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https://www.readbyqxmd.com/read/28734203/exenatide-mitigated-diet-induced-vascular-aging-and-atherosclerotic-plaque-growth-in-apoe-deficient-mice-under-chronic-stress
#1
Guang Yang, Yanna Lei, Aiko Inoue, Limei Piao, Lina Hu, Haiying Jiang, Takeshi Sasaki, Hongxian Wu, Wenhu Xu, Chenglin Yu, Guangxian Zhao, Shinyu Ogasawara, Kenji Okumura, Masafumi Kuzuya, Xian-Wu Cheng
BACKGROUND AND AIMS: Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat (HF) diet. METHODS: ApoE(-/-) mice fed the HF diet were assigned to non-stressed and immobilized-stress groups for 12 weeks...
July 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28729415/an-essential-role-for-the-tumor-suppressor-merlin-in-regulating-fatty-acid-synthesis
#2
Dina S Stepanova, Galina Semenova, Yin-Ming Kuo, Andrew J Andrews, Sylwia Ammoun, C Oliver Hanemann, Jonathan Chernoff
Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system, most notably schwannomas and meningiomas. Mutational inactivation of the NF2 gene encoding the protein Merlin is found in most sporadic and inherited schwannomas, but the molecular mechanisms underlying neoplastic changes in schwannoma cells remain unclear. We report here that NF2-deficient cells display elevated expression levels of key enzymes involved in lipogenesis and that this upregulation is caused by increased activity of Torc1...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#3
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28729247/adaptive-regulation-of-pancreatic-acinar-mitochondrial-thiamin-pyrophosphate-uptake-process-possible-involvement-of-epigenetic-mechanism-s
#4
Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, Hamid M Said
The essentiality of thiamin stems from its roles as a co-factor (mainly in the form of thiamin pyrophosphate, TPP) in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive-regulation...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#5
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28728956/ataluren-in-patients-with-nonsense-mutation-duchenne-muscular-dystrophy-act-dmd-a-multicentre-randomised-double-blind-placebo-controlled-phase-3-trial
#6
Craig M McDonald, Craig Campbell, Ricardo Erazo Torricelli, Richard S Finkel, Kevin M Flanigan, Nathalie Goemans, Peter Heydemann, Anna Kaminska, Janbernd Kirschner, Francesco Muntoni, Andrés Nascimento Osorio, Ulrike Schara, Thomas Sejersen, Perry B Shieh, H Lee Sweeney, Haluk Topaloglu, Már Tulinius, Juan J Vilchez, Thomas Voit, Brenda Wong, Gary Elfring, Hans Kroger, Xiaohui Luo, Joseph McIntosh, Tuyen Ong, Peter Riebling, Marcio Souza, Robert J Spiegel, Stuart W Peltz, Eugenio Mercuri
BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. METHODS: We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America...
July 17, 2017: Lancet
https://www.readbyqxmd.com/read/28728277/-effects-of-pi3k%C3%AE-rhoa-pathway-on-phagocytosis-defect-of-alveolar-macrophages-in-a-mouse-model-of-chronic-obstructive-pulmonary-disease
#7
S T Hu, Q Xia, X L Zeng, H R Bao, X J Liu
Objective: To investigate effects of Phosphoinositide3-Kinases (PI3Kδ)-Ras homolog gene family member A(RhoA) pathway on phagocytosis deficiency of alveolar macrophages (AMs) in a mouse model of chronic obstructive pulmonary disease (COPD). Methods: Twenty mice were exposed to cigarette smoking to establish the COPD model, with 20 mice as the control group. AMs were isolated from lung tissue by discontinuous density gradient centrifugation and then divided into a healthy control group, a COPD group, a healthy IC87114 group and a COPD IC87114 group...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28727686/fbxw7-regulates-disc1-stability-via-the-ubiquitin-proteosome-system
#8
K Yalla, C Elliott, J P Day, J Findlay, S Barratt, Z A Hughes, L Wilson, E Whiteley, M Popiolek, Y Li, J Dunlop, R Killick, D R Adams, N J Brandon, M D Houslay, B Hao, G S Baillie
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28727085/impact-of-microbial-efficiency-to-predict-mp-supply-when-estimating-protein-requirements-of-growing-beef-cattle-from-performance
#9
A K Watson, T J Klopfenstein, G E Erickson, J C MacDonald, V A Wilkerson
Data from 16 trials were compiled to calculate microbial CP (MCP) production and MP requirements of growing cattle on high-forage diets. All cattle were individually fed diets with 28% to 72% corn cobs in addition to either alfalfa, corn silage, or sorghum silage at 18% to 60% of the diet (DM basis). The remainder of the diet consisted of protein supplement. Source of protein within the supplement varied and included urea, blood meal, corn gluten meal, dry distillers grains, feather meal, meat and bone meal, poultry by-product meal, soybean meal, and wet distillers grains...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726545/the-t-6-a-modification-acts-as-a-positive-determinant-for-the-anticodon-nuclease-prrc-and-is-distinctively-nonessential-in-streptococcus-mutans
#10
Jo Marie Bacusmo, Silvia S Orsini, Jennifer Hu, Michael DeMott, Patrick C Thiaville, Ameer Elfarash, Mellie June Paulines, Diego Rojas-Benítez, Birthe Meineke, Chris Deutsch, Dirk Iwata-Reuyl, Patrick A Limbach, Peter C Dedon, Kelly C Rice, Stewart Shuman, Valérie de Crécy-Lagard
Endoribonuclease toxins (ribotoxins) are produced by bacteria and fungi to respond to stress, eliminate non-self competitor species, or interdict virus infection. PrrC is a bacterial ribotoxin that targets and cleaves tRNA(Lys)UUU in the anticodon loop. In vitro studies suggested that the post-transcriptional modification threonylcarbamoyl adenosine (t(6)A) is required for PrrC activity but this prediction had never been validated in vivo. Here, by using t(6)A-deficient yeast derivatives, it is shown that t(6)A is a positive determinant for PrrC proteins from various bacterial species...
July 20, 2017: RNA Biology
https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#11
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
July 20, 2017: MAbs
https://www.readbyqxmd.com/read/28723560/crkl-mediates-p110%C3%AE-dependent-pi3k-signaling-in-pten-deficient-cancer-cells
#12
Jing Zhang, Xueliang Gao, Fabienne Schmit, Guillaume Adelmant, Michael J Eck, Jarrod A Marto, Jean J Zhao, Thomas M Roberts
The p110β isoform of PI3K is preferentially activated in many tumors deficient in the phosphatase and tensin homolog (PTEN). However, the mechanism(s) linking PTEN loss to p110β activation remain(s) mysterious. Here, we identify CRKL as a member of the class of PI3Kβ-interacting proteins. Silencing CRKL expression in PTEN-null human cancer cells leads to a decrease in p110β-dependent PI3K signaling and cell proliferation. In contrast, CRKL depletion does not impair p110α-mediated signaling. Further study showed that CRKL binds to tyrosine-phosphorylated p130Cas in PTEN-null cancer cells...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721806/l-tetrahydropalmatine-induces-apoptosis-in-eu-4-leukemia-cells-by-down-regulating-x-linked-inhibitor-of-apoptosis-protein-and-increases-the-sensitivity-towards-doxorubicin
#13
S Li, D Chen, Renzhi Pei, Y Lu, P Zhang, J Ma, X Liu, X Du, K Sha, L Chen, J Cao, X Zhuang, J Wu, L Li, Z Fan, P Ye, S Tang, B Zhang, X Shi, K Li
BACKGROUND: L-Tetrahydropalmatine (L-THP) is a tetra-hydro protoberberine isoquinoline alkaloid. The phyto-compounds bearing isoquinoline alkaloids have been reported to show a potential effect against a number of human cancers cell lines including leukemia. We hypothesized that L-THP, being an isoquinoline alkaloid, could be a potential molecule against acute lymphoblastic leukemia (ALL), in this study, we evaluate L-THP against p53 deficient leukemia EU-4 cell lines in vitro. METHODS: For the study, p53 null leukemia EU-4 cells were used and treated with L-THP...
July 18, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28721139/vitamin-d-deficiency-and-non-lipid-biomarkers-of-cardiovascular-risk
#14
Kamil F Faridi, Joshua R Lupton, Seth S Martin, Maciej Banach, Renato Quispe, Krishnaji Kulkarni, Steven R Jones, Erin D Michos
INTRODUCTION: Deficient 25-hydroxyvitamin D (25(OH)D) levels have been associated with dyslipidemia and cardiovascular diseases, though the underlying mechanism of these associations is uncertain. We analyzed associations between vitamin D and other non-lipid biomarkers of cardiovascular risk to better elucidate possible relationships between deficient 25(OH)D and cardiovascular disease. MATERIAL AND METHODS: We performed a cross-sectional analysis of 4,591 adults included in a clinical laboratory database from 2009 to 2011 with available measurements for 25(OH)D and the following biomarkers: homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), cystatin-C, creatinine, γ-glutamyltransferase (GGT), uric acid, and hemoglobin A1c (HbA1c)...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#15
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer generally associated with an aggressive clinical behavior. Here we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs) and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28717991/prolonged-bed-rest-impairs-rapid-cpi-17-phosphorylation-and-contraction-in-rat-mesenteric-resistance-arteries-to-cause-orthostatic-hypotension
#16
Toshio Kitazawa, Kazuyo Kitazawa
Prolonged bed rest (PBR) causes orthostatic hypotension (OH). Rapid constriction of splanchnic resistance arteries in response to a sudden increase in sympathetic tone contributes to the recovery of orthostatic arterial pressure upon standing. However, the molecular mechanism of PBR-induced dysfunction in arterial constriction is not fully understood. Previously, we showed that CPI-17, a regulatory protein for myosin phosphatase, mediates α1A-adrenergic receptor-induced rapid contraction of small mesenteric arteries...
July 17, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28716827/galectin-1-driven-tolerogenic-programs-aggravate-yersinia-enterocolitica-infection-by-repressing-antibacterial-immunity
#17
Roberto C Davicino, Santiago P Méndez-Huergo, Ricardo J Eliçabe, Juan C Stupirski, Ingo Autenrieth, María S Di Genaro, Gabriel A Rabinovich
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716731/arid1a-represses-hepatocellular-carcinoma-cell-proliferation-and-migration-through-lncrna-mvih
#18
Sheng Cheng, Lan Wang, Chuan-Huai Deng, Shi-Chun Du, Ze-Guang Han
ARID1A, encoding the BAF250a subunit of SWI/SNF complex, has a high mutation frequency in numerous types of cancer. LncRNAs, a type of non-coding RNAs longer than 200 nucleotides, have been reported to interplay with SWI/SNF complex during cancer progression. However, whether the interaction between ARID1A and lncRNA affects hepatocellular carcinoma (HCC) still needs to be investigated. Here, we reveal that ARID1A interacts with lncRNA MVIH through some region(s) or domain(s) including ARID domain and C-terminal ARID1A protein binding domain...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28716119/stat1-dependent-and-independent-pulmonary-allergic-and-fibrogenic-responses-in-mice-after-exposure-to-tangled-versus-rod-like-multi-walled-carbon-nanotubes
#19
Katherine S Duke, Alexia J Taylor-Just, Mark D Ihrie, Kelly A Shipkowski, Elizabeth A Thompson, Erinn C Dandley, Gregory N Parsons, James C Bonner
BACKGROUND: Pulmonary toxicity of multi-walled carbon nanotubes (MWCNTs) is influenced by physicochemical characteristics and genetic susceptibility. We hypothesized that contrasting rigidities of tangled (t) versus rod-like (r) MWCNTs would result in differing immunologic or fibrogenic responses in mice and that these responses would be exaggerated in transgenic mice lacking the signal transducer and activator of transcription-1 (STAT1), a susceptible mouse model of pulmonary fibrosis...
July 17, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28714586/activation-of-autophagy-is-involved-in-the-protective-effect-of-17%C3%AE-oestradiol-on-endotoxaemia-induced-multiple-organ-dysfunction-in-ovariectomized-rats
#20
Ming-Tzeung Chung, Yen-Mei Lee, Hsin-Hsueh Shen, Pao-Yun Cheng, Yu-Chen Huang, Yu-Ju Lin, Yu-Yang Huang, Kwok-Keung Lam
Oestrogens have been reported to attenuate acute inflammation in sepsis. In this study, the effects of long-term oestrogen replacement with 17β-oestradiol (E2 ) on endotoxaemia-induced circulatory dysfunction and multiple organ dysfunction syndrome were evaluated in ovariectomized (Ovx) rats. E2 (50 μg/kg, s.c., 3 times/week) was administered for 8 weeks, followed by the induction of endotoxaemia by intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg/4 hrs). Oestrogen deficiency induced by ovariectomy for 9 weeks augmented the LPS-induced damage, including endotoxic shock, myocardial contractile dysfunction, renal dysfunction and rhabdomyolysis...
July 17, 2017: Journal of Cellular and Molecular Medicine
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