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https://www.readbyqxmd.com/read/29132134/xia-yu-xue-decoction-inhibits-intestinal-epithelial-cell-apoptosis-in-ccl4-induced-liver-fibrosis
#1
Wenting Ma, Le Tao, Wei Zhang, Yinshen Zhu, Dongying Xue, Jie Zhang, Cheng Liu
BACKGROUND/AIMS: Intestine-derived endotoxin is thought to play a role in the development of liver fibrosis. However, the pathological change in the intestine during liver fibrosis is still poorly understood. Here, we investigated the effects of Xia-yu-xue decoction (XYXD) on intestinal inflammation, apoptosis, and tight junction integrity in the carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: Murine liver fibrosis was developed by CCI4 treatment three times per week over a 6-week period...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29127365/the-primary-cilium-is-necessary-for-the-differentiation-and-the-maintenance-of-human-adipose-progenitors-into-myofibroblasts
#2
N Arrighi, K Lypovetska, C Moratal, S Giorgetti-Peraldi, C A Dechesne, C Dani, P Peraldi
The primary cilium is an organelle, present at the cell surface, with various biological functions. We, and others, have shown that it plays a role in the differentiation of adipose progenitors (APs) into adipocytes. APs can also differentiate into myofibroblasts when treated with TGF-β1. Several components of the TGF-β1 pathway are located within the cilium suggesting a function for this organelle in AP myofibrogenesis. We studied differentiation of APs into myofibroblasts in two human models: APs of the adipose tissue (aAPs) and APs resident in the skeletal muscles (mAPs)...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121992/a-mouse-anti-myostatin-antibody-increases-muscle-mass-and-improves-muscle-strength-and-contractility-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-and-its-humanized-equivalent-domagrozumab-pf-06252616-increases-muscle-volume-in-cynomolgus-monkeys
#3
Michael St Andre, Mark Johnson, Prashant N Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M Burch, Peter Bialek, Carl Morris, Jane Owens
BACKGROUND: The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice...
November 9, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29100963/reversal-effects-of-low-dose-imatinib-compared-with-sunitinib-on-monocrotaline-induced-pulmonary-and-right-ventricular-remodeling-in-rats
#4
Zi Ping Leong, Ayumi Okida, Masahi Higuchi, Yoshiaki Yamano, Yoshiaki Hikasa
High-dose imatinib reverses cardiopulmonary remodeling but adverse effects limit its clinical use. Efficacy of the multi-kinase inhibitor sunitinib remains questionable. We compared anti-remodeling effects of imatinib with sunitinib on monocrotaline-induced right ventricular (RV) hypertrophy and pulmonary arterial remodeling in rats, focusing on a lower dose. Fourteen days after monocrotaline injection, oral gavage of imatinib (5, 15, or 50mg/kg), sunitinib (0.3, 1, 3, or 10mg/kg), or water for 14days was started...
October 31, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29093384/a-pilot-study-of-tranilast-for-cardiomyopathy-of-muscular-dystrophy
#5
Tsuyoshi Matsumura, Misa Matsui, Yuko Iwata, Masanori Asakura, Toshio Saito, Harutoshi Fujimura, Saburo Sakoda
Objective Heart failure is currently the most serious complication of muscular dystrophy. The transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a stretch-sensitive Ca channel. In damaged myocytes or cardiomyocytes, TRPV2 translocates to the cytoplasmic membrane and enhances Ca influx, triggering cell damage. Evidence suggests that the inhibition of TRPV2 may be a new therapeutic target in heart failure. We found that tranilast, which is widely used as an anti-allergic drug, inhibits TRPV2...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29078808/treatment-with-the-anti-il-6-receptor-antibody-attenuates-muscular-dystrophy-via-promoting-skeletal-muscle-regeneration-in-dystrophin-utrophin-deficient-mice
#6
Eiji Wada, Jun Tanihata, Akira Iwamura, Shin'ichi Takeda, Yukiko K Hayashi, Ryoichi Matsuda
BACKGROUND: Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles...
October 27, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29074396/translocation-and-dissemination-of-botulinum-neurotoxin-from-the-intestinal-tract
#7
Yukako Fujinaga, Michel R Popoff
Botulinum neurotoxins (BoNTs) are potent toxins which induce flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. They associate with non-toxic proteins (ANTPs or NAPs) to form complexes of various sizes which are resistant to acidic pH and protease degradation. BoNT trafficking from the digestive tract to the target neurons is still a matter of debate. BoNTs use different strategies to pass through the intestinal barrier including passage of BoNT complexes containing hemagglutinins (HAs) via M cells, HA-dependent perturbation of E-cadherin intercellular junctions between enterocytes and paracellular passage of BoNT complexes, and transcytosis of BoNT free of NAPs through certain intestinal epithelial cells...
October 23, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29065506/expression-profiling-of-differentiating-emerin-null-myogenic-progenitor-identifies-molecular-pathways-implicated-in-their-impaired-differentiation
#8
Ashvin Iyer, Adam J Koch, James M Holaska
Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD), a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells...
October 22, 2017: Cells
https://www.readbyqxmd.com/read/29057883/non-muscular-myosin-light-chain-kinase-triggers-intermittent-hypoxia-induced-interleukin-6-release-endothelial-dysfunction-and-permeability
#9
Sylvain Recoquillon, Manuel Gómez-Guzmán, Marion Rodier, Camille Koffi, Mathieu Nitiéma, Frédéric Gagnadoux, M Carmen Martínez, Ramaroson Andriantsitohaina
Obstructive sleep apnea is characterized by intermittent hypoxia (IH) which alters endothelial function, induces inflammation and accelerates atherosclerosis-induced cardiovascular diseases. The non-muscular myosin light chain kinase (nmMLCK) isoform contributes to endothelial cell-cell junction opening. Deletion of nmMLCK protects mice from death in septic shock models and prevents atherosclerosis in high-fat diet-fed mice. The aim of the study was to analyze the implication of nmMLCK in IH-induced vascular inflammation...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29057787/vitamin-d-in-pain-management
#10
REVIEW
Maria Helde-Frankling, Linda Björkhem-Bergman
Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain-but only in patients with insufficient levels of vitamin D when starting intervention...
October 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29045431/functional-improvement-of-dystrophic-muscle-by-repression-of-utrophin-let-7c-interaction
#11
Manoj K Mishra, Emanuele Loro, Kasturi Sengupta, Steve D Wilton, Tejvir S Khurana
Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal homolog of dystrophin and when overexpressed, can compensate for the absence of dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD. Utrophin is subject to miRNA mediated repression by several miRNAs including let-7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the repression' and increase utrophin expression...
2017: PloS One
https://www.readbyqxmd.com/read/29043208/phosphaturic-mesenchymal-tumor-pmt-exceptionally-rare-disease-yet-crucial-not-to-miss
#12
Amir Ghorbani-Aghbolaghi, Morgan Angus Darrow, Tao Wang
Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia...
July 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/29039450/insulin-restores-ucp3-activity-and-decreases-energy-surfeit-to-alleviate-lipotoxicity-in-skeletal-muscle
#13
Wenjuan Tang, Sunyinyan Tang, Hongdong Wang, Zhijuan Ge, Dalong Zhu, Yan Bi
An early insulin regimen ameliorates glucotoxicity but also lipotoxicity in type 2 diabetes; however, the underlying mechanism remains elusive. In the present study, we investigated the role of mitochondria in lipid regulation following early insulin administration in insulin-resistant skeletal muscle cells. Male C57BL/6 mice, fed a high-fat diet (HFD) for 8 weeks, were treated with insulin for 3 weeks, and L6 myotubes cultured with palmitate (PA) for 24 h were incubated with insulin for another 12 h. The results showed that insulin facilitated systemic glucose disposal and attenuated muscular triglyceride accumulation in vivo...
October 2, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29038293/loss-of-hepatic-amp-activated-protein-kinase-impedes-the-rate-of-glycogenolysis-but-not-gluconeogenic-fluxes-in-exercising-mice
#14
Curtis C Hughey, Freyja D James, Deanna P Bracy, E Patrick Donahue, Jamey D Young, Benoit Viollet, Marc Foretz, David H Wasserman
Pathologies including diabetes and conditions such as exercise place an unusual demand on liver energy metabolism, and this demand induces a state of energy discharge. Hepatic AMP-activated protein kinase (AMPK) has been proposed to inhibit anabolic processes such as gluconeogenesis in response to cellular energy stress. However, both AMPK activation and glucose release from the liver are increased during exercise. Here, we sought to test the role of hepatic AMPK in the regulation of in vivo glucose producing and citric acid cycle-related fluxes during an acute bout of muscular work...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28994701/study-of-statin-and-loratadine-induced-muscle-pain-mechanisms-using-human-skeletal-muscle-cells
#15
Yat Hei Leung, Jacques Turgeon, Veronique Michaud
Many drugs can cause unexpected muscle disorders, often necessitating the cessation of an effective medication. Inhibition of monocarboxylate transporters (MCTs) may potentially lead to perturbation of l-lactic acid homeostasis and muscular toxicity. Previous studies have shown that statins and loratadine have the potential to inhibit l-lactic acid efflux by MCTs (MCT1 and 4). The main objective of this study was to confirm the inhibitory potentials of atorvastatin, simvastatin (acid and lactone forms), rosuvastatin, and loratadine on l-lactic acid transport using primary human skeletal muscle cells (SkMC)...
October 10, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28994502/pro-protein-subtilisin-kexin-9-pcsk9-inhibition-in-practice-lipid-clinic-experience-in-2-contrasting-uk-centres
#16
Monika Kohli, Kinjal Patel, Zofia MacMahon, Radha Ramachandran, Martin A Crook, Timothy M Reynolds, Anthony S Wierzbicki
BACKGROUND: Prescribing criteria have been suggested for proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors but few studies exist of their real-world effectiveness. METHODS: This study audited PCSK-9 inhibitor therapy in 105 consecutive patients from two hospital centres-a university hospital (UH; n = 70) and a district general hospital (DGH; n = 35). Baseline characteristics including cardiovascular disease risk factors, NICE qualification criteria, efficacy and side effects were assessed...
October 10, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28978871/co-administration-of-myostatin-targeting-sirna-and-actriib-fc-fusion-protein-increases-masseter-muscle-mass-and-fiber-size
#17
Od Bayarsaikhan, Nobuhiko Kawai, Hiroyo Mori, Nao Kinouchi, Takeshi Nikawa, Eiji Tanaka
Myostatin, a member of the TGF-β superfamily, is a negative regulator of skeletal muscle cell growth and differentiation, and binds with high affinity to the activin type IIB receptor (ActRIIB). The soluble ligand-binding domain of ActRIIB fused to the Fc domain of IgG (ActRIIB-Fc) potently binds and inhibits TGF-β family members in muscle, leading to rapid and marked muscle growth. The present study was designed to assess the effectiveness of the co-delivery of myostatin-targeting siRNA (Mstn-siRNA) and ActRIIB-Fc into skeletal muscle as a potential treatment of atrophic myopathies...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/28978511/chronic-stress-inhibits-growth-and-induces-proteolytic-mechanisms-through-two-different-non-overlapping-pathways-in-the-skeletal-muscle-of-a-teleost-fish
#18
Cristián Andrés Valenzuela, Rodrigo Zuloaga, Luis Mercado, Ingibjörg Eir Einarsdottir, Bjorn Thrandur Bjornsson, Juan Antonio Valdes, Alfredo Molina
Chronic stress detrimentally affects animal health and homeostasis, with somatic growth, and thus skeletal muscle, being particularly affected. A detailed understanding of the underlying endocrine and molecular mechanisms of how chronic stress affects skeletal muscle growth remains lacking. To address this issue, the present study assessed primary (plasma cortisol), secondary (key components of the GH/IGF system, muscular proteolytic pathways and apoptosis), and tertiary (growth performance) stress responses in fine flounder (Paralichthys adspersus) exposed to crowding chronic stress...
October 4, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28977167/11%C3%AE-hydroxysteroid-dehydrogenase-type-ii-activity-is-affected-by-grapefruit-juice-and-intense-muscular-work
#19
Christopher Kargl, Mohammad Arshad, Fahad Salman, Regina C Schurman, Pedro Del Corral
OBJECTIVE: The enzymatic activity of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11β-HSD2 enzyme activity in vivo. SUBJECTS AND METHODS: Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order...
September 18, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28955765/identification-of-ligand-selective-peptidic-actriib-antagonists-using-phage-display-technology
#20
Kotaro Sakamoto, Yoko Kanematsu-Yamaki, Yusuke Kamada, Masahiro Oka, Toshiyuki Ohnishi, Masanori Miwa, Taiji Asami, Hiroshi Inooka
ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia...
September 2017: Biochemistry and Biophysics Reports
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