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https://www.readbyqxmd.com/read/29156756/mir-221-regulated-kit-level-by-wild-type-or-leukemia-mutant-runx1-a-determinant-of-single-myeloblast-fate-decisions-that-collectively-drives-or-hinders-granulopoiesis
#1
Stefano Rossetti, Michael J Anauo, Nicoletta Sacchi
RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32D(miR-ON-221) myeloblasts expressing wild type RUNX1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156748/association-of-melatonin-membrane-receptor-1a-1b-gene-polymorphisms-with-the-occurrence-and-metastasis-of-hepatocellular-carcinoma
#2
Shih-Chi Su, Yung-Chuan Ho, Yu-Fan Liu, Russel J Reiter, Chia-Hsuan Chou, Chia-Ming Yeh, Hsiang-Lin Lee, Wen-Hung Chung, Ming-Ju Hsieh, Shun-Fa Yang
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#3
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156655/the-role-of-glyoxalase-i-glo-i-advanced-glycation-endproducts-ages-and-their-receptor-rage-in-chronic-liver-disease-and-hepatocellular-carcinoma-hcc
#4
REVIEW
Marcus Hollenbach
Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC)...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156528/actein-ameliorates-hepatic-steatosis-and-fibrosis-in-high-fat-diet-induced-nafld-by-regulation-of-insulin-and-leptin-resistant
#5
Hong-Jun Chen, Jin Liu
Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#6
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155882/pharmacological-inhibition-of-ror%C3%AE-t-suppresses-the-th17-pathway-and-alleviates-arthritis-in-vivo
#7
Ulf Guendisch, Jessica Weiss, Florence Ecoeur, Julia Christina Riker, Klemens Kaupmann, Joerg Kallen, Samuel Hintermann, David Orain, Janet Dawson, Andreas Billich, Christine Guntermann
Retinoic acid receptor-related-orphan-receptor-C (RORγt) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORγt in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim of inhibiting the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in vitro and in vivo pharmacology of a potent and selective small-molecular-weight RORγt inverse agonist...
2017: PloS One
https://www.readbyqxmd.com/read/29155585/allosteric-inhibitors-of-shp2-with-therapeutic-potential-for-cancer-treatment
#8
Jingjing Xie, Xiaojia Si, Shoulai Gu, Mingliang Wang, Jian Shen, Haoyan Li, Jian Shen, Dan Li, Yanjia Fang, Cong Liu, Jidong Zhu
SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, is involved in multiple cell signaling processes including Ras/MAPK and Hippo/YAP pathways. SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric and breast cancer. It also regulates T-cell activation by interacting with inhibitory immune checkpoint receptors such as the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). Thus, SHP2 inhibitors have drawn great attention by both inhibiting tumor cell proliferation and activating T cell immune responses toward cancer cells...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#9
Sandra Aurora Niño, Guadalupe Martel-Gallegos, Adriana Castro-Zavala, Benita Ortega-Berlanga, Juan Manuel Delgado, Hector Hernandez-Mendoza, E Romero-Guzman, Judith Rios-Lugo, Sergio Rosales-Mendoza, María Esther Jiménez-Capdeville, Sergio Zarazua
Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life.1,2 In this study, the effects of chronic exposure to inorganic arsenic (3 ppm by drinking water) in Wistar rats on the production and elimination of Amyloid-β (Aβ) were evaluated...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29155331/evolution-of-vomeronasal-receptor-1-v1r-genes-in-the-common-marmoset-callithrix-jacchus
#10
Keiko Moriya-Ito, Takashi Hayakawa, Hikoyu Suzuki, Kimiko Hagino-Yamagishi, Masato Nikaido
Pheromones are crucial for eliciting innate responses and inducing social and sexual behaviors in mammals. The vomeronasal receptor 1 genes, V1Rs, encode members of a pheromone receptor family that are mainly expressed in the vomeronasal organ (VNO). The V1R family shows extraordinary variety in gene number among vertebrates owing to successive gene gains and losses during evolution. Such diversity is believed to reflect a degree of dependence on the VNO. We investigated V1R evolution in primate lineages closely related to humans because these VNOs show a trend toward degeneration...
November 16, 2017: Gene
https://www.readbyqxmd.com/read/29155216/communication-between-genomic-and-non-genomic-signaling-events-coordinate-steroid-hormone-actions
#11
Sandi R Wilkenfeld, Chenchu Lin, Daniel E Frigo
Steroid hormones are lipophilic molecules produced in one cell that can travel great distances within the body to elicit biological effects in another cell. In the canonical pathway, steroid hormone binding to a nuclear receptor (NR), often in the cytoplasm, causes the receptor to undergo a conformational change and translocate to the nucleus, where it interacts with specific sequences of DNA to regulate transcription. In addition to the classical genomic mechanism of action, alternate mechanisms of steroid activity have emerged that involve rapid, non-genomic signaling...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29155215/membrane-estrogen-receptors-signal-to-determine-transcription-factor-function
#12
Ellis R Levin
Estrogen receptors (ER) alpha and beta as well as many other steroid receptors are found both within the nucleus and outside the nucleus. This includes extra-nuclear receptors in many organelles, including mitochondria, endoplasmic reticulum, cytosolic endosomes, and membrane lipid rafts, such as caveolae. The functions of these receptors in the various extra-nuclear cell organelles are not well described, but progress for understanding steroid receptor signaling from the membrane has advanced. In this Review I will discuss the enlarging role of membrane ER signaling to the expression, cell localization, and function of transcription factors that are essential to mediate cell physiology or pathophysiology in many organs...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29155039/perinatal-nicotine-exposure-increases-obesity-susceptibility-by-peripheral-leptin-resistance-in-adult-female-rat-offspring
#13
Wan-Xia Zhang, Yin-Ping Li, Jie Fan, Hui-Jian Chen, Gai-Ling Li, Yan-Qiong Ouyang, You-E Yan
Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females...
November 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29154799/integrative-omics-data-analyses-of-repeated-dose-toxicity-of-valproic-acid-in-vitro-reveal-new-mechanisms-of-steatosis-induction
#14
Simone G J van Breda, Sandra M H Claessen, Marcel van Herwijnen, Daniël H J Theunissen, Danyel G J Jennen, Theo M C M de Kok, Jos C S Kleinjans
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug probably by its HCAC inhibiting properties, which may cause steatosis in the liver. The present study investigates the effect of repetitive VPA treatment of primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of VPA for 5days daily which induced lipid accumulation. Part of the PHH was left untreated for 3days for studying the persistence of 'omics' changes...
November 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29154757/macrophage-polarization-and-meta-inflammation
#15
REVIEW
Chuan Li, Maria M Xu, Kepeng Wang, Adam J Adler, Anthony T Vella, Beiyan Zhou
Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator-activated receptor gamma, the CCAAT-enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors...
November 3, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29154500/structure-activity-studies-of-peptidomimetics-based-on-kinase-inhibitory-region-of-suppressors-of-cytokine-signaling-1
#16
Sara La Manna, Laura Lopez-Sanz, Marilisa Leone, Paola Brandi, Pasqualina Liana Scognamiglio, Giancarlo Morelli, Ettore Novellino, Carmen Gomez-Guerrero, Daniela Marasco
Suppressors of Cytokine Signaling (SOCS) proteins are negative regulators of JAK proteins that are receptor-associated tyrosine kinases, which play key roles in the phosphorylation and subsequent activation of several transcription factors named STATs. Unlike the other SOCS proteins, SOCS1 and 3 show, in the N-terminal portion, a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Drug discovery processes of compounds based on KIR sequence demonstrated promising in functional in vitro and in inflammatory animal models and we recently developed a peptidomimetic called PS5, as lead compound...
November 20, 2017: Biopolymers
https://www.readbyqxmd.com/read/29154288/patterns-of-calcium-signaling-a-link-between-chronic-emotions-and-cancer
#17
Massimo Pregnolato, Giuseppe Damiani, Alfredo Pereira
Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of these phenomena suggesting their involvement in chronic emotional patterns and in the pathology of cancer. Recent developments on biophysics, translational biology and psychoneuroendocrinoimmunology (PNEI) can support explanatory hypotheses about the link between emotional stresses and the origin and development of different types of tumor cells...
November 13, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/29154209/external-signals-regulate-germinal-center-fate-determining-transcription-factors-in-the-a20-lymphoma-cell-line
#18
Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29153843/aberrant-activation-of-a-gastrointestinal-transcriptional-circuit-in-prostate-cancer-mediates-castration-resistance
#19
Shipra Shukla, Joanna Cyrta, Devan A Murphy, Edward G Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W P Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P Koche, Anuradha Gopalan, Deyou Zheng, Mark A Rubin, Howard I Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A...
November 3, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29153704/multiprotein-complexes-governing-wnt-signal-transduction
#20
REVIEW
Melissa Gammons, Mariann Bienz
Three multiprotein complexes have key roles in transducing Wnt signals from the plasma membrane to the cell nucleus - the β-catenin destruction complex, or Axin degradasome, which targets the Wnt effector β-catenin for proteasomal degradation in the absence of Wnt; the Wnt signalosome, assembled by polymerization of Dishevelled upon Wnt engaging its receptors, to inactivate the Axin degradasome, which allows β-catenin to accumulate; and the Wnt enhanceosome which enables β-catenin to gain access to target genes, to relieve their transcriptional repression by Groucho/TLE...
November 15, 2017: Current Opinion in Cell Biology
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