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https://www.readbyqxmd.com/read/28107588/mitochondrial-uncoupler-exerts-a-synthetic-lethal-effect-against-%C3%AE-catenin-mutant-tumor-cells
#1
Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya Imoto
The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28106797/the-complex-relationship-between-virulence-and-antibiotic-resistance
#2
REVIEW
Meredith Schroeder, Benjamin D Brooks, Amanda E Brooks
Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e...
January 18, 2017: Genes
https://www.readbyqxmd.com/read/28105929/a-compendium-of-human-genes-regulating-feeding-behavior-and-body-weight-its-functional-characterization-and-identification-of-gwas-genes-involved-in-brain-specific-ppi-network
#3
Elena V Ignatieva, Dmitry A Afonnikov, Olga V Saik, Evgeny I Rogaev, Nikolay A Kolchanov
BACKGROUND: Obesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation. RESULTS: The compendium of genes controlling FB or BW includes 578 human genes...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28105331/opioid-system-in-l-dopa-induced-dyskinesia
#4
REVIEW
Jing Pan, Huaibin Cai
L-3, 4-Dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) is a major clinical complication in the treatment of Parkinson's disease (PD). This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration. Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID. Opioid receptors have been targeted to alleviate the dyskinesia. However, the exact role of this altered opioid activity is remains under active investigation...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28104984/role-of-mast-cell-mir-490-5p-in-irritable-bowel-syndrome
#5
Hai-Xia Ren, Fa-Can Zhang, He-Sheng Luo, Guo Zhang, Lie-Xin Liang
AIM: To determine the functional role of miR-490-5p in mast cell proliferation and apoptosis, and in the mast cell tryptase/PAR-2 signal pathway. METHODS: The 3(rd) generation of lentivirus vector systems containing enhanced green fluorescent protein (EGFP) (Ruisai Inc., Shanghai, China), which acts as a reporter gene was used to construct the mmu-miR-490-5p lentivirus expression vector pEGFP-antagomiR-490-5p, and the lentivirus vector pEGFP-negative was used as a negative control...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104575/modulation-of-proteostasis-by-transcription-factor-nrf2-and-impact-in-neurodegenerative-diseases
#6
REVIEW
Marta Pajares, Antonio Cuadrado, Ana I Rojo
Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2)...
January 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28104361/igfbp-a-novel-target-of-lung-cancer
#7
REVIEW
QiongGe Hu, Yong Zhou, Kejing Ying, Wenjing Ruan
The insulin-like growth factor-1 receptor(IGF-1R) is a central component of lung cancer signal transduction pathways. A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC). There is an urgent need for a better understanding of signaling in IGF system. Insulin-like growth factor-binding proteins(IGFBPs) function as modulators for IGF signaling through sequestration of IGFs in serum and the extracellular fluid. IGFBPs can also act as transporters or modulators for IGF action and insulin action...
January 16, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28102581/molecular-mechanisms-and-ecological-function-of-far-red-light-signalling
#8
REVIEW
David J Sheerin, Andreas Hiltbrunner
Land plants possess the ability to sense and respond to far-red light (700-760 nm), which serves as an important environmental cue. Due to the nature of far-red light, it is not absorbed by chlorophyll and thus is enriched in canopy shade, and will also penetrate deeper into soil than other visible wavelengths. Far-red light responses include regulation of seed germination, suppression of hypocotyl growth, induction of flowering, and accumulation of anthocyanins, which depend on one member of the phytochrome photoreceptor family, phytochrome A (phyA)...
January 19, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28101851/importance-of-radioactive-labelling-to-elucidate-inositol-polyphosphate-signalling
#9
REVIEW
Miranda S C Wilson, Adolfo Saiardi
Inositol polyphosphates, in their water-soluble or lipid-bound forms, represent a large and multifaceted family of signalling molecules. Some inositol polyphosphates are well recognised as defining important signal transduction pathways, as in the case of the calcium release factor Ins(1,4,5)P3, generated by receptor activation-induced hydrolysis of the lipid PtdIns(4,5)P2 by phospholipase C. The birth of inositol polyphosphate research would not have occurred without the use of radioactive phosphate tracers that enabled the discovery of the "PI response"...
February 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28101190/ror2-inhibits-the-proliferation-of-gastric-carcinoma-cells-via-activation-of-non-canonical-wnt-signaling
#10
Likun Yan, Qingguo Du, Jianfeng Yao, Ruiting Liu
Gastric carcinoma is one of the most common human cancers and has a poor prognosis. Receptor tyrosine kinase-like orphan receptor 2 (ROR2), which is a non-canonical receptor of the Wnt signaling pathway, has been reported to be deregulated in numerous types of human cancers, including gastric carcinoma. However, the exact role of ROR2 in the regulation of the malignant phenotypes of gastric carcinoma, as well as the underlying molecular mechanism, remains largely unclear. The present study demonstrated that ROR2 was recurrently downregulated in gastric carcinoma tissues, as compared with their matched adjacent normal tissues...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100771/janus-kinase-2-jak2-dissociates-hepatosteatosis-from-hepatocellular-carcinoma-in-mice
#11
Sally Yu Shi, Stephanie A Schroer, Cynthia T Luk, Min Jeong Kim, David W Dodington, Lauren Lin, Tharini Sivasubramaniyam, Erica P Cai, Shun-Yan Lu, Kay-Uwe Wagner, Richard P Bazinet, Minna Woo
Hepatocellular carcinoma (HCC) is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression of non-alcoholic fatty liver disease and the development of hepatocellular carcinoma. However, whether steatosis per se promotes liver cancer and the molecular mechanisms that control the progression in this disease spectrum remain largely elusive. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway mediates signal transduction by numerous cytokines that regulate inflammation and may contribute to hepatocarcinogenesis...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100475/effects-of-obesity-and-exercise-on-testicular-leptin-signal-transduction-and-testosterone-biosynthesis-in-male-mice
#12
Xuejie Yi, Haining Gao, Dequan Chen, Donghui Tang, Wanting Huang, Tao Li, Tie Ma, Bo Chang
To explore the role of the testicular leptin and JAK-STAT(LEP-JAK-STAT) pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet (ND) and high-fat diet (HFD) groups. After 10 weeks, mice in the HFD group were further divided randomly into obese control (OC), obese moderate-volume exercise (OME), and obese high-volume exercise (OHE) groups. Mice in the OME group were provided with 2 h/day, 6 days/week swimming exercise for 8 weeks and mice in the OHE group underwent twice the amount of daily exercise intervention as the OME group...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28099250/interleukin-36%C3%AE-induces-inflammatory-mediators-from-human-pancreatic-myofibroblasts-via-a-myd88-dependent-pathway
#13
Atsushi Nishida, Osamu Inatomi, Takehide Fujimoto, Hirotsugu Imaeda, Masaji Tani, Akira Andoh
OBJECTIVES: Interleukin 36 (IL-36) is a recently described proinflammatory cytokine, characterized by the induction of inflammatory mediators. In the present study, we investigated the biological activity and the signal transduction of IL-36α in human pancreatic myofibroblasts. METHODS: The mRNA and protein expression of inflammatory mediators was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of IL-36α and its receptor in the pancreatic tissue was evaluated using immunohistochemical technique...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28099130/epidermal-growth-factor-receptor-egfr-involvement-in-successful-growth-hormone-gh-signaling-in-gh-transduction-defect
#14
Eirini Kostopoulou, Andrea Paola Rojas-Gil, Alexia Karvela, Bessie E Spiliotis
BACKGROUND: Growth hormone (GH) transduction defect (GHTD) is a growth disorder with impaired signal transducer and activator of transcription 3 (STAT3) phosphorylation mediated by overexpression of cytokine-inducible SH2-containing protein (CIS), which causes increased growth hormone receptor (GHR) degradation. This study investigated the role of epidermal growth factor (EGF) in the restoration of normal GH signaling in GHTD. METHODS: Protein expression, cellular localization and physical contact of proteins of the GH and EGF signaling pathways were studied by Western immunoblotting, immunofluorescence and co-immunoprecipitation, respectively...
January 18, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28098899/analysis-of-gene-expression-profiles-of-non-small-cell-lung-cancer-at-different-stages-reveals-significantly-altered-biological-functions-and-candidate-genes
#15
Jin Wang, Jianxiang Song, Zhengya Gao, Xudong Huo, Yajun Zhang, Wencai Wang, Jianwei Qi, Shiying Zheng
We attempt to dissect the pathology of non-small cell lung cancer (NSCLC) patients at different stages and discover the novel candidate genes. Microarray data (GSE21933) were retrieved from the Gene Expression Omnibus database. The differential expression profiles of lung tumor tissues during different stages were analyzed. The significantly altered functions and pathways were assessed and the key nodes in a protein-protein interaction (PPI) network were screened out. Then, the coexpression gene pairs and tumor-related genes were assessed...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098432/a-multi-mitochondrial-anticancer-agent-that-selectively-kills-cancer-cells-and-overcomes-drug-resistance
#16
Yong Bo Peng, Zi Long Zhao, Teng Liu, Guo Jian Xie, Cheng Jin, Tang Gang Deng, Yang Sun, Xiong Li, Xiao Xiao Hu, Xiao Bing Zhang, Mao Ye, Wei Hong Tan
Mitochondria are double-membrane-bound organelles involved mainly in supplying cellular energy, but also play roles in signaling, cell differentiation, and cell death. Mitochondria are implicated in carcinogenesis, and therefore dozens of lethal signal transduction pathways converge on these organelles. Accordingly, mitochondria provide an alternative target for cancer management. In this study, F16, a drug that targets mitochondria, and chlorambucil (CBL), which is indicated for the treatment of selected human neoplastic diseases, were covalently linked, resulting in the synthesis of a multi-mitochondrial anticancer agent, FCBL...
January 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28098356/mechano-chemo-transduction-in-cardiac-myocytes
#17
Ye Chen-Izu, Leighton T Izu
The heart has the ability to adjust to changing mechanical loads. The Frank-Starling law and the Anrep effect describe exquisite intrinsic mechanisms the heart has for autoregulating the force of contraction to maintain cardiac output under preload and afterload. Although these mechanisms have been known for more than a century, their cellular and molecular underpinnings are still debated. How does the cardiac myocyte sense a change in preload or afterload? How does the myocyte adjust its response to compensate for such changes? In cardiac myocytes Ca(2+) is a crucial regulator of contractile force and in this review we compare and contrast recent results from different labs that address two important questions...
January 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28098310/a-computational-model-predicts-genetic-nodes-that-allow-switching-between-species-specific-responses-in-a-conserved-signaling-network
#18
Adriana T Dawes, David Wu, Karley K Mahalak, Edward M Zitnik, Natalia Kravtsova, Haiwei Su, Helen M Chamberlin
Cell signaling networks regulate a variety of developmental and physiological processes, and changes in their response to external stimuli are often implicated in disease initiation and progression. To elucidate how different responses can arise from conserved signaling networks, we have developed a mathematical model of the well-characterized Caenorhabditis vulval development network involving EGF, Wnt and Notch signaling that recapitulates biologically observed behaviors. We experimentally block a specific element of the EGF pathway (MEK), and find different behaviors in vulval development in two Caenorhabditis species, C...
January 18, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28096534/novel-therapeutic-approach-to-improve-hematopoiesis-in-low-risk-mds-by-targeting-mdscs-with-the-fc-engineered-cd33-antibody-bi-836858
#19
E A Eksioglu, X Chen, K-H Heider, B Rueter, K L McGraw, A A Basiorka, M Wei, A Burnette, P Cheng, J Lancet, R Komrokji, J Djeu, A List, S Wei
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33(+)HLA-DR(-)Lin(-), plays a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it plays an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#20
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of IRES trans-acting factor La protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
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