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https://www.readbyqxmd.com/read/28820735/the-use-of-sirna-as-a-pharmacological-tool-to-assess-a-role-for-the-transcription-factor-nf-il6-in-the-brain-under-in-vitro-and-in-vivo-conditions-during-lps-induced-inflammatory-stimulation
#1
Jelena Damm, Joachim Roth, Rüdiger Gerstberger, Christoph Rummel
BACKGROUND: Studies with NF-IL6-deficient mice indicate that this transcription factor plays a dual role during systemic inflammation with pro- and anti-inflammatory capacities. Here, we aimed to characterize the role of NF-IL6 specifically within the brain. METHODS: In this study, we tested the capacity of short interfering (si) RNA to silence the inflammatory transcription factor nuclear factor-interleukin 6 (NF-IL6) in brain cells under in vitro and in vivo conditions...
August 18, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28820502/oligonucleotides-targeting-periostin-ameliorates-pulmonary-fibrosis
#2
A Tomaru, T Kobayashi, J A Hinneh, P B Tonto, C N D' Alessandro-Gabazza, H Fujimoto, K Fujiwara, Y Takahashi, M Ohnishi, T Yasuma, K Nishihama, M Yoshino, K Takao, M Toda, T Totoki, Y Takei, K Yoshikawa, O Taguchi, E C Gabazza
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3 to 4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here, we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibit lung fibrosis by direct administration into the lung by intranasal route...
August 18, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28820331/polo-like-kinase-1-plk1-dependent-phosphorylation-of-methylenetetrahydrofolate-reductase-mthfr-regulates-replication-via-histone-methylation
#3
Xueyan Li, Shanshan Nai, Yuehe Ding, Qizhi Geng, Bingtao Zhu, Kai Yu, Wei-Guo Zhu, Meng-Qiu Dong, Xiao-Dong Su, Xingzhi Xu, Jing Li
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the folate cycle and its genetic variations have been associated with various human diseases. Previously we identified that MTHFR is phosphorylated by cyclin-dependent kinase 1 (CDK1) at T34 and MTHFR underlies heterochromatin maintenance marked by H3K9me3 levels. Herein we demonstrate that pT34 creates a binding motif that docks MTHFR to the polo-binding domain (PBD) of polo-like kinase 1 (PLK1), a fundamental kinase that orchestrates many cell cycle events...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820076/a-novel-danshensu-tetramethylpyrazine-conjugate-dt-018-provides-cardioprotection-by-preserving-mitochondrial-function-through-the-mef2d-pgc-1%C3%AE-pathway
#4
Xiaojing Zhang, Jingxiong Luo, Yali Huang, Huixing Deng, Huihui Hu, Pei Yu, Yewei Sun, Luchen Shan, Yuqiang Wang
In this work, we explored the protective effect of DT-018, a danshensu and tetramethylpyrazine conjugate, on mitochondrial injury induced by tert-butylhydroperoxide (t-BHP) and its possible mechanisms of action. DT-018 effectively quenched intracellular and mitochondrial reactive oxygen species (ROS), preserved the mitochondrial function, restored the intracellular level of ATP and augmented mitochondrial membrane potential (ΔΨm) while suppressed mitochondrial swelling in isolated myocardial mitochondria...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28820065/bcg-increased-membrane-expression-of-trim59-through-the-tlr2-tlr4-irf5-pathway-in-raw264-7-macrophages
#5
Jin Zheng, Tian Yuan, Yan Dongmei, Li Dong, Zhu Xun
OBJECTIVE: In our previous study, we showed that Bacillus Calmette-Guerin (BCG)-activated macrophages have the ability to directly kill tumor cells. One of the main properties of these macrophages is the high expression of tripartite motif family protein 59 (TRIM59). This study was conducted to investigate the mechanism of BCG-induced TRIM59 expression on macrophages and to identify the subcellular localization of TRIM59. METHODS: TRIM59 expression and TNF-α secretion were compared in RAW264...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28819440/microrna-204-5p-inhibits-invasion-and-metastasis-of-laryngeal-squamous-cell-carcinoma-by-suppressing-forkhead-box-c1
#6
Wei Gao, Yongyan Wu, Xiaoling He, Chunming Zhang, Meixia Zhu, Bo Chen, Qingqing Liu, Xukuan Qu, Weiyan Li, Shuxin Wen, Binquan Wang
Background and aim: Understanding the molecular biological mechanisms underlying laryngeal squamous cell carcinoma (LSCC) invasion and metastasis is crucial for diagnosis, treatment, and prognosis. We aimed to examine the expression of the tumor suppressor microRNA-204-5p (miR-204-5p) and its target gene, forkhead box C1 (FOXC1), in human LSCC and explore their roles in the malignant behaviors of LSCC Hep-2 and TU-177 cells. Methods: The regulatory effects of miR-204-5p on the 3' untranslated region of FOXC1 predicted by bioinformatics were tested by dual-luciferase reporter assay...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819413/the-role-of-%C3%AE-catenin-in-the-initiation-and-metastasis-of-ta2-mice-spontaneous-breast-cancer
#7
Dan Zhang, Fei Fei, Shuyuan Li, Yongjie Zhao, Zhengduo Yang, Jie Qu, Xipeng Zhang, Yu Yin, Shiwu Zhang
Purpose: Tientsin Albino 2 (TA2) mice have a high incidence of spontaneous breast cancer. Tumor initiation is related to mouse mammary tumor virus (MMTV) infection. MMTV is hormonally regulated and may promote tumor formation via Wnt/β-catenin signaling pathway. This study attempts to clarify the relationship between β-catenin expression and the initiation and metastasis of spontaneous breast cancer in TA2 mice. Materials and Methods: Pathological samples illustrating the development of spontaneous breast cancer in TA2 mice were collected and the presence of virus particles was verified in the cancer tissue by electron microscope...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819407/ccr7-promote-lymph-node-metastasis-via-regulating-vegf-c-d-r3-pathway-in-lung-adenocarcinoma
#8
Jie Yu, Shaolin Tao, Pingping Hu, Ruwen Wang, Chunshu Fang, Yi Xu, Di Qi, Zhuanqin Wei, Jingge Zhang, Qunyou Tan
Lymph node metastasis is still an important issue in metastatic process of lung adenocarcinoma. C-C chemokine receptor 7 (CCR7) has been proved to be closely associated with the metastasis of lung adenocarcinoma, and the mechanism is poorly understood. In order to investigate the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma, and to explore the role of CCR7 in treating lung adenocarcinoma, 40 clinical specimens were collected to define the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818073/role-of-the-lncrna-abhd11-as1-in-the-tumorigenesis-and-progression-of-epithelial-ovarian-cancer-through-targeted-regulation-of-rhoc
#9
Dan-Dan Wu, Xi Chen, Kai-Xuan Sun, Li-Li Wang, Shuo Chen, Yang Zhao
BACKGROUND: There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis. METHODS: We examined the expression of the lncRNA ABHD11-AS1 in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS1 downregulation by small interfering RNA (siRNA) or ABHD11-AS1 overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules...
August 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28817973/the-agma1-polyamidoamine-mediates-the-efficient-delivery-of-sirna
#10
Roberta Cavalli, Luca Primo, Roberto Sessa, Giulia Chiaverina, Laura di Blasio, Jenny Alongi, Amedea Manfredi, Elisabetta Ranucci, Paolo Ferruti
AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1-5 polyplexes were larger, about 100 nm in size. AGMA1-10 polyplexes, but not AGMA1-5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects...
August 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28817830/microrna-200a-inhibits-transforming-growth-factor-%C3%AE-1-induced-proximal-tubular-epithelial-mesenchymal-transition-by-targeting-%C3%AE-catenin
#11
Yi Gong, Zhexue Qin, Baoshang Zhou, Hua Chen, Zhengmin Shi, Jing Zhang
BACKGROUND: The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin...
August 18, 2017: Nephron
https://www.readbyqxmd.com/read/28817677/abnormal-expression-of-nrf2-may-play-an-important-role-in-the-pathogenesis-and-development-of-adenomyosis
#12
Ning Chen, Baoying Du, Hao Zhou, Fengxian Shen, Juan Li, Zhenwei Xie
OBJECTIVE: To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis. METHODS: Western blot, immunohistochemistry(IHC) and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism. RESULTS: Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods...
2017: PloS One
https://www.readbyqxmd.com/read/28817661/ouabain-affects-cell-migration-via-na-k-atpase-p130cas-and-via-nucleus-centrosome-association
#13
Young Ou, Chen Xuan Pan, Jeremy Zuo, Frans A van der Hoorn
Na,K-ATPase is a membrane protein that catalyzes ATP to maintain transmembrane sodium and potassium gradients. In addition, Na,K-ATPase also acts as a signal-transducing receptor for cardiotonic steroids such as ouabain and activates a number of signalling pathways. Several studies report that ouabain affects cell migration. Here we used ouabain at concentrations far below those required to block Na,K-ATPase pump activity and show that it significantly reduced RPE cell migration through two mechanisms. It causes dephosphorylation of a 130 kD protein, which we identify as p130cas...
2017: PloS One
https://www.readbyqxmd.com/read/28817550/role-of-microrna-93-i-in-pathogenesis-of-left-ventricular-remodeling-via-targeting-cyclin-d1
#14
Jingjing Zhang, Li Qin, Ling Han, Ying Zhao, Hongfeng Jing, Wei Song, Haili Shi
BACKGROUND The objective of this study was to identify the pathway responsible for ventricular remodeling. MATERIAL AND METHODS We collected remodeling myocardium tissue (n=18) and control myocardium tissue (n=22), and detected the expression of 4 miRNAs in these 2 groups using real-time PCR. We then searched the miRNA database online to find the candidate genes of miR-93. Real-time PCR and Western blot analysis were used to confirm the regulatory relationship. RESULTS We found that only miR-93 was decreased in remodeling myocardium tissue, and validated CCND1 to be the direct target gene of miR-93, with the "seed sequence" located within the 3'-UTR of the target gene via luciferase reporter assay system...
August 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#15
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28816543/mir-541-5p-regulates-lung-fibrosis-by-targeting-cyclic-nucleotide-phosphodiesterase-1a
#16
Liqin Ren, Chunyan Yang, Yongfeng Dou, Renhui Zhan, Yi Sun, Yan Yu
AIM OF THE STUDY: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. MATERIALS AND METHODS: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation...
August 17, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28816418/hypoxia-induced-microrna-26b-inhibition-contributes-to-hypoxic-pulmonary-hypertension-via-ctgf
#17
Sijing Zhou, Li Sun, Chao Cao, Peipei Wu, Min Li, Gengyun Sun, Guanghe Fei, Xing Ding, Ran Wang
The objective of this study was to explore the role of miRNAs in the control of HPH as well as molecular mechanism underlying. Computational analysis and luciferase assay were carried out to search the target gene of miR-26b. Luciferase assay, RT-PCR and western-blot analysis was performed to test interaction among hypoxia, miR-26b, SRF and CTGF. MiR-26b was significantly downregulated; meanwhile, CTGF and SRF were significantly upregulated in HPH rat model. Using computational analysis, CTGF was found to be a virtual target gene of miR-26b, and only cell transfected with vectors containing wild-type CTGF 3'UTR and miR-26b showed a lower luciferase activity than scramble control...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815701/lincrna-dyn-lrb2-2-upregulates-cholesterol-efflux-by-decreasing-tlr2-expression-in-macrophages
#18
Yongqiang Li, Shuxin Shen, Shoukun Ding, Lixia Wang
OBJECTIVE: This study is designed to determine whether lincRNA-DYNLRB2-2 could promote cholesterol efflux through regulating the expression of TLR2. METHODS: THP-1 and RAW264.7 cells were incubated with oxLDL for 48 h to induce the formation of foam cells, and ORO staining was performed and intracellular cholesterol contents were measured by HPLC assay. qRT-PCR and Western blotting were performed to detect mRNA and protein expression levels, respectively. Lentiviral vector LV-DYNLRB2-2 and lincRNA-DYNLRB2-2 siRNA was constructed to explore its potential role...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#19
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#20
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
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