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https://www.readbyqxmd.com/read/27911337/effect-of-the-butyrate-prodrug-pivaloyloxymethyl-butyrate-an9-on-a-mouse-model-for-spinal-muscular-atrophy
#1
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/27911334/matrix-metalloproteinases-and-tissue-inhibitor-of-metalloproteinases-in%C3%A2-inflammation-and-fibrosis-of-skeletal-muscles
#2
Hala S Alameddine, Jennifer E Morgan
In skeletal muscles, levels and activity of Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs) have been involved in myoblast migration, fusion and various physiological and pathological remodeling situations including neuromuscular diseases. This has opened perspectives for the use of MMPs' overexpression to improve the efficiency of cell therapy in muscular dystrophies and resolve fibrosis. Alternatively, inhibition of individual MMPs in animal models of muscular dystrophies has provided evidence of beneficial, dual or adverse effects on muscle morphology or function...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27910868/relationship-between-nanotopographical-alignment-and-stem-cell-fate-with-live-imaging-and-shape-analysis
#3
Peter Newman, Jorge Luis Galenano-Niño, Pamela Graney, Joselito M Razal, Andrew I Minett, João Ribas, Raquel Ovalle-Robles, Maté Biro, Hala Zreiqat
The topography of a biomaterial regulates cellular interactions and determine stem cell fate. A complete understanding of how topographical properties affect cell behavior will allow the rational design of material surfaces that elicit specified biological functions once placed in the body. To this end, we fabricate substrates with aligned or randomly organized fibrous nanostructured topographies. Culturing adipose-derived stem cells (ASCs), we explore the dynamic relationship between the alignment of topography, cell shape and cell differentiation to osteogenic and myogenic lineages...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#4
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909292/crystal-structures-of-the-tric-trimeric-intracellular-cation-channel-orthologues
#5
Go Kasuya, Masahiro Hiraizumi, Andrés D Maturana, Kaoru Kumazaki, Yuichiro Fujiwara, Keihong Liu, Yoshiko Nakada-Nakura, So Iwata, Keisuke Tsukada, Tomotaka Komori, Sotaro Uemura, Yuhei Goto, Takanori Nakane, Mizuki Takemoto, Hideaki E Kato, Keitaro Yamashita, Miki Wada, Koichi Ito, Ryuichiro Ishitani, Motoyuki Hattori, Osamu Nureki
Ca(2+) release from the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER) is crucial for muscle contraction, cell growth, apoptosis, learning and memory. The trimeric intracellular cation (TRIC) channels were recently identified as cation channels balancing the SR and ER membrane potentials, and are implicated in Ca(2+) signaling and homeostasis. Here we present the crystal structures of prokaryotic TRIC channels in the closed state and structure-based functional analyses of prokaryotic and eukaryotic TRIC channels...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27908803/pericytes-integral-components-of-adult-hematopoietic-stem-cell-niches
#6
REVIEW
D Sá da Bandeira, J Casamitjana, M Crisan
The interest in perivascular cells as a niche for adult hematopoietic stem cells (HSCs) is significantly growing. In the adult bone marrow (BM), perivascular cells and HSCs cohabit. Among perivascular cells, pericytes are precursors of mesenchymal stem/stromal cells (MSCs) that are capable of differentiating into osteoblasts, adipocytes and chondrocytes. In situ, pericytes are recognised by their localisation to the abluminal side of the blood vessel wall, closely associated with endothelial cells in combination with the expression of markers such as CD146, neural glial 2 (NG2), platelet derived growth factor receptor β (PDGFRβ), α-smooth muscle actin (α-SMA), nestin (Nes) and/or leptin receptor (LepR)...
November 28, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27907103/tbx20-is-an-essential-regulator-of-embryonic-heart-growth-in-zebrafish
#7
Steffen Just, Linda Raphel, Ina M Berger, Anja Bühler, Mirjam Keßler, Wolfgang Rottbauer
The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein...
2016: PloS One
https://www.readbyqxmd.com/read/27906984/balance-and-muscle-strength-in-elderly-women-who-dance-samba
#8
Marcos Maurício Serra, Angelica Castilho Alonso, Mark Peterson, Luis Mochizuki, Júlia Maria D'Andréa Greve, Luiz Eugênio Garcez-Leme
Considering the growth of the aging population, and the increasing risk for falls and related morbidity, it is vital to seek efficient, comprehensive, and culturally relevant prevention programs for elderly people to reduce risks for falls. The aim of the present study was to evaluate the postural balance and muscle strength among women participating in the "Wing of Baianas" in the carnival parades. One hundred and ten women, with an average age of 67.4±5.9 years, were divided into two groups: Baianas group-elderly participants of the carnival parades in the "Wing of Baianas", and a Control group of women who do not dance samba...
2016: PloS One
https://www.readbyqxmd.com/read/27906635/a-specific-inhibitor-of-lactate-dehydrogenase-overcame-the-resistance-toward-gemcitabine-in-hypoxic-mesothelioma-cells-and-modulated-the-expression-of-the-human-equilibrative-transporter-1
#9
Elisa Giovannetti, Leticia G Leon, Valentina E Gómez, Paolo A Zucali, Filippo Minutolo, Godefridus J Peters
Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906092/alterations-to-mtorc1-signaling-in-the-skeletal-muscle-differentially-affect-whole-body-metabolism
#10
Maitea Guridi, Barbara Kupr, Klaas Romanino, Shuo Lin, Denis Falcetta, Lionel Tintignac, Markus A Rüegg
BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively...
March 21, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906069/the-beneficial-role-of-proteolysis-in-skeletal-muscle-growth-and-stress-adaptation
#11
REVIEW
Ryan A V Bell, Mohammad Al-Khalaf, Lynn A Megeney
Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery-the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage-and the critical role of these protein machines in establishing and preserving muscle health...
April 6, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906065/dystrophin-deficient-dogs-with-reduced-myostatin-have-unequal-muscle-growth-and-greater-joint-contractures
#12
Joe N Kornegay, Daniel J Bogan, Janet R Bogan, Jennifer L Dow, Jiahui Wang, Zheng Fan, Naili Liu, Leigh C Warsing, Robert W Grange, Mihye Ahn, Cynthia J Balog-Alvarez, Steven W Cotten, Monte S Willis, Candice Brinkmeyer-Langford, Hongtu Zhu, Joe Palandra, Carl A Morris, Martin A Styner, Kathryn R Wagner
BACKGROUND: Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition...
April 4, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906064/treatment-with-rgdf11-does-not-improve-the-dystrophic-muscle-pathology-of-mdx-mice
#13
Fabrizio Rinaldi, Yu Zhang, Ricardo Mondragon-Gonzalez, Jeffrey Harvey, Rita C R Perlingeiro
BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily and myostatin homologous, has been reported to have the capacity to reverse age-related skeletal muscle loss. These initial findings led us to investigate the ability of GDF11 to promote regeneration in the context of muscular dystrophy and determine whether it could be a candidate to slow down or reverse the disease progression in DMD...
June 14, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906050/the-sh3-and-cysteine-rich-domain-3-stac3-gene-is-important-to-growth-fiber-composition-and-calcium-release-from-the-sarcoplasmic-reticulum-in-postnatal-skeletal-muscle
#14
Xiaofei Cong, Jonathan Doering, Davi A G Mazala, Eva R Chin, Robert W Grange, Honglin Jiang
BACKGROUND: The SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac3 knockout mice. METHODS: We disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems. RESULTS: RT-qPCR and western blotting analyses of the limb muscles of target mice indicated that nearly all Stac3 mRNA and more than 70 % of STAC3 protein were deleted 4 weeks after tamoxifen injection...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905925/expression-of-insulin-receptor-ir-a-and-b-isoforms-igf-ir-and-ir-igf-ir-hybrid-receptors-in-vascular-smooth-muscle-cells-and-their-role-in-cell-migration-in-atherosclerosis
#15
N Beneit, C E Fernández-García, J L Martín-Ventura, L Perdomo, Ó Escribano, J B Michel, G García-Gómez, S Fernández, S Díaz-Castroverde, J Egido, A Gómez-Hernández, M Benito
BACKGROUND: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic process. In a previous work, we demonstrated that the insulin receptor isoform A (IRA) and its association with the insulin-like growth factor-I receptor (IGF-IR) confer a proliferative advantage to VSMCs. However, the role of IR and IGF-IR in VSMC migration remains poorly understood. METHODS: Wound healing assays were performed in VSMCs bearing IR (IRLoxP(+/+) VSMCs), or not (IR(-/-) VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs)...
December 1, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27905842/airway-smooth-muscle-cells-from-ovalbumin-sensitized-mice-show-increased-proliferative-response-to-tgf%C3%AE-1-due-to-up-regulation-of-smad3-and-tgf%C3%AE-rii
#16
Jianting Shi, Ming Chen, Lihua Ouyang, Linjie Huang, Xiaoling Lin, Wei Zhang, Ruiyun Liang, Zhiqiang Lv, Shanying Liu, Shanping Jiang
Transforming growth factor (TGF)-β1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFβ1 on proliferation of airway smooth muscle cells (ASMCs) are controversial. This study aimed to elucidate the role of TGFβ1 signaling in the proliferation of ASMCs by establishing an allergic model that mimics airway remodeling in chronic asthma and cell culture. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27905300/intravital-imaging-of-mouse-urothelium-reveals-activation-of-extracellular-signal-regulated-kinase-by-stretch-induced-intravesical-release-of-atp
#17
Takeshi Sano, Takashi Kobayashi, Hiromitsu Negoro, Atsushi Sengiku, Takuya Hiratsuka, Yuji Kamioka, Louis S Liou, Osamu Ogawa, Michiyuki Matsuda
To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#18
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27903395/-role-of-cytokine-matrix-metalloproteinase-axis-on-promoting-vascular-neointima-hyperplasia-in-mice
#19
Y Liu, W H Ning, X H Shen, D L Guo, L Guo
Objective: To observe the effects of tumor necrosis factor-α (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2(-/-)) mice and explore related mechanisms. Methods: Mice of control group, MMP9(-/-) group, MMP2(-/-) group and MMP9/2(-/-) group were studied. Femoral artery was injured by transluminal wire, the mRNA expression levels of TNF-α and PDGF on femoral artery were detected by RT-PCR; the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0, 1, 3, 7, 14 and 28 post injury...
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27902771/piceatannol-attenuates-renal-fibrosis-induced-by-unilateral-ureteral-obstruction-via-downregulation-of-histone-deacetylase-4-5-or-p38-mapk-signaling
#20
Sin Young Choi, Zhe Hao Piao, Li Jin, Jung Ha Kim, Gwi Ran Kim, Yuhee Ryu, Ming Quan Lin, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong
Piceatannol, a resveratrol metabolite, is a phenolic compound found in red wine and grapes. We investigated the effect of piceatannol on renal fibrosis and histone deacetylase (HDAC) expression in a mouse model of unilateral ureteral obstruction (UUO). Fibrosis was established by UUO and piceatannol was intraperitoneally injected for 2 weeks. Piceatannol suppressed extracellular matrix (ECM) protein deposition including collagen type I and fibronectin as well as connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in UUO kidneys...
2016: PloS One
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