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https://www.readbyqxmd.com/read/29451775/fluorescence-imaging-of-huntingtin-mrna-knockdown
#1
Eunseon Oh, Yuhong Liu, Mahesh V Sonar, Diane Merry, Eric Wickstrom
Huntington's disease (HD) is an autosomal-dominant neurodegenerative genetic disorder caused by CAG repeat expansion in exon 1 of the HTT gene. Expression of the mutant gene results in the production of a neurotoxic polyglutamine (polyQ)-expanded huntingtin (Htt) protein. Clinical trials of knockdown therapy of mutant polyglutamine-encoding HTT mRNA in Huntington's disease (HD) have begun. To measure HTT mRNA knockdown effectiveness in human cells, we utilized a fluorescent hybridization imaging agent specific to the region encompassing the human HTT mRNA initiation codon...
February 16, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29440290/a-spatio-temporal-model-of-macrophage-mediated-drug-resistance-in-glioma-immunotherapy
#2
Yongjiang Zheng, Jiguang Bao, Qiyi Zhao, Tianshou Zhou, Xiaoqiang Sun
The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment in driving the development of acquired drug resistance remain elusive, which significantly impedes effective clinical cancer treatment. Recent experimental studies have revealed a macrophage-mediated drug resistance mechanism in which the tumor microenvironment undergoes adaptation in response to macrophage-targeted colony-stimulating factor-1 receptor (CSF1R) inhibition therapy in gliomas...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29438518/obesity-and-high-fat-diet-induce-distinct-changes-in-placental-gene-expression-and-pregnancy-outcome
#3
Erica B Mahany, Xingfa Han, Beatriz C Borges, Sanseray da Silveira Cruz-Machado, Susan J Allen, David Garcia-Galiano, Mark J Hoenerhoff, Nicole H Bellefontaine, Carol F Elias
Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth and neonatal death. In the present study, we aimed to determine the effects of obesity on pregnancy outcome and placental gene expression in preclinical mouse models of genetic and nutritional obesity. The leptin receptor null reactivatable (LepRloxTB), the LepR deficient (Leprdb/+) and high fat diet (HFD) fed mice were assessed for fertility, pregnancy outcome, placental morphology and placental transcriptome using standard qPCR and qPCR arrays...
February 9, 2018: Endocrinology
https://www.readbyqxmd.com/read/29415074/extraocular-muscle-regeneration-in-zebrafish-requires-late-signals-from-insulin-like-growth-factors
#4
Alfonso Saera-Vila, Ke'ale W Louie, Cuilee Sha, Ryan M Kelly, Phillip E Kish, Alon Kahana
Insulin-like growth factors (Igfs) are key regulators of key biological processes such as embryonic development, growth, and tissue repair and regeneration. The role of Igf in myogenesis is well documented and, in zebrafish, promotes fin and heart regeneration. However, the mechanism of action of Igf in muscle repair and regeneration is not well understood. Using adult zebrafish extraocular muscle (EOM) regeneration as an experimental model, we show that Igf1 receptor blockage using either chemical inhibitors (BMS754807 and NVP-AEW541) or translation-blocking morpholino oligonucleotides (MOs) reduced EOM regeneration...
2018: PloS One
https://www.readbyqxmd.com/read/29401624/insulin-and-igf1-receptors-are-essential-for-the-development-and-steroidogenic-function-of-adult-leydig-cells
#5
Yasmine Neirijnck, Pierre Calvel, Karen R Kilcoyne, Françoise Kühne, Isabelle Stévant, Richard J Griffeth, Jean-Luc Pitetti, Silvana A Andric, Meng-Chun Hu, François Pralong, Lee B Smith, Serge Nef
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, and testicular function. Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, insulin receptor (INSR) and type-I insulin-like growth factor receptor (IGF1R), have not, to our knowledge, been investigated. We show here that specific deletion of both Insr and Igf1r in steroidogenic cells in mice leads to severe alterations of adrenocortical and testicular development...
January 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29399196/microarray-pathway-analysis-indicated-that-mitogen-activated-protein-kinase-extracellular-signal-regulated-kinase-and-insulin-growth-factor-1-signaling-pathways-were-inhibited-by-small-interfering-rna-against-at-rich-interactive-domain-1a-in-endometrial-cancer
#6
Ye Yang, Wei Bao, Zhengyu Sang, Yongbing Yang, Meng Lu, Xiaowei Xi
Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29393358/microrna-let-7g-inhibits-angiotensin-ii-induced-endothelial-senescence-via-the-lox-1-independent-mechanism
#7
Po-Yuan Hsu, Wen-Yi Lin, Ruey-Tay Lin, Suh-Hang H Juo
Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs). Overactivation of IGF signaling has been implicated in promoting the aging process. Lectin‑like oxidized low‑density lipoprotein (oxLDL) receptor‑1 (LOX‑1) is a scavenger receptor that mediates the internalization of oxLDL into cells...
January 23, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29392223/a-new-role-of-growth-hormone-and-insulin-growth-factor-receptor-type-1-in-neonatal-inflammatory-nociception
#8
Alfredo Manzano-García, Mohammed Gamal-Eltrabily
Growth hormone (GH) and insulin growth factor 1 (IGF1) are implicated in nociceptive processing; it has been reported that the latter participates in neonatal inflammatory nociception. In the target article, the authors propose that local inflammation evoked by carrageenan administration in mice produces a decrease in the local GH levels and an increment of IGF1 receptors type 1 expression, this produces behavioral nociception and peripheral sensitization that can be prevented by GH systemic administration pretreatment...
July 2017: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/29330302/controlled-dimerization-of-insulin-like-growth-factor-1-and-insulin-receptors-reveal-shared-and-distinct-activities-of-holo-and-hybrid-receptors
#9
Jingci Chen, Alison M Nagle, Yu-Fen Wang, David N Boone, Adrian V Lee
Breast cancer development and progression is influenced by insulin-like growth factor 1 (IGF1R) and insulin receptor (InsR) signaling that drive cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and InsR form IGF1R/InsR hybrid receptors (HybR) consisting of one molecule of IGF1R and one molecule of InsR. The specific signaling and functions of HybR are largely unknown as HybR is activated by both IGF1 and insulin, and no cellular system expresses HybR in the absence of holo-IGF1R or holo-InsR...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29314608/unc-120-srf-independently-controls-muscle-aging-and-lifespan-in-caenorhabditis-elegans
#10
Adeline Mergoud Dit Lamarche, Laurent Molin, Laura Pierson, Marie-Christine Mariol, Jean-Louis Bessereau, Kathrin Gieseler, Florence Solari
Aging is commonly defined as the loss of global homeostasis, which results from progressive alteration of all organs function. This model is currently challenged by recent data showing that interventions that extend lifespan do not always increase the overall fitness of the organism. These data suggest the existence of tissue-specific factors that regulate the pace of aging in a cell-autonomous manner. Here, we investigated aging of Caenorhabditis elegans striated muscles at the subcellular and the physiological level...
January 3, 2018: Aging Cell
https://www.readbyqxmd.com/read/29300910/foxo1-is-required-for-most-of-the-metabolic-and-hormonal-perturbations-produced-by-hepatic-insulin-receptor-deletion-in-male-mice
#11
Alisha V Ling, Mary E Gearing, Ivana Semova, Dong-Ju Shin, Rebecca Clements, Zon W Lai, Sudha B Biddinger
Insulin coordinates the complex response to feeding, affecting numerous metabolic and hormonal pathways. FoxO1 is one of several signaling molecules downstream of insulin; FoxO1 drives gluconeogenesis and is suppressed by insulin. To determine the role of FoxO1 in mediating other actions of insulin, we studied mice with hepatic deletion of the insulin receptor, FoxO1, or both. We found that mice with deletion of the insulin receptor alone showed not only hyperglycemia, but a 40% decrease in hepatic Igf1 and delayed growth during the first two months of life, a 24-fold increase in soluble leptin receptor and a 19-fold increase in plasma leptin levels...
December 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/29288977/maternal-nutritional-restriction-during-late-gestation-impairs-development-of-the-reproductive-organs-in-both-male-and-female-lambs
#12
F Hoffman, E Boretto, S Vitale, V Gonzalez, G Vidal, M F Pardo, M F Flores, F Garcia, G Bagnis, O C M Queiroz, M B Rabaglino
Maternal nutritional restrictions during late gestation could lead to fetal hypoglycemia. Glucose levels in the fetal sheep regulate circulating insulin-like growth factor 1 (IGF1) levels, which stimulate cell proliferation and differentiation of reproductive organs after binding to its own receptor or estrogen receptors. The objective of this study was to determine the effects of subnutrition of ewes during the last trimester of gestation on the serum glucose/IGF1 levels and development of reproductive organs in their lambs...
December 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/29251331/upregulation-of-igf1-by-tumor-associated-macrophages-promotes-the-proliferation-and-migration-of-epithelial-ovarian-cancer-cells
#13
Li Liu, Xinjing Wang, Xiaoduan Li, Xiaoli Wu, Meiling Tang, Xipeng Wang
Ovarian cancer (OC), of which epithelial ovarian cancer (EOC) is the most common, is the deadliest gynecological tumor because of the difficulties in detection at early stages, and metastasis and chemoresistance at advanced stages. Tumor-associated macrophages (TAMs) differentiate through alternative pathways and play important roles in tumor growth and metastasis. However, the underlying mechanism remains unclear. Here, we established a mouse TAM model using bone marrow monocytes and conditioned medium (CM) of TAMs to culture ID8 mouse EOC cells...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29249625/genetic-disorders-of-gh-action-pathway
#14
Horacio M Domené, Gustavo Fierro-Carrión
While insensitivity to GH (GHI) is characterized by low IGF-I levels, normal or elevated GH levels, and lack of IGF-I response to GH treatment, IGF-I resistance is characterized by elevated IGF-I levels with normal/high GH levels. Several genetic defects are responsible for impairment of GH and IGF-I actions resulting in short stature that could affect intrauterine growth or be present in the postnatal period. The genetic defects affecting GH and/or IGF-I action can be divided into five different groups: GH insensitivity by defects affecting the GH receptor (GHR), the intracellular GH signaling pathway (STAT5B, STAT3, IKBKB, IL2RG, PIK3R1), the synthesis of insulin-like growth factors (IGF1, IGF2), the transport/bioavailability of IGFs (IGFALS, PAPPA2), and defects affecting IGF-I sensitivity (IGF1R)...
December 12, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29248211/influence-of-ad-libitum-milk-replacer-feeding-and-butyrate-supplementation-on-the-systemic-and-hepatic-insulin-like-growth-factor-i-and-its-binding-proteins-in-holstein-calves
#15
D Frieten, C Gerbert, C Koch, G Dusel, K Eder, A Hoeflich, B Mielenz, H M Hammon
Ad libitum milk feeding and butyrate (B) supplementation have the potential to stimulate postnatal growth and development in calves. The somatotropic axis is the main endocrine regulator of postnatal growth and may be affected by both ad libitum milk replacer (MR) feeding and B supplementation in calves. We hypothesized that ad libitum MR feeding and B supplementation stimulate systemic and hepatic insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP) in preweaning calves. Sixty-four (32 male, 32 female) Holstein calves were examined from birth until wk 11 of life...
December 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29238946/papp-a2-a-new-key-regulator-of-growth
#16
Magdalena Banaszak-Ziemska, Marek Niedziela
Short stature is the main problem that paediatric endocrinologists have to grapple with. Endocrine disorders account for only 5% of patients with short stature, but this is still one of the most common causes of reports to the endocrine clinic and hospitalisation in the endocrine department. A properly functioning growth hormone/insulin-like growth factor (GH/IGF) axis is one of the most important factors in proper growth. A lot of genetic defects in this axis lead to syndromes marked by impaired growth, like Laron syndrome, muta-tions in the STAT5B, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 1 receptor (IGF1R) and mutations in the acid labile subunit (ALS)...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/29217479/distinct-lipidomic-profiles-in-models-of-physiological-and-pathological-cardiac-remodeling-and-potential-therapeutic-strategies
#17
Yow Keat Tham, Kevin Huynh, Natalie A Mellett, Darren C Henstridge, Helen Kiriazis, Jenny Y Y Ooi, Aya Matsumoto, Natalie L Patterson, Junichi Sadoshima, Peter J Meikle, Julie R McMullen
Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially-regulated lipids could modulate heart size and function...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29212519/gper-mediates-the-angiocrine-actions-induced-by-igf1-through-the-hif-1%C3%AE-vegf-pathway-in-the-breast-tumor-microenvironment
#18
Ernestina M De Francesco, Andrew H Sims, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti, Robert B Clarke
BACKGROUND: The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells...
December 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29204986/polymorphisms-of-the-igf1-gene-and-their-association-with-growth-traits-serum-concentration-and-expression-rate-of-igf1-and-igf1r-in-buffalo
#19
Mohammed A El-Magd, Ayman A Saleh, Abeer A Nafeaa, Shymaa M El-Komy, Mohamed A Afifi
The insulin-like growth factor 1 (IGF1) gene is a member of the group of somatotropin axis genes that play a significant role in cell proliferation and growth of muscles. Here, we searched for polymorphisms in buffalo IGF1 and found two novel single nucleotide polymorphisms (SNPs), G64A and G280A, in the noncoding sequences of exon 1 and exon 4, respectively. Statistical analysis of different genotypes showed that the individuals with GG genotypes had significantly (P<0.05) higher body weight (BW) and average daily gain (ADG) than those with other genotypes at ages of 3-6 months in G64A SNP and 6-9 months in G280A SNP...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29195026/effects-of-the-insulin-like-growth-factor-system-on-testicular-differentiation-and-function-a-review-of-the-literature
#20
REVIEW
R Cannarella, R A Condorelli, S La Vignera, A E Calogero
We recently described the occurrence of cryptorchidism, oligoasthenoteratozoospermia, and genital abnormalities in patients with distal 15q chromosome structural abnormalities. This observation brought us to hypothesize that insulin-like growth factor (IGF) receptor (IGF1R), mapping on the 15q 26.3 chromosomal band, may be involved in testicular function. To further evaluate this topic, we reviewed in vitro and in vivo studies exploring the role of the IGF system [IGF1, IGF2, IGF1R, insulin receptor substrates (IRS)] at the testicular level both in animals and in humans...
December 1, 2017: Andrology
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