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https://www.readbyqxmd.com/read/29245068/overexpression-of-microrna-375-impedes-platelet-derived-growth-factor-induced-proliferation-and-migration-of-human-fetal-airway-smooth-muscle-cells-by-targeting-janus-kinase-2
#1
Yamei Ji, Xin Yang, Huixia Su
The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF...
December 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29245047/polyriboinosinic-polyribocytidylic-acid-facilitates-interleukin-6-and-interleukin-8-secretion-in-human-dermal-fibroblasts-via-the-jak-stat3-and-p38-mapk-signal-transduction-pathways
#2
Zhang Ying Zhu, Cong Zhuo Jia, Jian Min Luo, Li Wang
Polyriboinosinic-polyribocytidylic acid (polyI:C) is a viral dsRNA analoguethat promotes wounds healing, accelerates re-epithelialization, granulation and neovascularization, and induces pro-inflammatory cytokine release. Little is known about polyI:C mediated induction of inflammatory mediators in human dermal fibroblast (HDFs), which form the primary scaffold for epithelial cells covering the wound. Here, we found that polyI:C enhances IL-6 and IL-8 mRNA expression and induces of IL-6 and IL-8 production in a concentration-dependent and time-dependent manner in HDFs...
December 12, 2017: Cytokine
https://www.readbyqxmd.com/read/29244196/iron-overload-induces-g1-phase-arrest-and-autophagy-in-murine-preosteoblast-cells
#3
Wan-Jing Cen, Yi Feng, Shu-Shu Li, Wei-Liang Huang, Tao Zhang, Wu Zhang, Wei-Dong Kong, Jian-Wei Jiang
This study aimed to investigate the cell cycle arrest and autophagy induced by iron overload inMC3T3-E1 cells. MC3T3-E1 cells were cultured in different concentrations of ferric ammonium citrate (FAC), and Perls' Prussian blue reaction was used to detect the iron levels of the cells. CCK-8 assays were used to detect the growth of MC3T3-E1. The level of reactive oxygen species (ROS) within cells was investigated with DCFH-DA. PI staining was used to analyze the cell cycle distribution of MC3T3-E1 cells. Finally, the expression levels of cell cycle related proteins, autophagy related proteins, AKT, p38 MAPK, Stat3 and their downstream proteins were detected with western blot assays...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29244194/arid5a-stabilizes-ox40-mrna-in-murine-cd4-t-cells-by-recognizing-a-stem-loop-structure-in-its-3-utr
#4
Hamza Hanieh, Kazuya Masuda, Hozaifa Metwally, Jaya P Chalise, Maged Mohamed, Kishan K Nyati, Daron M Standley, Songling Li, Mitsuru Higa, Mohammad M Zaman, Tadamitsu Kishimoto
AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remains unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4+ T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation...
December 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#5
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29242509/shp2-associates-with-nuclear-localization-of-stat3-significance-in-progression-and-prognosis-of-colorectal-cancer
#6
Yan Huang, Jie Wang, Fuao Cao, Hailong Jiang, An Li, Jianzhong Li, Lei Qiu, Hao Shen, Wenjun Chang, Chuanxiang Zhou, Yamin Pan, Yiming Lu
Tyrosine phosphatase SHP2, encoded by PTPN11, has been implicated in many physiologic and pathologic processes in neoplastic progression. However, controversies are emerging from many studies, indicating SHP2 has a dual role in different types of tumors. We aimed to explore the role of SHP2 in progression and prognosis of colorectal cancer (CRC). SHP2 inhibited CRC cell proliferation and migration, and the phosphorylation of STAT3 was negatively regulated by SHP2 in CRC. SHP2 and nuclear STAT3 were examined in 270 CRC tissues...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29242170/a-shift-in-the-il-6-stat3-signalling-pathway-imbalance-towards-the-shp2-pathway-in-severe-asthma-results-in-reduced-proliferation-process
#7
Ikhlass Haj Salem, Sophie Plante, Abdelilah S Gounni, Mahmoud Rouabhia, Jamila Chakir
BACKGROUND: Bronchial fibroblasts are the main structural cells responsible for extracellular matrix production and turnover in lung tissue. They play a key role in airway remodelling in asthma through different cytokines including interleukin (IL-6). OBJECTIVE: To decipher IL-6 signalling in bronchial fibroblasts obtained from severe eosinophilic asthmatics compared to mild asthmatics and healthy controls. METHODS: Human bronchial fibroblasts were isolated from bronchial biopsies of mild and severe eosinophilic asthmatics and non-atopic healthy controls...
December 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29238204/low-expression-of-dab2ip-predicts-an-unfavorable-prognosis-in-human-bladder-carcinoma
#8
Linfeng Zheng, Kaiyan Chen, Liang Zhu, Dan Su, Guoping Cheng
The DOC-2/DAB2 interactive protein (DAB2IP) is a novel member of the Ras GTPase-activating protein family, and its downregulation is an unfavorable prognostic factor in several human malignancies. In this study, we retrospectively analyzed clinicopathological features, outcomes, and DAB2IP expression in 77 patients with urothelial carcinoma of the bladder (UCB). Expression of DAB2IP and p-STAT3 was examined in tumors and in matched adjacent non-cancerous tissues, using immunohistochemistry. We found a marked reduction in the expression of DAB2IP in UCB specimens, which was significantly associated with advanced pathological stage (P=0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29238104/indole-3-propionic-acid-suppresses-indoxyl-sulfate-induced-expression-of-fibrotic-and-inflammatory-genes-in-proximal-tubular-cells
#9
Maimaiti Yisireyili, Kyosuke Takeshita, Shinichi Saito, Toyoaki Murohara, Toshimitsu Niwa
Indoxyl sulfate (IS) induces fibrosis and inflammation in kidneys via oxidative stress through the induction of transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein-1 (MCP-1). Furthermore, IS is a potent endogenous agonist for aryl hydrocarbon receptor (AHR), which regulates the transcription of genes such as cytochrome P450 (CYP) 1A1. Indole-3-propionic acid (IPA) is an antioxidant and has been reported to be neuroprotective. We determined whether IPA suppresses IS-induced expression of AHR, CYP1A1, TGF-β1, and MCP-1 in proximal tubular cells...
November 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/29237840/human-cytomegalovirus-ul111a-and-us27-gene-products-enhance-the-cxcl12-cxcr4-signaling-axis-via-distinct-mechanisms
#10
Carolyn C Tu, Kathleen L Arnolds, Christine M O'Connor, Juliet V Spencer
Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects. We found that cmvIL-10 increased signaling outcomes from human CXCR4, a chemokine receptor with essential roles in hematopoiesis and immune cell trafficking, in response to its natural ligand CXCL12...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29237593/identification-of-novel-recurrent-stat3-rara-fusions-in-acute-promyelocytic-leukemia-lacking-t-15-17-q22-q12-pml-rara
#11
Li Yao, Lijun Wen, Nana Wang, Tianhui Liu, Yang Xu, Changgeng Ruan, Depei Wu, Suning Chen
No abstract text is available yet for this article.
December 13, 2017: Blood
https://www.readbyqxmd.com/read/29237553/the-snp-rs4252548-r112h-which-is-associated-with-reduced-human-height-compromises-the-stability-of-il-11
#12
Juliane Lokau, Sascha Göttert, Philipp Arnold, Stefan Düsterhöft, David Massa López, Joachim Grötzinger, Christoph Garbers
Height is a complex human phenotype that is influenced by variations in a high number of genes. Recently, a single nucleotide polymorphism (SNP) within IL11 (rs4252548) has been described to be associated with height in adults of European ancestry. This coding SNP leads to the exchange of Arg-112 to His-112 within the cytokine Interleukin-11 (IL-11), which has a well-established role in osteoclast development and bone turnover. The functional consequences of the R112H mutation are unknown so far. In this study, we show by molecular replacement that Arg-112 does not participate in binding of IL-11 to its receptors IL-11R and glycoprotein 130 (gp130)...
December 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29237164/mir-124-inhibits-growth-and-enhances-radiation-induced-apoptosis-in-non-small-cell-lung-cancer-by-inhibiting-stat3
#13
Mengjie Wang, Bi Meng, Yangchen Liu, Jingwen Yu, Qiaoyun Chen, Yangchen Liu
BACKGROUND/AIMS: A growing body of evidence indicates that the abnormal expression of microRNAs (miRNAs) play an important role in sensitizing the cellular response to ionizing radiation (IR). The aim of this study was to investigate whether the expression of miR-124 correlated with radiosensitivity in the context of non-small-cell lung carcinoma (NSCLC). METHODS: Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-124 expression in NSCLC tissues and cell lines...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29236318/proliferation-and-apoptosis-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-following-signal-transducer-and-activator-of-transcription-3-rna-interference-delivery
#14
Xuehui Sun, Yun Han, Ying Liu, Yanchun Tang, Jibo Wang
OBJECTIVE: In this study, we investigated the effects of delivering small interfering RNA (siRNA) for efficient STAT3 downregulation on propagation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). METHODS: The FLSs were transfected with three different siRNAs. RNAi-1 was selected for further experiments. The expression levels of both STAT3 mRNA and its protein were detected by RT-PCR and western blot. The proliferation of FLSs was examined by MTT assay...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235481/targeted-inhibition-of-stat-tet1-axis-as-a-therapeutic-strategy-for-acute-myeloid-leukemia
#15
Xi Jiang, Chao Hu, Kyle Ferchen, Ji Nie, Xiaolong Cui, Chih-Hong Chen, Liting Cheng, Zhixiang Zuo, William Seibel, Chunjiang He, Yixuan Tang, Jennifer R Skibbe, Mark Wunderlich, William C Reinhold, Lei Dong, Chao Shen, Stephen Arnovitz, Bryan Ulrich, Jiuwei Lu, Hengyou Weng, Rui Su, Huilin Huang, Yungui Wang, Chenying Li, Xi Qin, James Mulloy, Yi Zheng, Jiajie Diao, Jie Jin, Chong Li, Paul P Liu, Chuan He, Yuan Chen, Jianjun Chen
Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29234590/an-integrative-analysis-of-dna-methylation-in-osteosarcoma
#16
Jie Xu, Deng Li, Zhiqing Cai, Yingbin Zhang, Yulin Huang, Baohua Su, Ruofan Ma
Background: The study aimed to analyze aberrantly methylated genes, relevant pathways and transcription factors (TFs) in osteosarcoma (OS) development. Methods: Based on the DNA methylation microarray data GSE36002 that were downloaded from GEO database, the differentially methylated genes in promoter regions were identified between OS and normal samples. Pathway and function enrichment analyses of differentially methylated genes was performed. Subsequently, protein-protein interaction (PPI) network was constructed, followed by identification of cancer-associated differentially methylated genes and significant differentially methylated TFs...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29234527/sphingosine-1-phosphate-receptor-1-modulates-cntf-induced-axonal-growth-and-neuroprotection-in-the-mouse-visual-system
#17
Sandrine Joly, Deniz Dalkara, Vincent Pernet
The lack of axonal regeneration and neuronal cell death causes permanent neurological deficits in the injured CNS. Using the classical CNS injury model of optic nerve crush in mice, ciliary neurotrophic factor (CNTF) was found to stimulate retinal ganglion cell (RGC) survival and axonal growth, but in an incomplete fashion. The elucidation of molecular mechanisms impairing CNTF-induced axonal regeneration is paramount to promote visual recovery. In the present study, we sought to evaluate the contribution of sphingosine 1-phosphate receptor 1 (S1PR1) to the neuroprotective and regenerative effects of CNTF...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29234062/development-of-erasin-a-chromone-based-stat3-inhibitor-which-induces-apoptosis-in-erlotinib-resistant-lung-cancer-cells
#18
Christian Lis, Stefan Rubner, Martin Roatsch, Angela Berg, Tyler Gilcrest, Darwin Fu, Elizabeth Nguyen, Anne-Marie Schmidt, Harald Krautscheid, Jens Meiler, Thorsten Berg
Inhibition of protein-protein interactions by small molecules offers tremendous opportunities for basic research and drug development. One of the fundamental challenges of this research field is the broad lack of available lead structures from nature. Here, we demonstrate that modifications of a chromone-based inhibitor of the Src homology 2 (SH2) domain of the transcription factor STAT5 confer inhibitory activity against STAT3. The binding mode of the most potent STAT3 inhibitor Erasin was analyzed by the investigation of structure-activity relationships, which was facilitated by chemical synthesis and biochemical activity analysis, in combination with molecular docking studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233935/ligand-dependent-interaction-of-ppar%C3%AE-with-t-cell-protein-tyrosine-phosphatase-45-enhances-insulin-signaling
#19
Taesik Yoo, Sun Ah Ham, Won Jin Lee, Seon In Hwang, Jin-A Park, Jung Seok Hwang, Jinwoo Hur, Ho-Chul Shin, Sung Gu Han, Chi-Ho Lee, Dong Wook Han, Kyung Shin Paek, Han Geuk Seo
Peroxisome proliferator-activated receptor (PPAR) δ plays a pivotal role in metabolic homeostasis through its effect on insulin signaling. Although diverse genomic actions of PPARδ are postulated, the specific molecular mechanisms whereby PPARδ controls insulin signaling have not been fully elucidated. We demonstrate here that short-term activation of PPARδ results in formation of a stable complex with nuclear T cell protein tyrosine phosphatase 45 (TCPTP45) isoform. This interaction of PPARδ with TCPTP45 blocked translocation of TCPTP45 into the cytoplasm, thereby preventing its interaction with the insulin receptor, which inhibits insulin signaling...
December 12, 2017: Diabetes
https://www.readbyqxmd.com/read/29233790/preclinical-evidence-for-combined-use-of-aromatase-inhibitors-and-nsaids-as-preventive-agents-of-tobacco-induced-lung-cancer
#20
Laura P Stabile, Mariya Farooqui, Beatriz Kanterewicz, Shira Abberbock, Brenda F Kurland, Brenda Diergaarde, Jill M Siegfried
INTRODUCTION: A hormonal role in non-small cell lung cancer (NSCLC) development is well documented. We previously showed that the aromatase inhibitor (AI) anastrozole decreased the development of tobacco carcinogen-induced lung tumors in a murine lung cancer prevention model and that aromatase and estrogen receptor (ER) were expressed in pulmonary inflammatory cells. METHODS: We utilized a tobacco carcinogen-induced lung tumor mouse model [4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)] to determine whether an AI combined with non-steroidal anti-inflammatory drugs (NSAIDs) results in greater lung tumor prevention effects than single agent treatment...
December 9, 2017: Journal of Thoracic Oncology
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