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https://www.readbyqxmd.com/read/28343149/%C3%AE-adrenergic-stimulation-induces-histone-deacetylase-5-hdac5-nuclear-accumulation-in-cardiomyocytes-by-b55%C3%AE-pp2a-mediated-dephosphorylation
#1
Kate L Weeks, Antonella Ranieri, Agnieszka Karaś, Bianca C Bernardo, Alexandra S Ashcroft, Chris Molenaar, Julie R McMullen, Metin Avkiran
BACKGROUND: Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5...
March 25, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28342985/mast-cells-are-directly-activated-by-contact-with-cancer-cells-by-a-mechanism-involving-autocrine-formation-of-adenosine-and-autocrine-paracrine-signaling-of-the-adenosine-a3-receptor
#2
Yaara Gorzalczany, Eyal Akiva, Ofir Klein, Ofer Merimsky, Ronit Sagi-Eisenberg
Mast cells (MCs) constitute an important part of the tumor microenvironment (TME). However, their underlying mechanisms of activation within the TME remain poorly understood. Here we show that recapitulating cell-to-cell contact interactions by exposing MCs to membranes derived from a number of cancer cell types, results in MC activation, evident by the increased phosphorylation of the ERK1/2 MAP kinases and Akt, in a phosphatidylinositol 3-kinase dependent fashion. Activation is unidirectional since MC derived membranes do not activate cancer cells...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28340173/f-box-protein-fbx92-affects-leaf-size-in-arabidopsis-thaliana
#3
Joke Baute, Stefanie Polyn, Jolien De Block, Jonas Blomme, Mieke Van Lijsebettens, Dirk Inzé
F-box proteins are part of one of the largest families of regulatory proteins that play important roles in protein degradation. In plants, F-box proteins are functionally very diverse, and only a small subset has been characterized in detail. Here, we identified a novel F-box protein FBX92 as a repressor of leaf growth in Arabidopsis. Overexpression of AtFBX92 resulted in plants with smaller leaves than wild type, whereas plants with reduced levels of AtFBX92 showed in contrast increased leaf growth by stimulating cell proliferation...
March 14, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28339648/three-dimensional-testicular-organoid-a-novel-tool-for-the-study-of-human-spermatogenesis-and-gonadotoxicity-in-vitro%C3%A2
#4
Samuel S Pendergraft, Hooman Sadri-Ardekani, Anthony Atala, Colin E Bishop
Existing methods for evaluating the potential gonadotoxicity of environmental agents and pharmaceutical compounds rely heavily on animal studies. The current gold standard in vivo functional assays in animals are limited in their human predictive capacity. In addition, existing human two-dimensional in vitro models of testicular toxicity do not accurately reflect the in vivo situation. A more reliable testicular in vitro model system is needed to better assess the gonadotoxic potential of drugs prior to progression into clinical trials...
February 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339054/overexpression-of-tim-3-reduces-helicobacter-pylori-associated-inflammation-through-tlr4-nf%C3%AE%C2%BAb-signaling-in%C3%A2-vitro
#5
Fucai Wang, Zhirong Mao, Dongsheng Liu, Jing Yu, Youhua Wang, Wen Ye, Dongjia Lin, Nanjin Zhou, Yong Xie
The present study aimed to investigate the interaction between T-cell immunoglobulin and mucin-domain-containing molecule-3 (Tim-3) and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF‑κB) signaling in Helicobacter pylori-infected RAW264.7 macrophage cells. RAW264.7 cells were co‑cultured with H. pylori SS1 at different bacteria/cell ratios, and subsequently the mRNA expression of Tim‑3, TLR4, and myeloid differentiation factor 88 (MyD88) was measured by reverse transcription-quantitative polymerase chain reaction (RT‑qPCR)...
March 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339035/duration-of-simulated-microgravity-affects-the-differentiation-of-mesenchymal-stem-cells
#6
Li Xue, Yaohui Li, Jun Chen
Previous evidence has suggested that physical microenvironments and mechanical stresses, independent of soluble factors, influence mesenchymal stem cell (MSC) fate. In the present study, simulated microgravity (SMG) was demonstrated to regulate the differentiation of mesenchymal stem cells. This may be a novel strategy for tissue engineering and regenerative medicine. Rat MSCs were cultured for 72 h or 10 days in either normal gravity or a clinostat to model microgravity, followed with culture in diverse differential media...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339031/p53-inducible-long-non-coding-rna-picart1-mediates-cancer-cell-proliferation-and-migration
#7
Yu Cao, Minglin Lin, Yiwen Bu, Hongyan Ling, Yingchun He, Chenfei Huang, Yi Shen, Bob Song, Deliang Cao
Long non-coding RNAs (lncRNAs) function in the development and progression of cancer, but only a small portion of lncRNAs have been characterized to date. A novel lncRNA transcript, 2.53 kb in length, was identified by transcriptome sequencing analysis, and was named p53-inducible cancer-associated RNA transcript 1 (PICART1). PICART1 was found to be upregulated by p53 through a p53-binding site at -1808 to -1783 bp. In breast and colorectal cancer cells and tissues, PICART1 expression was found to be decreased...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28337129/novel-neuromodulation-techniques-to-assess-interhemispheric-communication-in-neural-injury-and-neurodegenerative-diseases
#8
REVIEW
Samuel S Shin, Galit Pelled
Interhemispheric interaction has a major role in various neurobehavioral functions. Its disruption is a major contributor to the pathological changes in the setting of brain injury such as traumatic brain injury, peripheral nerve injury, and stroke, as well as neurodegenerative diseases. Because interhemispheric interaction has a crucial role in functional consequence in these neuropathological states, a review of noninvasive and state-of-the-art molecular based neuromodulation methods that focus on or have the potential to elucidate interhemispheric interaction have been performed...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28337114/precondition-of-right-frontal-region-with-anodal-tdcs-can-restore-the-fear-memory-impairment-induced-by-acpa-in-male-mice
#9
Fariborz Manteghi, Mohammad Nasehi, Mohammad-Reza Zarrindast
Fear memory and learning cause behavioural patterns such as fight or flight responses, which increase survival probability, but unfit processing of fear memory and learning can lead to maladaptive behaviours and maladies such as phobias, Post-Traumatic Stress Disorder (PTSD) and anxiety disorders. The growing prevalence of these maladies shows the need to quest novel methods for their treatment. We used anodal transcranial direct current stimulation (tDCS) on the right frontal region as a precondition neuromodulator and arachidonylcyclopropylamide (ACPA), a selective CB1 cannabinoid receptor agonist, as a fear memory impairing agent to assess their effects on contextual and auditory fear conditioning (reliable model for fear studies)...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28336971/targeting-to-the-non-genomic-activity-of-retinoic-acid-receptor-gamma-by-acacetin-in-hepatocellular-carcinoma
#10
Wenjun Zeng, Chunyun Zhang, Hongwei Cheng, Yun-Long Wu, Jie Liu, Zekun Chen, Jian-Gang Huang, Russell Erick Ericksen, Liqun Chen, Haiping Zhang, Alice Sze Tsai Wong, Xiao-Kun Zhang, Weiping Han, Jin-Zhang Zeng
We recently demonstrated that retinoic acid receptor-γ (RARγ) is overexpressed and acts as a tumor promoter in hepatocellular carcinoma (HCC). The oncogenic activity of RARγ is mainly attributed to its physiological interaction with p85α regulatory subunit of PI3K leading to constitutive activation of AKT. Here we report RARγ as a negative regulator of p53 signaling and thus extend the oncogenic potential of RARγ to a new role in controlling the balance between AKT and p53. A natural flavonoid acacetin is then identified to be capable of modulating RARγ-dependent AKT-p53 network...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336813/the-innate-immune-response-in-fetal-lung-mesenchymal-cells-targets-vegfr2-expression-and-activity
#11
Rachel M Medal, Amanda M Im, Yasutoshi Yamamoto, Omar Lakhdari, Timothy S Blackwell, Hal M Hoffman, Debashis Sahoo, Lawrence S Prince
In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). Using Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336490/novel-therapeutic-interventions-for-pseudoachondroplasia
#12
Karen L Posey, Jacqueline T Hecht
Pseudoachondroplasia (PSACH), a severe short-limbed dwarfing condition, is associated with life-long joint pain and early onset osteoarthritis. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP), a pentameric matricellular protein expressed primarily in cartilage and other musculoskeletal tissues. Mutations in COMP diminish calcium binding and as a result perturb protein folding and export to the extracellular matrix. Mutant COMP is retained in the endoplasmic reticulum (ER) of growth plate chondrocytes resulting in massive intracellular COMP retention...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28336400/mechanistic-characterization-of-s-38093-a-novel-inverse-agonist-at-histamine-h3-receptors
#13
Aurore Sors, Fany Panayi, Lionel Bert, Dominique Favale, Olivier Nosjean, Valérie Audinot, Jean-Michel Arrang, Bruno Buisson, Esther Steidl, Jean-Marie Delbos, Tuulia Huhtala, Outi Kontkanen, Anne-Marie Chollet, Patrick Casara, Pierre Lestage
Histaminergic H3 inverse agonists, by stimulating central histamine release, represent attractive drug candidates to treat cognitive disorders. The present studies aimed to describe the mechanistic profile of S 38093 a novel H3 receptors inverse agonist. S 38093 displays a moderate affinity for rat, mouse and human H3 receptors (Ki = 8.8, 1.44 and 1.2µM, respectively) with no affinity for other histaminergic receptors. In cellular models, the compound was able to antagonize mice H3 receptors (KB = 0.65µM) and to suppress cAMP decrease induced by an H3 agonist via human H3 receptors (KB = 0...
March 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28336395/human-immune-compartment-comparisons-optimization-of-proliferative-assays-for-blood-and-gut-t-lymphocytes
#14
Jeffrey Dock, Lance Hultin, Patricia Hultin, Julie Elliot, Otto O Yang, Peter A Anton, Beth D Jamieson, Rita B Effros
The accumulation of peripheral blood late-differentiated memory CD8 T cells with features of replicative (cellular) senescence, including inability to proliferate in vitro, has been extensively studied. Importantly, the abundance of these cells is directly correlated with increased morbidity and mortality in older persons. Of note, peripheral blood contains only 2% of the total body lymphocyte population. By contrast, the gut-associated lymphoid tissue (GALT) is the most extensive lymphoid organ, housing up to 60% of total body lymphocytes, but has never been assessed with respect to senescence profiles...
March 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28336323/m1-muscarinic-activation-induces-long-lasting-increase-in-intrinsic-excitability-of-striatal-projection-neurons
#15
Xiaohui Lv, Jonathan W Dickerson, Jerri M Rook, Craig W Lindsley, P Jeffrey Conn, Zixiu Xiang
The dorsolateral striatum is critically involved in movement control and motor learning. Striatal function is regulated by a variety of neuromodulators including acetylcholine. Previous studies have shown that cholinergic activation excites striatal principal projection neurons, medium spiny neurons (MSNs), and this action is mediated by muscarinic acetylcholine subtype 1 receptors (M1) through modulating multiple potassium channels. In the present study, we used electrophysiology techniques in conjunction with optogenetic and pharmacological tools to determine the long-term effects of striatal cholinergic activation on MSN intrinsic excitability...
March 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28336292/structural-elucidation-and-physiologic-functions-of-specialized-pro-resolving-mediators-and-their-receptors
#16
REVIEW
Nan Chiang, Charles N Serhan
The acute inflammatory response is host protective to contain foreign invaders. Many of today's pharmacopeia that block pro-inflammatory chemical mediators can cause serious unwanted side effects such as immune suppression. Uncontrolled inflammation is now considered a pathophysiologic basis associated with, many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity and asthma, as well as the classic inflammatory diseases, e.g. arthritis, periodontal diseases...
March 20, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28336257/a-novel-pyrazole-containing-indolizine-derivative-suppresses-nf-%C3%AE%C2%BAb-activation-and-protects-against-tnbs-induced-colitis-via-a-ppar-%C3%AE-dependent-pathway
#17
Yong Fu, Junting Ma, Xiafei Shi, Xiang-Yun Song, Yaping Yang, Shuke Xiao, Jiahuang Li, Wei-Jin Gu, Zhen Huang, Junfeng Zhang, Jiangning Chen
The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD...
March 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28336086/incretin-hormones-regulate-microglia-oxidative-stress-survival-and-expression-of-trophic-factors
#18
Lindsay Joy Spielman, Deanna Lynn Gibson, Andis Klegeris
The incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are primarily known for their metabolic function in the periphery. GLP-1 and GIP are secreted by intestinal endocrine cells in response to ingested nutrients. Both GLP-1 and GIP stimulate the production and release of insulin from pancreatic β cells as well as exhibit several growth-regulating effects on peripheral tissues. GLP-1 and GIP are also present in the brain, where they provide modulatory and anti-apoptotic signals to neurons...
March 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#19
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28335658/dopamine-antagonists-for-treatment-resistance-in-autism-spectrum-disorders-review-and-focus-on-bdnf-stimulators-loxapine-and-amitriptyline
#20
Jessica A Hellings, L Eugene Arnold, Joan Han
Drug development is urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. At the same time, most psychiatric medications are drugs that have been repurposed following clinical observations of efficacy for a new treatment purpose. Areas Covered: This review aims to provide an overview of dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD, since they are a mainstay of treatment for such problems...
March 24, 2017: Expert Opinion on Pharmacotherapy
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