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https://www.readbyqxmd.com/read/29458137/bisphenol-a-alters-oocyte-maturation-by-prematurely-closing-gap-junctions-in-the-cumulus-cell-oocyte-complex
#1
Deyanira Guadalupe Acuña-Hernández, Laura Arreola-Mendoza, Ramsés Santacruz-Márquez, Sihomara Patricia García-Zepeda, Lyda Yuliana Parra-Forero, Jesús Alberto Olivares-Reyes, Isabel Hernández-Ochoa
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC...
February 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29457931/synthesis-and-characterization-of-nanodiamond-growth-factor-complexes-towards-applications-in-oral-implantation-and-regenerative-medicine
#2
Julie Bang, Caleb Ting, Peter Wang, Ted Kim, Kenneth Wang, Theodore Kee, Darron Miya, Dean Ho, Dong-Keun Lee
Current challenges in the field of regenerative medicine include the need to deliver sustained concentrations of growth factors and genes that are required to induce the repair of deficient tissues. Enhancement of drug delivery and uptake may result in improved growth factor efficacy. Nanodiamonds (NDs) were explored as potential growth factor delivery agents due to the many favorable properties that they possess. For example, ND's biocompatibility has been extensively validated pre-clinically. In addition, they can be scalably produced through impact events such as detonation...
February 19, 2018: Journal of Oral Implantology
https://www.readbyqxmd.com/read/29455659/receptor-tyrosine-kinases-and-downstream-pathways-as-druggable-targets-for-cancer-treatment-the-current-arsenal-of-inhibitors
#3
REVIEW
Wagner Ricardo Montor, Andrei Ronaldo Oliveira Silva Escartin Salas, Fabiana Henriques Machado de Melo
Searching for targets that allow pharmacological inhibition of cell proliferation in over-proliferative states, such as cancer, leads us to finely understand the complex mechanisms orchestrating the perfect control of mitosis number, frequency and pace as well as the molecular arrangements that induce cells to enter functional quiescence and brings them back to cycling in specific conditions. Although the mechanisms regulating cell proliferation have been described several years ago, never before has so much light been shed over this machinery as during the last decade when therapy targets have been explored and molecules, either synthetic or in the form of antibodies with the potential of becoming cancer drugs were produced and adjusted for specific binding and function...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455656/the-e3-ubiquitin-ligase-nedd4-mediates-cell-migration-signaling-of-egfr-in-lung-cancer-cells
#4
Genbao Shao, Ranran Wang, Aiqin Sun, Jing Wei, Ke Peng, Qian Dai, Wannian Yang, Qiong Lin
BACKGROUND: EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. METHODS: Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29453167/electrochemical-detection-of-methylated-dna-on-a-microfluidic-chip-with-nanoelectrokinetic-pre-concentration
#5
Sung A Hong, Yong-June Kim, Sung Jae Kim, Sung Yang
DNA methylation is considered to be a promising marker for the early diagnosis and prognosis of cancer. However, direct detection of the methylated DNAs in clinically relevant samples is still challenging because of its extremely low concentration (~fM). Here, an integrated microfluidic chip is reported, which is capable of pre-concentrating the methylated DNAs using ion concentration polarization (ICP) and electrochemically detecting the pre-concentrated DNAs on a single chip. The proposed chip is the first demonstration of an electrochemical detection of both level and concentration of the methylated DNAs by integrating a DNA pre-concentration unit without gene amplification...
February 1, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29452913/photo-immobilized-egf-chemical-gradients-differentially-impact-breast-cancer-cell-invasion-and-drug-response-in-defined-3d-hydrogels
#6
Stephanie A Fisher, Roger Y Tam, Ana Fokina, M Mohsen Mahmoodi, Mark D Distefano, Molly S Shoichet
Breast cancer cell invasion is influenced by growth factor concentration gradients in the tumor microenvironment. However, studying the influence of growth factor gradients on breast cancer cell invasion is challenging due to both the complexities of in vivo models and the difficulties in recapitulating the tumor microenvironment with defined gradients using in vitro models. A defined hyaluronic acid (HA)-based hydrogel crosslinked with matrix metalloproteinase (MMP) cleavable peptides and modified with multiphoton labile nitrodibenzofuran (NDBF) was synthesized to photochemically immobilize epidermal growth factor (EGF) gradients...
February 13, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#7
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#8
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447132/role-of-gpcr-mu-opioid-receptor-tyrosine-kinase-epidermal-growth-factor-crosstalk-in-opioid-induced-hyperalgesic-priming-type-ii
#9
Dionéia Araldi, Luiz F Ferrari, Jon D Levine
Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors...
January 11, 2018: Pain
https://www.readbyqxmd.com/read/29445239/the-urokinase-receptor-induces-a-mesenchymal-gene-expression-signature-in-glioblastoma-cells-and-promotes-tumor-cell-survival-in-neurospheres
#10
Andrew S Gilder, Letizia Natali, Danielle M Van Dyk, Cristina Zalfa, Michael A Banki, Donald P Pizzo, Huawei Wang, Richard L Klemke, Elisabetta Mantuano, Steven L Gonias
PLAUR encodes the urokinase receptor (uPAR), which promotes cell survival, migration, and resistance to targeted cancer therapeutics in glioblastoma cells in culture and in mouse model systems. Herein, we show that patient survival correlates inversely with PLAUR mRNA expression in gliomas of all grades, in glioblastomas, and in the subset of glioblastomas that demonstrate the mesenchymal gene expression signature. PLAUR clusters with genes that define the more aggressive mesenchymal subtype in transcriptome profiles of glioblastoma tissue and glioblastoma cells in neurospheres, which are enriched for multipotent cells with stem cell-like qualities...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444453/efferocytosis-in-atherosclerotic-lesions-malfunctioning-regulatory-pathways-and-control-mechanisms
#11
REVIEW
Amir Tajbakhsh, Mehdi Rezaee, Petri T Kovanen, Amirhossein Sahebkar
Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process...
February 11, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29438748/neuregulin-1-discovered-as-a-cleavage-target-for-the-hcv-ns3-4a-protease-by-a-microfluidic-membrane-protein-array
#12
Nika Schwartz, Michal Pellach, Yair Glick, Reuven Gil, Gahl Levy, Dorit Avrahami, Efrat Barbiro-Michaely, Yaakov Nahmias, Doron Gerber
The hepatitis C virus (HCV) non-structural protein 3 (NS3) is essential for HCV maturation. The NS3/4A protease is a target for several HCV treatments and is a well-known target for HCV drug discovery. The protein is membrane associated and thus probably interacts with other membrane proteins. However, the vast majority of known NS3 host partners are soluble proteins rather than membrane proteins, most likely due to lack of appropriate platforms for their discovery. Utilization of an integrated microfluidics platform enables analysis of membrane proteins in their native form...
February 10, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29438745/an-automated-epifluorescence-microscopy-imaging-assay-for-the-identification-of-phospho-akt-level-modulators-in-breast-cancer-cells
#13
Elke Kaemmerer, Dane Turner, Amelia A Peters, Sarah J Roberts-Thomson, Gregory R Monteith
AKT is an enzyme of the PI3K/pAKT pathway, regulating proliferation and cell survival. High basal levels of active, phosphorylated AKT (pAKT) are associated with tumor progression and therapeutic resistance in some breast cancer subtypes, including HER2 positive breast cancers. Various stimuli can increase pAKT levels and elevated basal pAKT levels are a feature of PTEN-deficient breast cancer cell lines. The aim of this study was to develop an assay able to identify modulators of pAKT levels using an automated epifluorescence microscope and high content analysis...
February 10, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29438695/eradication-of-triple-negative-breast-cancer-cells-by-targeting-glycosylated-pd-l1
#14
Chia-Wei Li, Seung-Oe Lim, Ezra M Chung, Yong-Soo Kim, Andrew H Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P Perillo, Andrew K Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A Sahin, Gabriel N Hortobagyi, Stephen S Yoo, Mien-Chie Hung
Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438534/both-in-vivo-fsh-depletion-and-follicular-exposure-to-gonadotrophin-releasing-hormone-analogues-in-vitro-are-not-effective-to-prevent-follicular-depletion-during-chemotherapy-in-mice
#15
F Horicks, G Van Den Steen, C Gervy, H J Clarke, I Demeestere
STUDY QUESTION: Does fertility preservation using gonadotrophin-releasing hormone (GnRH) analogues during chemotherapy act through a direct effect on the ovary or through inhibition of FSH secretion? SUMMARY ANSWER: The absence of FSH in vivo and the direct exposition of ovarian follicles to GnRH analogues in vitro did not prevent chemotherapy-induced ovarian damage. WHAT IS KNOWN ALREADY: The potential mechanisms of action of GnRH analogues in protecting ovaries against chemotherapy damage remain poorly understood...
February 9, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29436549/enhanced-delivery-of-sirna-to-triple-negative-breast-cancer-cells-in-vitro-and-in-vivo-through-functionalizing-lipid-coated-calcium-phosphate-nanoparticles-with-dual-target-ligands
#16
Jie Tang, Christopher B Howard, Stephen M Mahler, Kristofer J Thurecht, Leaf Huang, Zhi Ping Xu
The conjugation of ligands to nanoparticle platforms for the target delivery of therapeutic agents to the tumor tissue is one of the promising anti-cancer strategies. However, conventional nanoparticle platforms are not so effective in terms of the selectivity and transfection efficiency. In this study, we designed and developed a dual-target drug/gene delivery system based on lipid-coated calcium phosphate (LCP) nanoparticles (NPs) for significantly enhanced siRNA cellular uptake and transfection efficiency...
February 13, 2018: Nanoscale
https://www.readbyqxmd.com/read/29434677/the-constitutively-active-pkg-ii-mutant-effectively-inhibits-gastric-cancer-development-via-a-blockade-of-egf-egfr-associated-signalling-cascades
#17
Yan Wu, Miaomiao Yuan, Wenbin Su, Miaolin Zhu, Xiaoyuan Yao, Ying Wang, Hai Qian, Lu Jiang, Yan Tao, Min Wu, Ji Pang, Yongchang Chen
Type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) is a membrane-anchored enzyme expressed mainly in the intestinal mucosa and the brain, and is associated with various physiological or pathological processes. Upregulation of PKG II is known to induce apoptosis and inhibit proliferation and metastasis of cancer cells. The inhibitory effect of PKG II has been shown to be dependent on the inhibition of the activation of epidermal growth factor receptor (EGFR) and blockade of EGFR downstream signal transduction in vitro...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29429958/human-ipsc-derived-posterior-gut-progenitors-are-expandable-and-capable-of-forming-gut-and-liver-organoids
#18
Ran-Ran Zhang, Masaru Koido, Tomomi Tadokoro, Rie Ouchi, Tatsuya Matsuno, Yasuharu Ueno, Keisuke Sekine, Takanori Takebe, Hideki Taniguchi
Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2 + posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm...
February 1, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29428518/efemp2-mediates-galnt14-dependent-breast-cancer-cell-invasion
#19
Tao Zuo, Jinshuai Shan, Yang Liu, Rong Xie, Xiaochun Yu, Chen Wu
N-Acetylgalactosaminyltransferase-14 (GALNT14) is a member of acetylgalactosaminyltransferases family. We have shown that GALNT14 could promote breast cancer cell invasion. However, the underlying molecular mechanism is unclear. Here, using yeast two hybrid, we find that EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) interacts with GALNT14. Both in vitro and in vivo binding assays show that EFEMP2 is associated with GALNT14. Moreover, we find that GALNT14 mediates glycosylation of EFEMP2...
February 7, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29427772/circulating-angiopoietin-2-and-its-soluble-receptor-tie-2-concentrations-are-related-to-inflammatory-markers-in-the-general-population
#20
Elisabeth A Schuldt, Wolfgang Lieb, Marcus Dörr, Markus M Lerch, Henry Völzke, Matthias Nauck, Nele Friedrich
BACKGROUND: The Angiopoietin/Tie (Tyrosine kinase with Ig and EGF homology domains) signaling axis has crucial influences on angiogenesis and the vasculature's reorganization. Moreover, angiopoietin-2 (Ang2) is discussed as a biomarker for diseases' severity and development. Previous studies reported increased Ang2 levels in patients with inflammatory diseases and associations of Ang2 with inflammation markers in relatively small samples. We aimed to assess the relation of Ang2 and Tie2 with inflammation markers in the general population...
February 7, 2018: Cytokine
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