Austin, Kenneth H Fischbeck, Juan J Marugan, Barrington G Burnett
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease and one of the leading inherited causes of infant mortality. SMA results from insufficient levels of the survival motor neuron (SMN) protein, and studies in animal models of the disease have shown that increasing SMN protein levels ameliorates the disease phenotype. Our group previously identified and optimized a new series of small molecules, with good potency and toxicity profiles and reasonable pharmacokinetics, that were able to increase SMN protein levels in SMA patient-derived cells...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27877076/cardiomyogenic-differentiation-of-human-dental-follicle-derived-stem-cells-by-suberoylanilide-hydroxamic-acid-and-their-in-vivo-homing-property
#7
Iel-Yong Sung, Han-Na Son, Imran Ullah, Dinesh Bharti, Ju-Mi Park, Yeong-Cheol Cho, June-Ho Byun, Young-Hoon Kang, Su-Jin Sung, Jong-Woo Kim, Gyu-Jin Rho, Bong-Wook Park
The purpose of the present study was to investigate the in vitro cardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze the in vivo homing capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27876854/mir-706-inhibits-the-oxidative-stress-induced-activation-of-pkc%C3%AE-taok1-in-liver-fibrogenesis
#8
Ruili Yin, Duo Guo, Shuxian Zhang, Xiuying Zhang
Oxidative stress induces the activation of liver fibrogenic cells (myofibroblasts), thus promoting the expression of fibrosis-related genes, leading to hepatic fibrogenesis. MicroRNAs (miRNAs) are a new class of small RNAs ~18-25 nucleotides in length involved in post-transcriptional regulation of gene expression. Wound-healing and remodeling processes in liver fibrosis have been associated with changes in hepatic miRNA expression. However, the role of miR-706 in liver fibrogenesis is currently unknown. In the present study, we show that miR-706 is abundantly expressed in hepatocytes...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27875740/conditional-knockout-of-tfpi-1-in-vsmcs-of-mice-accelerates-atherosclerosis-by-enhancing-amot-yap-pathway
#9
Jiajun Xiao, Kaiyue Jin, Jiping Wang, Jing Ma, Jin Zhang, Nan Jiang, Huijun Wang, Xinping Luo, Jian Fei, Zhugang Wang, Xiao Yang, Duan Ma
BACKGROUND: Tissue factor pathway inhibitor-1 (TFPI-1) has multiple functions and its precise role and molecular mechanism during the development of atherosclerosis are not clear. OBJECTIVES: To determine the effect and molecular mechanism of TFPI-1 deficiency in vascular smooth muscle cells (VSMCs) in atherosclerosis in the apolipoprotein E knockout (ApoE(-/-)) mouse. METHODS AND RESULTS: A mouse model with a conditional knockout of TFPI-1 in VSMCs in an atherosclerosis-prone background (ApoE(-/-)) was generated...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27872076/anti-schistosomiasis-liver-fibrosis-effects-of-chlorogenic-acid-through-il-13-mir-21-smad7-signaling-interactions-in-vivo-and-in-vitro
#10
Yao Wang, Fan Yang, Jun Xue, Xuan Zhou, Lei Luo, Qian Ma, Yun-Fei Chen, Juan Zhang, Shu-Ling Zhang, Lei Zhao
This study is to investigate the anti-Schistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on IL-13/miR-21/Smad7 signaling interactions in hepatic stellate LX2 cell line and Schistosome-infected mice. The transfection was based on the GV273-miR-21-EGFP and GV369-miR-21-EGFP lentiviral system to up- or down-regulate miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7 and connective tissue growth factor (CTGF) and protein expression of Smad7, CTGF, Smad1, p-Smad1, Smad2, p-Smad2, Smad2/3, p-Smad2/3, TGF-β receptor I and α-SMA were assayed...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27870967/osthole-inhibits-the-expressions-of-collagen-i-and-iii-through-smad-signaling-pathway-after-treatment-with-tgf-%C3%AE-1-in-mouse-cardiac-fibroblasts
#11
Jin-Cheng Liu, Feng Wang, Mei-Lin Xie, Zong-Qi Cheng, Qiong Qin, Lin Chen, Rong Chen
BACKGROUND: Osthole, a natural coumarin and bioactive compound isolated from the fruit of Cnidium monnieri (L.) Cusson, was reported to prevent isoprenaline-induced myocardial fibrosis in mice by inhibiting the transforming growth factor-β1 (TGF-β1) expression, but the underlying mechanism is still unclear. The aim of this study is to illuminate whether the mechanism of osthole inhibiting collagen I and III expressions is associated with Smad signaling pathway in mouse cardiac fibroblasts (CFs) treated with TGF-β1...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27870893/activin-receptor-type-iib-inhibition-improves-muscle-phenotype-and-function-in-a-mouse-model-of-spinal-muscular-atrophy
#12
Min Liu, David W Hammers, Elisabeth R Barton, H Lee Sweeney
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disorder that causes progressive muscle atrophy and weakness. Using adeno-associated virus-mediated gene transfer, we evaluated the potential to improve skeletal muscle weakness via systemic, postnatal inhibition of either myostatin or all signaling via the activin receptor type IIB (ActRIIB). After demonstrating elevated p-SMAD3 content and differential content of ActRIIB ligands, 4-week-old male C/C SMA model mice were treated intraperitoneally with 1x1012 genome copies of pseudotype 2/8 virus encoding a soluble form of the ActRIIB extracellular domain (sActRIIB) or protease-resistant myostatin propeptide (dnMstn) driven by a liver specific promoter...
2016: PloS One
https://www.readbyqxmd.com/read/27866296/intranasal-curcumin-inhibits-pulmonary-fibrosis-by-modulating-matrix-metalloproteinase-9-mmp-9-in-ovalbumin-induced-chronic-asthma
#13
Preeti S Chauhan, D Dash, Rashmi Singh
Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week)...
November 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27864286/transforming-growth-factor-%C3%AE-plays-divergent-roles-in-modulating-vascular-remodeling-inflammation-and-pulmonary-fibrosis-in-a-murine-model-of-scleroderma
#14
Kazuyuki Tsujino, Nilgun Isik Reed, Amha Atakilit, Xin Ren, Dean Sheppard
The efficacy and feasibility of targeting TGF-β in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study, we analyzed how blocking TGF-β signaling affects pulmonary abnormalities in fos-related antigen 2 (Fra-2) transgenic mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGF-β signaling in the Fra-2 transgenic mice, we used a pan-TGF-β blocking antibody, 1D11, and transgenic mice in which TGF-β receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER; Tgfbr2flox/flox)...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27860388/enhanced-tissue-remodeling-efficacy-of-adipose-derived-mesenchymal-stem-cells-using-injectable-matrices-in-radiation-damaged-salivary-gland-model
#15
Jeong-Seok Choi, Hye-Young An, Hyun-Soo Shin, Young-Mo Kim, Jae-Yol Lim
The present study was conducted to introduce the use of a delivery carrier for local transplantation of human adipose tissue-derived mesenchymal stem cells (AdMSCs) into the salivary gland (SG) and analyze its ability to enhance radioprotection of AdMSCs against irradiation (IR)-induced damage. An injectable porcine small intestinal submucosa (SIS) matrix was used as a cell delivery carrier and human AdMSCs were contained within SIS hydrogel (AdMSC/SIS). After local injection into SGs of mice following local IR, morphological and functional changes were evaluated in the sham, vehicle (PBS), SIS, AdMSC, and AdMSC/SIS groups...
November 12, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27856416/regulation-and-function-of-bone-morphogenetic-protein-signaling-in-colonic-injury-and-inflammation
#16
Tuo Ji, Hidehiko Takabayashi, Maria Mao, Xu Han, Xiang Xue, Jennifer C Brazil, Kathryn A Eaton, Yatrik M Shah, Andrea Todisco
The bone morphogenetic proteins (BMPs) regulate gastrointestinal homeostasis. We investigated the expression of BMP-4 and the localization and function of BMP signaling during colonic injury and inflammation. Wild type mice and mice expressing the β-galactosidase (β-gal) gene under the control of a BMP responsive element (BRE), BMP-4-β-gal/+ mice, and animals generated by crossing villin-Cre mice to mice with floxed alleles of BMP receptor 1A (villin-Cre;Bmpr1a(flox/flox)), were treated with DSS to induce colonic injury and inflammation...
November 17, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27853171/de-ubiquitinating-enzyme-usp11-promotes-transforming-growth-factor-%C3%AE-1-signaling-through-stabilization-of-transforming-growth-factor-%C3%AE-receptor-ii
#17
A M Jacko, L Nan, S Li, J Tan, J Zhao, D J Kass, Y Zhao
The transforming growth factor β-1 (TGFβ-1) signaling pathway plays a central role in the pathogenesis of pulmonary fibrosis. Two TGFβ-1 receptors, TβRI and TβRII, mediate this pathway. TβRI protein stability, as mediated by the ubiquitin/de-ubiquitination system, has been well studied; however, the molecular regulation of TβRII still remains unclear. Here we reveal that a de-ubiquitinating enzyme, USP11, promotes TGFβ-1 signaling through de-ubiquitination and stabilization of TβRII. We elucidate the role that mitoxantrone (MTX), an USP11 inhibitor, has in the attenuation of TGFβ-1 signaling...
November 17, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27853137/cug-binding-protein-1-regulates-hsc-activation-and-liver-fibrogenesis
#18
Xingxin Wu, Xudong Wu, Yuxiang Ma, Fenli Shao, Yang Tan, Tao Tan, Liyun Gu, Yang Zhou, Beicheng Sun, Yang Sun, Xuefeng Wu, Qiang Xu
Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. Here we report that CUG-binding protein 1 (CUGBP1) expression is elevated in HSCs and positively correlates with liver fibrosis severity in human liver biopsies. Transforming growth factor-beta (TGF-β) selectively increases CUGBP1 expression in cultured HSCs in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Knockdown of CUGBP1 inhibits alpha smooth muscle actin (α-SMA) expression and promotes interferon gamma (IFN-γ) production in HSCs in vitro...
November 17, 2016: Nature Communications
https://www.readbyqxmd.com/read/27851781/characterization-of-a-novel-dermal-fibrosis-model-induced-by-areca-nut-extract-that-mimics-oral-submucous-fibrosis
#19
Min-Hsuan Chiang, Ping-Ho Chen, Yuk-Kwan Chen, Chia-Hsin Chen, Mei-Ling Ho, Yan-Hsiung Wang
Oral submucous fibrosis (OSF) is an oral potentially malignant disorder and areca quid chewing is the main etiological factor. However, the molecular mechanism underlying OSF remains unclear, partly due to the lack of an appropriate animal model. The present study aimed to establish and characterize an animal model of areca nut extract (ANE)-induced skin fibrosis that mimics OSF. Mice were divided into 4 groups: the control group; the bleomycin group; and the ANE10 and ANE20 groups, which received 10mg/ml and 20mg/ml subcutaneous (SC) injection of ANE, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27848249/cystathionine-%C3%AE-lyase-deficiency-exacerbates-ccl4-induced-acute-hepatitis-and-fibrosis-in-the-mouse-liver
#20
Lei Ci, Xing Yu Yang, Xiao Wen Gu, Qing Li, Yang Guo, Zi Ping Zhou, Meng Jie Zhang, Jia Hao Shi, Hua Yang, Zhu Gang Wang, Jian Fei
AIMS: The present study examined the role of cystathionine γ-lyase (CSE) in CCl4- induced liver damage. RESULTS: A CSE gene knock-out and luciferase gene knock-in mouse model was constructed to study the function of CSE and trace its expression in living status. CCl4 or LPS markedly downregulated CSE expression in the liver of mice. CSE-deficient mice showed increased serum alanine aminotransferase and aspartate aminotransferase levels, and liver damage after CCl4 challenge, whereas albumin and endogenous H2S levels decreased significantly...
November 16, 2016: Antioxidants & Redox Signaling
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