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https://www.readbyqxmd.com/read/29775409/transactivation-domain-of-p53-regulates-dna-repair-and-integrity-in-human-ips-cells
#1
Ramaswamy Kannappan, Saidulu Mattapally, Pooja A Wagle, Jianyi Zhang
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#2
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761313/genomewide-dna-methylation-responses-in-patients-with-%C3%AE-thalassemia-treated-with-yisui-shengxue-granules
#3
Yan-Ling Cheng, Xin-Hua Zhang, Yu-Wen Sun, Wen-Juan Wang, Jie Huang, Na-Li Chu, Su-Ping Fang, Zhi-Kui Wu
OBJECTIVE: To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. METHODS: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention...
May 3, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29754009/dietary-nitrogen-and-calcium-modulate-cyp27b1-expression-in-young-goats
#4
M R Wilkens, K Elfers, M Schmicke, G Breves, A S Muscher-Banse
In livestock, feeding a reduced nitrogen (N) diet is favored for economic and ecological reasons. Ruminants cope more easily with a reduced N diet than monogastric species. However, changes in mineral homeostasis such as a reduction in 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ) concentrations, calcium (Ca), and IGF1 levels were observed in goats kept on a reduced N diet. The decrease in 1,25-(OH)2 D3 occurred even during a simultaneous reduction in dietary N and Ca, whereas a solitary Ca reduction stimulated 1,25-(OH)2 D3 synthesis...
April 3, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29743295/defining-the-tissue-specific-roles-of-igf1-igf1r-in-regulating-metabolism-using-the-cre-loxp-system
#5
Rhonda D Kineman, Mercedes Del Rio-Moreno, André Sarmento-Cabral
It is clear that IGF1 is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function...
May 9, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29738863/porcine-igf1-synonymous-mutation-alter-gene-expression-and-protein-binding-affinity-with-igf1r
#6
Yunyun Cheng, Songcai Liu, Gang Wang, Wenzhen Wei, Shan Huang, Rui Yang, Hongwei Geng, Haoyang Li, Jie Song, Lidan Sun, Hao Yu, Linlin Hao
CONTEXT: Insulin like growth factor 1 (IGF1) is privotal in the regulation of animal growth and is a single-chain globular protein composed of B, C, A, and D regions, of which the C region is involved in maintaining high affinity binding to the IGF1 receptor (IGF1R). PURPOSE: In this study, significant expression differences between large pigs and miniature pigs were detected and only one synonymous SNP (c.258G>A) in the C region of the coding sequence of IGF1 gene was screened...
May 5, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29733873/runx1-promotes-cell-growth-in-human-t-cell-acute-lymphoblastic-leukemia-by-transcriptional-regulation-of-key-target-genes
#7
Catherine E Jenkins, Samuel Gusscott, Rachel J Wong, Olena O Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P Weng
RUNX1 is frequently mutated in T-cell acute lymphoblastic leukemia (T-ALL). The spectrum of RUNX1 mutations has led to the notion that it acts as a tumor suppressor in this context; however, other studies have placed RUNX1 along with transcription factors TAL1 and NOTCH1 as core drivers of an oncogenic transcriptional program. To reconcile these divergent roles, we knocked down RUNX1 in human T-ALL cell lines and deleted Runx1 or Cbfb in primary mouse T-cell leukemias. RUNX1 depletion consistently resulted in reduced cell proliferation and increased apoptosis...
May 4, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29731738/insulin-like-growth-factor-2-mrna-binding-protein-3-influences-sensitivity-to-anti-igf-system-agents-through-the-translational-regulation-of-igf1r
#8
Caterina Mancarella, Michela Pasello, Maria Cristina Manara, Lisa Toracchio, Evelina Fiorenza Sciandra, Piero Picci, Katia Scotlandi
Insulin-like growth factor 2 (IGF2) mRNA-binding protein 3 (IGF2BP3) is an oncofetal protein that binds RNA, thereby influencing the fate of target transcripts. IGF2BP3 is synthesized de novo in cancer, where it promotes proliferation, drug resistance, and metastasis via both IGF2-dependent and IGF2-independent mechanisms. Ewing sarcoma (ES) is a rare bone and soft tissue tumor in which the IGF system plays a pivotal role. This study aimed to investigate the effect of IGF2BP3 on the regulation of the IGF system in ES...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29730537/association-of-body-weight-gain-with-muscle-fat-and-liver-expression-levels-of-growth-hormone-receptor-insulin-like-growth-factor-i-and-beta-adrenergic-receptor-mrnas-in-steers
#9
W Zheng, X Leng, M Vinsky, C Li, H Jiang
The physiological basis of feed efficiency is unclear. Administration of GH or beta-adrenergic agonists improves feed efficiency in various animals. The objective of this study was to test the hypothesis that more efficient cattle have greater expression of GH receptor (GHR) or beta-adrenergic receptor (ADRB) mRNA in skeletal muscle, fat, and liver, the major target tissues of GH and beta-adrenergic agonists. Fifty Angus steers were fed a finishing diet for 75 d to determine residual feed intake (RFI). Carcass measures, skeletal muscle, subcutaneous fat, and liver samples were collected from the top 10 high-RFI steers and top 10 low-RFI steers at slaughter...
April 9, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29725014/clinical-and-genomic-landscape-of-gastric-cancer-with-a-mesenchymal-phenotype
#10
Sang Cheul Oh, Bo Hwa Sohn, Jae-Ho Cheong, Sang-Bae Kim, Jae Eun Lee, Ki Cheong Park, Sang Ho Lee, Jong-Lyul Park, Yun-Yong Park, Hyun-Sung Lee, Hee-Jin Jang, Eun Sung Park, Sang-Cheol Kim, Jeonghoon Heo, In-Sun Chu, You-Jin Jang, Young-Jae Mok, WonKyung Jung, Baek-Hui Kim, Aeree Kim, Jae Yong Cho, Jae Yun Lim, Yuki Hayashi, Shumei Song, Elena Elimova, Jeannelyn S Estralla, Jeffrey H Lee, Manoop S Bhutani, Yiling Lu, Wenbin Liu, Jeeyun Lee, Won Ki Kang, Sung Kim, Sung Hoon Noh, Gordon B Mills, Seon-Young Kim, Jaffer A Ajani, Ju-Seog Lee
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy...
May 3, 2018: Nature Communications
https://www.readbyqxmd.com/read/29721854/abscisic-acid-supplementation-rescues-high-fat-diet-induced-alterations-in-hippocampal-inflammation-and-irss-expression
#11
Alberto Ribes-Navarro, Mariam Atef, Sandra Sánchez-Sarasúa, María Teresa Beltrán-Bretones, Francisco Olucha-Bordonau, Ana María Sánchez-Pérez
Accumulated evidence indicates that neuroinflammation induces insulin resistance in the brain. Moreover, both processes are intimately linked to neurodegenerative disorders, including Alzheimer's disease. Potential mechanisms underlying insulin resistance include serine phosphorylation of the insulin receptor substrate (IRS) or insulin receptor (IR) misallocation. However, only a few studies have focused on IRS expression in the brain and its modulation in neuroinflammatory processes. This study used the high-fat diet (HFD) model of neuroinflammation to study the alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS expressions in the hippocampus...
May 2, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29716918/igf2-ir-igf1r-pathway-in-tumor-cells-and-myofibroblasts-mediates-resistance-to-egfr-inhibition-in-cholangiocarcinoma
#12
Javier Vaquero, Cindy Lobe, Sylvana Tahraoui, Audrey Clapéron, Martine Mergey, Fatiha Merabtene, Dominique Wendum, Cédric Coulouarn, Chantal Housset, Christèle Desbois-Mouthon, Francoise Praz, Laura Fouassier
PURPOSE: Cholangiocarcinoma (CCA) is a desmoplastic tumor of the biliary tree in which epidermal growth factor receptor (EGFR) is overexpressed and contributes to cancer progression. Although, EGFR has been envisaged as a target for therapy, treatment with tyrosine kinase inhibitors (TKI) such as erlotinib did not provide therapeutic benefit in patients with CCA, emphasizing the need to investigate resistance mechanisms against EGFR inhibition. EXPERIMENTAL DESIGN: Resistant CCA cells to EGFR inhibition were obtained upon long time exposure of cells with erlotinib...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29709726/rna-sequencing-reveals-significant-mirnas-in-atypical-endometrial-hyperplasia
#13
Shiqian Tang, Yinmei Dai
PURPOSE: In this paper, we aimed to investigate the miRNAs that played a regulatory role in the development of atypical endometrial hyperplasia (AEH). METHODS: RNA sequencing was performed for endometrial tissues from 3 AEH patients and 3 endometrial normal hyperplasia patients. RNA sequencing data were processed and differentially expressed (DE) miRNAs were identified between AEH and controls. The target genes for DE miRNAs were identified and mapped to the protein-protein interaction (PPI) network...
March 19, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29707131/gene-expression-analyses-determine-two-different-subpopulations-in-kit-negative-gist-like-kngl-patients
#14
David S Moura, Rafael Ramos, Antonio Fernandez-Serra, Teresa Serrano, Julia Cruz, Ramiro Alvarez-Alegret, Rosa Ortiz-Duran, Luis Vicioso, Maria Luisa Gomez-Dorronsoro, Xavier Garcia Del Muro, Javier Martinez-Trufero, Jordi Rubio-Casadevall, Isabel Sevilla, Nuria Lainez, Antonio Gutierrez, Cesar Serrano, Maria Lopez-Alvarez, Nadia Hindi, Miguel Taron, José Antonio López-Guerrero, Javier Martin-Broto
Introduction: There are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients. Methods: KIT , PDGFRA , DOG1 , IGF1R , MIR221 and MIR222 expression levels were determined by qRT-PCR...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29706427/effect-of-acute-stressors-adrenocorticotropic-hormone-administration-and-cortisol-release-on-milk-yield-the-expression-of-key-genes-proliferation-and-apoptosis-in-goat-mammary-epithelial-cells
#15
G F Bomfim, G K F Merighe, S A de Oliveira, J A Negrao
Cortisol is essential to milk synthesis; however, different acute stressors and the exogenous administration of adrenocorticotropic hormone (ACTH) decrease milk yield. Therefore, the effect of cortisol on milk yield and its influence on the survival of mammary epithelial cells have not been fully elucidated. In this context, the objective of this study was to evaluate the effect of cortisol on the expression of growth hormone receptor (GHR), insulin-like growth factor type 1 (IGF1), insulin-like growth factor type 1 receptor (IGF1R), insulin-like growth factor-binding protein 3 and 5 (IGFBP3 and IGFBP5), BAX, and BCL2 genes on the proliferation and apoptotic rates of mammary epithelial cells, and on milk yield in Saanen goats...
April 26, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29702590/insulin-like-growth-factor-igf-system-in-liver-diseases
#16
REVIEW
Agnieszka Adamek, Aldona Kasprzak
Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2) act in response to growth hormone (GH). Other IGF family components include at least six binding proteins (IGFBP1 to 6), manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R). The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth), and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function...
April 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29693285/higher-variety-and-quantity-of-microrna-139-5p-isoforms-confer-suppressive-role-in-hepatocellular-carcinoma
#17
Hengli Ni, Xiaoxiao Dai, Xueqin Leng, Min Deng, Yan Qin, Qinghua Ji, Chunfang Xu, Jianming Li, Yao Liu
MiRNA isoforms (isomiRs) were defined as an addition or deletion of one or more nucleotides at the 5' or 3' ends or both. Different isomiRs of the same miRNA can target different genes, which have extended the regulatory scale medicated by miRNA. In this study, we systematically analyzed miRNA isoforms in hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas (TCGA) data and further explore their role by in silico and in vitro studies. We found that higher variety and quantity of miR-139-5p isoforms negatively correlated with the malignancy of HCC...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29686696/detection-of-selection-signatures-in-chinese-landrace-and-yorkshire-pigs-based-on-genotyping-by-sequencing-data
#18
Kai Wang, Pingxian Wu, Qiang Yang, Dejuan Chen, Jie Zhou, Anan Jiang, Jideng Ma, Qianzi Tang, Weihang Xiao, Yanzhi Jiang, Li Zhu, Xuewei Li, Guoqing Tang
The domestic pigs have been undergone intense selection pressures for these development of interested traits following domestication and modern breeding. This has altered many traits in most of pig breeds, such as growth rate, body weight, fertility, and immunity. Thus, the objectives of this study were to (1) detect these selection signatures and identify the candidate genes that show evidences of recent artificial selection at the level of whole genome, (2) be beneficial to understand the relationship between genomic structure and phenotypic diversity, and (3) highlight the key roles of these candidate genes in growth and development in the two breeds...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29681666/impact-of-dietary-phosphorous-in-diploid-and-triploid-atlantic-salmon-salmo-salar-l-with-reference-to-early-skeletal-development-in-freshwater
#19
M A Smedley, H Migaud, E L McStay, M Clarkson, P Bozzolla, P Campbell, J F Taylor
In order to assess the effect of dietary phosphorus (P) in reducing vertebral malformations and improving freshwater (FW) performance in triploid Atlantic salmon ( Salmo salar ), both triploid and diploid Atlantic salmon were fed three different dietary P inclusion levels (low: 4.9, medium: 7.7, and high: 9.7 g available P kg-1 ) from first feeding until smolt. Somatic and skeletal response was assessed at fry (~0.5 g), parr (~5 g) and smolt (~45 g) stages. Triploid parr initially grew faster on the high P diet, while groups fed low P resulted in a significantly higher weight at smolt...
March 1, 2018: Aquaculture
https://www.readbyqxmd.com/read/29669935/irs2-mutations-linked-to-invasion-in-pleomorphic-invasive-lobular-carcinoma
#20
Sha Zhu, B Marie Ward, Jun Yu, Asia N Matthew-Onabanjo, Jenny Janusis, Chung-Cheng Hsieh, Keith Tomaszewicz, Lloyd Hutchinson, Lihua Julie Zhu, Dina Kandil, Leslie M Shaw
Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC...
April 19, 2018: JCI Insight
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