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Modeling gene regulation

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https://www.readbyqxmd.com/read/29031207/microrna-25-inhibits-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-pten-akt-pathway
#1
Huicong Li, Xiaoguang Zhu, Junwei Zhang, Jun Shi
Diabetic nephropathy (DN) has become the major cause of end-stage renal disease (ESRD). It has been demonstrated that apoptosis of renal tubular epithelial cells induced by hyperglycemia contributes to the pathogenesis of DN. Recent researches have corroborated the critical roles of microRNAs (miRNAs) in the apoptosis of various types of cells including renal tubular epithelial cells. However, the eff ; ;ect of miRNAs on the hyperglycemia-induced apoptosis of renal tubular epithelial cells remains unclear...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29031199/artesunate-attenuates-aclt-induced-osteoarthritis-by-suppressing-osteoclastogenesis-and-aberrant-angiogenesis
#2
Chengjin Zhao, Qingbai Liu, Kunzheng Wang
Artesunate (ART) is a semi-synthetic derivative of artemisinin and used preferentially in treatment of malaria in China. ART has strong anti-inflammatory, anti-tumor, and anti-angiogenic properties. Although the pharmacological effect of ART in osteoarthritis (OA) is unknown, evidence suggests that ART might regulate osteoclastogenesis through NF-κB signaling. In this study we explored the therapeutic effect of ART in an anterior cruciate ligament transection (ACLT)-induced OA model. We found that ART effectively relieved ACLT-induced osteoarthritis, as demonstrated by the improvement expression of pathological genes...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29029321/rapid-novel-facile-biosynthesized-silver-nanoparticles-from-bacterial-release-induce-biogenicity-and-concentration-dependent-in-vivo-cytotoxicity-with-embryonic-zebrafish-a-mechanistic-insight
#3
Suresh K Verma, Ealisha Jha, Pritam Kumar Panda, Anurag Mishra, Arun Thirumurugan, Biswadeep Das, S K S Parashar, Mrutyunjay Suar
In this study, rapid one step facile synthesis of silver nanoparticles (AgNP) was done using culture supernatant of two Gram positive (B.thuringiensis, S.aureus) and Gram negative (E.coli, S.typhimurium) bacterial strains and were termed as "BTAgNP", "SAAgNP", "ECAgNP" and "STAgNP" respectively. Synthesized AgNPs were well characterized with the help of different standard techniques like FESEM, DLS, UV-Vis spectroscopy and FTIR. Mechanism of AgNPs synthesis was elucidated using in silico approach. In vivo cytotoxicity of synthesized AgNPs was assessed in embryonic Zebrafish model with the help of uptake, oxidative stress and apoptosis induction experimental assays and the mechanism was investigated through in silico approach at the molecular level...
September 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29029263/role-of-stat3-in-skin-fibrosis-and-transforming-growth-factor-beta-signalling
#4
Mesias Pedroza, Sarah To, Shervin Assassi, Minghua Wu, David Tweardy, Sandeep K Agarwal
Objective: SSc is an autoimmune disease characterized by progressive fibrosis of the skin and internal organs. IL-6 and related cytokines that signal through STAT3 have been implicated in the pathogenesis of SSc and mouse models of fibrosis. The aim of this study was to investigate the efficacy of inhibiting STAT3 in the development of fibrosis in two mouse models of skin fibrosis. Methods: Biopsy samples of skin from SSc patients and healthy control subjects were used to determine the expression pattern of phosphotyrosyl (pY705)-STAT3...
September 23, 2017: Rheumatology
https://www.readbyqxmd.com/read/29029226/new-insights-into-the-genetic-basis-of-monge-s-disease-and-adaptation-to-high-altitude
#5
Tsering Stobdan, Ali Akbari, Priti Azad, Dan Zhou, Orit Poulsen, Otto Appenzeller, Gustavo F Gonzales, Amalio Telenti, Emily H M Wong, Shubham Saini, Ewen F Kirkness, J Craig Venter, Vineet Bafna, Gabriel G Haddad
Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology and molecular mechanisms that underlie long-term exposure to hypoxia. Here we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and non-CMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the non-carriers and accordingly prioritize genes associated with the CMS or non-CMS phenotype...
September 19, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29029225/glucocorticoid-signaling-in-health-and-disease-insights-from-tissue-specific-gr-knockout-mice
#6
Shannon Whirledge, Donald B DeFranco
Glucocorticoids are adrenally produced hormones critically involved in development, general physiology, and control of inflammation. Since their discovery, glucocorticoids have been widely utilized to treat a variety of inflammatory conditions. However, high doses or prolonged use leads to a number of side-effects throughout the body, which preclude their clinical utility. The primary actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), a transcription factor that regulates many complex signaling pathways...
October 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/29029116/upregulation-of-irs1-enhances-igf1-response-in-y537s-and-d538g-esr1-mutant-breast-cancer-cells
#7
Zheqi Li, Kevin M Levine, Amir Bahreini, Peilu Wang, David Chu, Ben Ho Park, Steffi Oesterreich, Adrian V Lee
Increased evidence suggests that somatic mutations in the ligand binding domain of estrogen receptor (ERα/ESR1) are critical mediators of endocrine-resistant breast cancer progression. Insulin-like growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis, and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29029094/thyroid-hormone-metabolism-defects-in-a-mouse-model-of-sbp2-deficiency
#8
Jiao Fu, Haruki Fujisawa, Benjamin Follman, Xiao-Hui Liao, Alexandra M Dumitrescu
SBP2 (selenocysteine insertion sequence binding protein 2) is an essential factor in selenoprotein synthesis. Patients with SBP2 defects have a characteristic thyroid phenotype and additional manifestations such as growth delay, male infertility, impaired motor coordination and developmental delay. The thyroid phenotype has become pathognomonic for this defect and putative deficiencies in the iodothyronine deiodinases selenoenzymes have been implicated. To investigate the role of SBP2 and selenoproteins in thyroid physiology and answer questions raised by the human syndrome we generated a tamoxifen inducible Sbp2 conditional knockout (iCKO) mouse model...
September 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29028988/quasar-mpra-accurate-allele-specific-analysis-for-massively-parallel-reporter-assays
#9
Cynthia A Kalita, Gregory A Moyerbrailean, Christopher Brown, Xiaoquan Wen, Francesca Luca, Roger Pique-Regi
Motivation: The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRA), have been used to functionally validate non-coding variants...
September 22, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29028486/a-point-mutation-in-the-extracellular-domain-of-cd4-completely-abolishes-cd4-t-cell-development-in-c57bl-6-mouse
#10
Huijie Wang, Saichao Li, Tianzhu Chao, Xugang Wang, Lijin Shi, Lichen Zhang, Yinming Liang, Qianqian Zheng, Liaoxun Lu
In this study, we performed ENU mutagenesis and multi-parameter flow cytometric analysis in C57BL/6 mice to uncover novel genes or alleles regulating immune cell development. We identified a novel mutant allele of Cd4 gene which completely blocked development of a major subset of T cells named CD4 T cell. Our data for the first time showed experimentally in mice the critical role of the first extracellular domain, by obtaining mice with a loss of function mutation from Ile to Asn at the position 99 of CD4 (I99N)...
October 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29028222/role-of-rbp2-induced-er-and-igf1r-erbb-signaling-in-tamoxifen-resistance-in-breast-cancer
#11
Hee-Joo Choi, Hyeong-Seok Joo, Hee-Young Won, Kyueng-Whan Min, Hyung-Yong Kim, Taekwon Son, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong
Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764)...
April 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29028094/upregulation-of-mir-802-suppresses-gastric-cancer-oncogenicity-via-targeting-rab23-expression
#12
X-Y Zhang, J-H Mu, L-Y Liu, H-Z Zhang
OBJECTIVE: The aberrant expression of microRNAs (miRNAs) has been observed in various types of cancer. Recently, miR-802 was found to play important role in tumor progression. However, the function of miR-802 in gastric cancer (GC) remains unknown. The aim of the present study was to investigate biological effects and underlying mechanisms of miR-802 in GC. PATIENTS AND METHODS: Quantitative RT-PCR was performed to evaluate the expression level of miR-802 in GC tissues and cell lines...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29027980/the-plasticizer-bisphenol-a-perturbs-the-hepatic-epigenome-a-systems-level-analysis-of-the-mirnome
#13
Ludivine Renaud, Willian A da Silveira, E Starr Hazard, Jonathan Simpson, Silvia Falcinelli, Dongjun Chung, Oliana Carnevali, Gary Hardiman
Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29027943/low-grade-dysplastic-nodules-revealed-as-the-tipping-point-during-multistep-hepatocarcinogenesis-by-dynamic-network-biomarkers
#14
Lina Lu, Zhonglin Jiang, Yulin Dai, Luonan Chen
Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem is to identify when and how the critical transition happens during the HCC initiation period at a molecular level. In this work, for the first time, we revealed that LGDNs is the tipping point (i...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29027433/-inhibitory-mechanisms-of-timosaponin-a%C3%A2-on-proliferation-and-growth-of-human-glioblastoma-cells
#15
Xi Tan, Hui-Jun Pan, Wei-da Wu, Dan-Dan Zhang
To explore the inhibitory effect of timosaponin AⅢ on the proliferation of human glioblastoma cell line U87MG and investigate its related mechanism. As compared with the model group, the tumor weight was significantly reduced in timosaponin AⅢ-treated group. Timosaponin AⅢinhibited the proliferation of U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein expression levels of p21, meanwhile inhibited the protein expression levels of β-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of β-Catenin into nucleus, suppressed the phosphorylation expression of ERK, but increased the phosphorylation expression of p38 and JNK...
March 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29027174/mobe-chip-probing-cell-type-specific-binding-through-large-scale-chromatin-immunoprecipitation
#16
Shenqi Wang, On Sun Lau
In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29027124/tak1-inhibition-ameliorates-survival-from-graft-versus-host-disease-in-an-allogeneic-murine-marrow-transplantation-model
#17
Ayako Kobayashi, Shinichi Kobayashi, Kosuke Miyai, Yukiko Osawa, Toshikatsu Horiuchi, Shoichiro Kato, Takaaki Maekawa, Takeshi Yamamura, Junichi Watanabe, Ken Sato, Hitoshi Tsuda, Fumihiko Kimura
Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT). Majority of the current immunosuppressive strategies targeting donor T cells to prevent or treat acute GVHD are only partially effective, and often require escalated immunosuppressive therapy. Recent studies have revealed that activation of antigen-presenting cells in the proinflammatory milieu is important for the priming and promotion of GVHD. This activation is mediated by innate immune signaling pathways, which therefore potentially represent new targets in addressing GVHD...
October 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29027056/curcumin-affords-neuroprotection-and-inhibits-%C3%AE-synuclein-aggregation-in-lipopolysaccharide-induced-parkinson-s-disease-model
#18
Neha Sharma, Bimla Nehru
Parkinson's disease (PD) pathology is characterized by the abnormal accumulation and aggregation of the pre-synaptic protein α-synuclein in the dopaminergic neurons as Lewy bodies (LBs). Curcumin, which plays a neuroprotective role in various animal models of PD, was found to directly modulate the aggregation of α-synuclein in in vitro as well as in in vivo studies. While curcumin has been shown to exhibit strong anti-oxidant and anti-inflammatory properties, there are a number of other possible mechanisms by which curcumin may alter α-synuclein aggregation which still remains obscure...
October 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29026441/modeling-the-architecture-of-the-regulatory-system-controlling-methylenomycin-production-in-streptomyces-coelicolor
#19
Jack E Bowyer, Emmanuel Lc de Los Santos, Kathryn M Styles, Alex Fullwood, Christophe Corre, Declan G Bates
BACKGROUND: The antibiotic methylenomycin A is produced naturally by Streptomyces coelicolor A3(2), a model organism for streptomycetes. This compound is of particular interest to synthetic biologists because all of the associated biosynthetic, regulatory and resistance genes are located on a single cluster on the SCP1 plasmid, making the entire module easily transferable between different bacterial strains. Understanding further the regulation and biosynthesis of the methylenomycin producing gene cluster could assist in the identification of motifs that can be exploited in synthetic regulatory systems for the rational engineering of novel natural products and antibiotics...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29026434/a-plant-based-chemical-genomics-screen-for-the-identification-of-flowering-inducers
#20
Martijn Fiers, Jorin Hoogenboom, Alice Brunazzi, Tom Wennekes, Gerco C Angenent, Richard G H Immink
BACKGROUND: Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study...
2017: Plant Methods
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