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https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#1
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of IRES trans-acting factor La protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#2
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28089693/effects-of-six-priority-controlled-phthalate-esters-with-long-term-low-dose-integrated-exposure-on-male-reproductive-toxicity-in-rats
#3
Hai-Tao Gao, Run Xu, Wei-Xin Cao, Liang-Liang Qian, Min Wang, Lingeng Lu, Qian Xu, Shu-Qin Yu
Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on male rat reproductive system and further to explore the underlying mechanisms of the reproductive toxicity...
January 12, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28088735/long-non-coding-rna-ccat1-promotes-human-retinoblastoma-so-rb50-and-y79-cells-through-negative-regulation-of-mir-218-5p
#4
Hongxu Zhang, Jianguang Zhong, Zhenyu Bian, Xiang Fang, You Peng, Yongping Hu
OBJECTIVE: To investigate the regulatory role and potential mechanism of long non-coding RNAs (lncRNA) in human retinoblastoma (RB). METHODS: The lncRNA profile in RB tissues were analyzed by microarray and quantitative reverse transcription PCR (qRT-PCR). One of the identified lncRNAs (LncRNA CCAT1) was selected for further experiments. SO-RB50 and Y79 cells were transfected with negative control, siRNA targeting lncRNA CCAT1 (si-CCAT1) and si-CCAT1+miR218-5p inhibitor, respectively...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28087664/human-blood-cd1c-dendritic-cells-encompass-cd5high-and-cd5low-subsets-that-differ-significantly-in-phenotype-gene-expression-and-functions
#5
Xiangyun Yin, Haisheng Yu, Xiaoyang Jin, Jingyun Li, Hao Guo, Quanxing Shi, Zhao Yin, Yong Xu, Xuefei Wang, Rong Liu, Shouli Wang, Liguo Zhang
There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4(+) naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c(+) cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077718/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#6
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage-specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin-linked kinase (ILK) is an important protein that is expressed at the inner margins of the plasma membrane and can mediate some of these signals...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28068431/cil-102-induced-cell-cycle-arrest-and-apoptosis-in-colorectal-cancer-cells-via-upregulation-of-p21-and-gadd45
#7
Wen-Shih Huang, Yi-Hung Kuo, Hsing-Chun Kuo, Meng-Chiao Hsieh, Cheng-Yi Huang, Ko-Chao Lee, Kam-Fai Lee, Chien-Heng Shen, Shui-Yi Tung, Chih-Chuan Teng
CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is a well-known, major active agent of the alkaloid derivative of Camptotheca acuminata with valuable biological properties, including anti-tumorigenic activity. In this study, we investigated the molecular mechanisms by which CIL-102 mediated the induction of cell death, and we performed cell cycle G2/M arrest to clarify molecular changes in colorectal cancer cells (CRC). Treatment of DLD-1 cells with CIL-102 resulted in triggering the extrinsic apoptosis pathway through the activation of Fas-L, caspase-8 and the induction of Bid cleavage and cytochrome c release in a time-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28055975/mitotic-catastrophe-and-cell-cycle-arrest-are-alternative-cell-death-pathways-executed-by-bortezomib-in-rituximab-resistant-b-cell-lymphoma-cells
#8
Juan J Gu, Gregory P Kaufman, Cory Mavis, Myron S Czuczman, Francisco J Hernandez-Ilizaliturri
The ubiqutin-proteasome system (UPS) plays a role in rituximab-chemotherapy resistance and bortezomib (BTZ) possesses caspase-dependent (i.e. Bak stabilization) and a less characterized caspase-independent mechanism-of-action(s). Here, we define BTZ-induced caspase-independent cell death pathways. A panel of rituximab-sensitive (RSCL), rituximab-resistant cell lines (RRCL) and primary tumor cells derived from lymphoma patients (N = 13) were exposed to BTZ. Changes in cell viability, cell-cycle, senescence, and mitotic index were quantified...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049917/synthesis-docking-study-and-kinase-inhibitory-activity-of-a-number-of-new-substituted-pyrazolo-3-4-c-pyridines
#9
Meropi Sklepari, Nikolaos Lougiakis, Athanasios Papastathopoulos, Nicole Pouli, Panagiotis Marakos, Vassilios Myrianthopoulos, Thomas Robert, Stéphane Bach, Emmanuel Mikros, Sandrine Ruchaud
A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28049589/a-triple-exon-skipping-luciferase-reporter-assay-identifies-a-new-clk-inhibitor-pharmacophore
#10
Yihui Shi, Jaehyeon Park, Chandraiah Lagisetti, Wei Zhou, Lidia C Sambucetti, Thomas R Webb
The splicing of pre-mRNA is a critical process in normal cells and is deregulated in cancer. Compounds that modulate this process have recently been shown to target a specific vulnerability in tumors. We have developed a novel cell-based assay that specifically activates luciferase in cells exposed to SF3B1 targeted compounds, such as sudemycin D6. This assay was used to screen a combined collection of approved drugs and bioactive compounds. This screening approach identified several active hits, the most potent of which were CGP-74514A and aminopurvalanol A, both have been reported to be cyclin-dependent kinases (CDKs) inhibitors...
December 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28012958/romidepsin-induces-g2-m-phase-arrest-via-erk-cdc25c-cdc2-cyclinb-pathway-and-apoptosis-induction-through-jnk-c-jun-caspase3-pathway-in-hepatocellular-carcinoma-cells
#11
Wei-Jian Sun, He Huang, Bin He, Dan-Hong Hu, Pi-Hong Li, Yao-Jun Yu, Xiao-Hu Zhou, Zhen Lv, Lei Zhou, Tian-Ye Hu, Zhi-Chao Yao, Ming-Dong Lu, Xian Shen, Zhi-Qiang Zheng
The aim of the study is to demonstrate the effect of Romidepsin in hepatocellular carcinoma (HCC) by inducing G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis through JNK/c-Jun/caspase3 pathway in vitro and in vivo. Human HCC cell lines were cultured with Romidepsin and DMSO (negative control) and 5-fluorouracil (positive control). Then the cells' viability and apoptosis were determined by cell proliferation assay and flow cytometry. Protein concentrations and expression changes were measured by Western blot...
December 22, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28009925/synthesis-in-vitro-and-in-vivo-evaluation-of-new-hybrids-of-millepachine-and-phenstatin-as-potent-tubulin-polymerization-inhibitors
#12
Baijiao An, Shun Zhang, Jun Yan, Ling Huang, Xingshu Li
In this paper, a series of millepachine derivatives were synthesized and evaluated as tubulin polymerization inhibitors. The optimal compound 5i, (3-hydroxy-4-methoxyphenyl)(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)methanone, displayed the highest cytotoxicity toward a series of cancer cells (ranging from 18 to 45 nM of IC50). Further investigation revealed that 5i significantly repressed the multidrug resistant cells (A549/CDDP, A2780/TAX) and had little cytotoxicity towards human normal cells (HLF, BJ). Cellular mechanism studies demonstrated that 5i induced G2/M phase arrest and apoptosis, which was associated with the collapse of the mitochondrial membrane potential (MMP)...
December 23, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28000414/identification-of-clk1%C3%A2-inhibitors-by-a-fragment-linking-based-virtual-screening
#13
Anne Walter, Apirat Chaikuad, Nadège Loaëc, Lutz Preu, Stefan Knapp, Laurent Meijer, Conrad Kunick, Oliver Koch
Alternative splicing plays an important role in the regulation of protein biosynthesis. CDC2-like kinases (CLKs) phosphorylate splicing factors rendering them a potential target for treating diseases caused by splicing dysregulation. As selective and potent inhibitors of CLK1 are still lacking, a fragment-linking based virtual screening campaign was successfully applied to identify new inhibitors showing activity on CLK1. These inhibitors exhibit a novel 2,4-substituted 1,3-thiazole scaffold that is suitable for further modification...
December 21, 2016: Molecular Informatics
https://www.readbyqxmd.com/read/27998766/evaluation-of-deoxynivalenol-induced-toxic-effects-on-mouse-endometrial-stromal-cells-cell-apoptosis-and-cell-cycle
#14
Yujian Dai, Haiqiang Xie, Yinxue Xu
Deoxynivalenol (DON) is a type B trichothecene mycotoxin which has toxic effects on humans and animals. Although DON has been studied in various cell types for its cytotoxicity, there is litter information about the effects of DON on mouse endometrial stromal cells (ESCs). Thus, in this study, we investigated the toxic effects of DON on mouse ESCs and its possible mechanisms. DON inhibited the cell viability in a dose- and time-dependent manner. TUNEL assay results showed that DON caused apoptosis and TUNEL-positive cells increased with increasing DON concentrations in mouse ESCs...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27988300/zinc-finger-factor-znf121-is-a-myc-interacting-protein-functionally-affecting-myc-and-cell-proliferation-in-epithelial-cells
#15
Ang Luo, Xuan Zhang, Liya Fu, Zhengmao Zhu, Jin-Tang Dong
MYC is a potent oncoprotein that modulates multiple cellular processes including proliferation, apoptosis, differentiation, stemness, senescence, and migration. Functioning primarily as a transcriptional factor, MYC interacts with a large number of proteins, and identification and characterization of MYC-interacting proteins are important for understanding how MYC functions. In this study, we used different systems to demonstrate that a novel zinc finger transcription factor, ZNF121, physically interacted with MYC, and the interaction involved their N-terminal regions...
December 20, 2016: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/27986611/antrodia-salmonea-induces-g2-cell-cycle-arrest-in-human-triple-negative-breast-cancer-mda-mb-231-cells-and-suppresses-tumor-growth-in-athymic-nude-mice
#16
Chia-Ting Chang, You-Cheng Hseu, Varadharajan Thiyagarajan, Hui-Chi Huang, Li-Sung Hsu, Pei-Jane Huang, Jer-Yuh Liu, Jiunn-Wang Liao, Hsin-Ling Yang
ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. MATERIALS AND METHODS: In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. RESULTS: AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27981550/knockdown-of-tripartite-motif-59-trim59-inhibits-tumor-growth-in-prostate-cancer
#17
W-Y Lin, H Wang, X Song, S-X Zhang, P-S Zhou, J-M Sun, J-S Li
OBJECTIVE: Members of the tripartite motif (TRIM) protein family contain a highly conserved N-terminal really interesting new gene (RING) domain that is involved in regulating transcriptional factors and tumor suppressors. In this study, the effects of TRIM59 expression on tumor growth were investigated in prostate cancer. MATERIALS AND METHODS: The expression of TRIM59 in prostate cancer tissues (n = 15) and prostate cancer cell lines was determined by quantitative reverse transcriptase-PCR (qRT-PCR), Western blotting, and immunohistochemistry...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27965041/trichodermin-induces-c-jun-n-terminal-kinase-dependent-apoptosis-caused-by-mitotic-arrest-and-dna-damage-in-human-p53-mutated-pancreatic-cancer-cells-and-xenografts
#18
Ming-Hsien Chien, Tzong-Huei Lee, Wei-Jiunn Lee, Yen-Hsiu Yeh, Tsai-Kun Li, Po-Chuan Wang, Jih-Jung Chen, Jyh-Ming Chow, Yung-Wei Lin, Michael Hsiao, Shih-Wei Wang, Kuo-Tai Hua
Pancreatic cancer is an aggressive malignancy, which generally responds poorly to chemotherapy. In this study, trichodermin, an endophytic fungal metabolite from Nalanthamala psidii, was identified as a potent and selective antitumor agent in human pancreatic cancer. Trichodermin exhibited antiproliferative effects against pancreatic cancer cells, especially p53-mutated cells (MIA PaCa-2 and BxPC-3) rather than normal pancreatic epithelial cells. We found that trichodermin induced caspase-dependent and mitochondrial intrinsic apoptosis...
December 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27956520/dual-inhibition-of-key-proliferation-signaling-pathways-in-triple-negative-breast-cancer-cells-by-a-novel-derivative-of-taiwanin-a
#19
Yueh-Hsiung Kuo, En-Pei Isabel Chiang, Che-Yi Chao, Raymond L Rodriguez, Pei-Yu Chou, Shu-Yao Tsai, Man-Hui Pai, Feng-Yao Tang
The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI-3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, we report that 3,4-bis-3,4,5- trimethoxybenzylidene-dihydrofuran (BTMB), a novel derivative of Taiwanin A, significantly inhibited the proliferation of triple negative breast cancer (TNBC) cells both in vitro and in vivo...
December 12, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27942359/cytolethal-distending-toxin-from-campylobacter-jejuni-requires-the-cytoskeleton-for-toxic-activity
#20
Estela T Méndez-Olvera, Jaime A Bustos-Martínez, Yolanda López-Vidal, Antonio Verdugo-Rodríguez, Daniel Martínez-Gómez
BACKGROUND: Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. OBJECTIVES: The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus...
October 2016: Jundishapur Journal of Microbiology
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