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https://www.readbyqxmd.com/read/28642576/upregulation-of-mir-223-in-the-rat-liver-inhibits-proliferation-of-hepatocytes-under-simulated-microgravity
#1
Yongjie Chen, Ji Xu, Chao Yang, Hongyu Zhang, Feng Wu, Jian Chen, Kai Li, Hailong Wang, Yu Li, Yinghui Li, Zhongquan Dai
Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports...
June 23, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28638452/targeting-tpx2-suppresses-the-tumorigenesis-of-hepatocellular-carcinoma-cells-resulting-in-arrested-mitotic-phase-progression-and-increased-genomic-instability
#2
Chao-Wen Hsu, Yu-Chia Chen, Hsing-Hao Su, Guan-Jin Huang, Chih-Wen Shu, Tony Tong-Lin Wu, Hung-Wei Pan
Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28618413/induction-of-apoptosis-in-heparg-cell-line-by-aloe-emodin-through-generation-of-reactive-oxygen-species-and-the-mitochondrial-pathway
#3
Xiaoxv Dong, Jing Fu, Xingbin Yin, Changhai Qu, Chunjing Yang, Huyiligeqi He, Jian Ni
BACKGROUND/AIMS: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. METHODS: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28612710/yc-1-induces-g0-g1-phase-arrest-and-mitochondria-dependent-apoptosis-in-cisplatin-resistant-human-oral-cancer-car-cells
#4
Miau-Rong Lee, Chingju Lin, Chi-Cheng Lu, Sheng-Chu Kuo, Je-Wei Tsao, Yu-Ning Juan, Hong-Yi Chiu, Fang-Yu Lee, Jai-Sing Yang, Fuu-Jen Tsai
Oral cancer is a serious and fatal disease. Cisplatin is the first line of chemotherapeutic agent for oral cancer therapy. However, the development of drug resistance and severe side effects cause tremendous problems clinically. In this study, we investigated the pharmacologic mechanisms of YC-1 on cisplatin-resistant human oral cancer cell line, CAR. Our results indicated that YC-1 induced a concentration-dependent and time-dependent decrease in viability of CAR cells analyzed by MTT assay. Real-time image analysis of CAR cells by IncuCyte™ Kinetic Live Cell Imaging System demonstrated that YC-1 inhibited cell proliferation and reduced cell confluence in a time-dependent manner...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28606920/single-cell-dynamics-determines-response-to-cdk4-6-inhibition-in-triple-negative-breast-cancer
#5
Uzma Asghar, Alexis R Barr, Ros Cutts, Matthew Beaney, Irina S Babina, Deepak Sampath, Jennifer Giltnane, Jennifer A Lacap, Lisa Crocker, Amy Young, Alex Pearson, Maria Teresa Herrera-Abreu, Chris Bakal, Nicholas C Turner
Purpose: Triple negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prognosis. We evaluated the activity of CDK4/6 inhibitors across the TNBC subtypes, and investigated mechanisms of sensitivity. <p>Experimental design: A panel of cell lines representative of TNBC were tested for in vitro and in vivo sensitivity to CDK4/6 inhibition. A fluorescent CDK2 activity reporter was used for single cell analysis in conjunction with time-lapse imaging.</p> <p>Results: The luminal androgen receptor (LAR) subtype of TNBC was highly sensitive to CDK4/6 inhibition both in vitro [p<0...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28596299/postexercise-essential-amino-acid-supplementation-amplifies-skeletal-muscle-satellite-cell-proliferation-in-older-men-24%C3%A2-hours-postexercise
#6
Paul T Reidy, Christopher S Fry, Jared M Dickinson, Micah J Drummond, Blake B Rasmussen
Aged skeletal muscle has an attenuated and delayed ability to proliferate satellite cells in response to resistance exercise. The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is a focal point for cell growth, however, the effect of postexercise mTORC1 activation on human skeletal muscle satellite cell (SC) proliferation is unknown. To test the proliferative capacity of skeletal muscle SC in aging muscle to a potent mTORC1 activator (i.e., EAA; essential amino acids) we recruited older (~72y) men to conduct leg resistance exercise (8setsx10reps) without (-EAA; n = 8) and with (+EAA: n = 11) ingestion of 10 g of EAA 1 h postexercise...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28595260/kif15-promotes-pancreatic-cancer-proliferation-via-the-mek-erk-signalling-pathway
#7
Jie Wang, Xingjun Guo, Chencheng Xie, Jianxin Jiang
BACKGROUND: Pancreatic cancer is highly malignant and characterised by rapid and uncontrolled growth. While some of the important regulatory networks involved in pancreatic cancer have been determined, the cancer relevant genes have not been fully identified. METHODS: We screened genes that may control proliferation in pancreatic cancer in seven pairs of matched pancreatic cancer and normal pancreatic tissue samples. We examined KIF15 expression in pancreatic cancer tissues and the effect of KIF15 on cell proliferation in vitro and in vivo...
June 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28585698/lycopene-protects-keratinocytes-against-uvb-radiation-induced-carcinogenesis-via-negative-regulation-of-foxo3a-through-the-mtorc2-akt-signaling-pathway
#8
Ping Chen, Shina Xu, Jinlong Qu
Lycopene, one of the most potent anti-oxidants, has been reported to exhibit potent anti-proliferative properties in a wide range of cancer cells through modulation of the cell cycle and apoptosis. Forkhead box O3a (FOXO3a) plays a pivotal role in modulating the expression of genes involved in cell death. Herein, we investigated the role of FOXO3a signaling in the anti-cancer effects of lycopene. Results showed that lycopene pretreatment attenuated UVB-induced cell hyper-proliferation and promoted apoptosis, accompanied by decreased cyclin-dependent kinase 2 (CDK2) and CDK4 complex in both human keratinocytes and SKH-1 hairless mice...
June 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28582471/sumo-regulates-p21cip1-intracellular-distribution-and-with-p21cip1-facilitates-multiprotein-complex-formation-in-the-nucleolus-upon-dna-damage
#9
Sonia Brun, Neus Abella, Maria T Berciano, Olga Tapia, Montserrat Jaumot, Raimundo Freire, Miguel Lafarga, Neus Agell
We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs...
2017: PloS One
https://www.readbyqxmd.com/read/28578410/resveratrol-pretreatment-attenuates-concanavalin-a-induced-hepatitis-through-reverse-of-aberration-in-the-immune-response-and-regenerative-capacity-in-aged-mice
#10
Tse-Hung Huang, Chin-Chang Chen, Hsuan-Miao Liu, Tzung-Yan Lee, Sue-Heui Shieh
Loss of regenerative capacity plays a critical role in age-related autoimmune hepatitis. Evidence implicates SIRT1 and p66(shc) in cell senescence, apoptosis, oxidative stress, and proliferation. This study investigated the effect of resveratrol on concanavalin A (Con A)-induced hepatitis in aged mice and the roles of SIRT1 and p66(shc). Aged mice were administrated resveratrol (30 mg/kg orally) seven times at an interval of 12 h before a single intravenous injection of Con A (20 mg/kg). Results showed that the cytokines, TNF-α, IL-6, IFN-γ, and MCP-1, as well as infiltration of macrophages, neutrophils, and T lymphocytes in liver were dramatically enhanced in the mice given only Con A...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28575166/lta4h-regulates-cell-cycle-and-skin-carcinogenesis
#11
Naomi Oi, Hiroyuki Yamamoto, Alyssa Langfald, Ruihua Bai, Mee-Hyun Lee, Ann M Bode, Zigang Dong
Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model...
May 31, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28569402/lrwd1-regulates-microtubule-nucleation-and-proper-cell-cycle-progression-in-the-human-testicular-embryonic-carcinoma-cells
#12
Chia-Yih Wang, Yu-Han Hong, Jhih-Siang Syu, Yung-Chieh Tsai, Xiu-Ying Liu, Ting-Yu Chen, Yin-Mei Su, Pao-Lin Kuo, Yung-Ming Lin, Yen-Ni Teng
Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis-specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail...
June 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28566468/smad7-protects-against-acute-kidney-injury-by-rescuing-tubular-epithelial-cells-from-the-g1-cell-cycle-arrest
#13
Sha Fu, Ying Tang, Xiao Ru Huang, Min Feng, Anping Xu, Hui Y Lan
Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28555064/induction-of-p53-independent-apoptosis-and-g1-cell-cycle-arrest-by-fucoidan-in-hct116-human-colorectal-carcinoma-cells
#14
Hye Young Park, Shin-Hyung Park, Jin-Woo Jeong, Dahye Yoon, Min Ho Han, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Do-Hyung Kim, Gi-Young Kim, Il-Whan Choi, Suhkmann Kim, Heui-Soo Kim, Hee-Jae Cha, Yung Hyun Choi
It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53-/-) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines...
May 30, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#15
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539972/site-specific-regulation-of-histone-h1-phosphorylation-in-pluripotent-cell-differentiation
#16
Ruiqi Liao, Craig A Mizzen
BACKGROUND: Structural variation among histone H1 variants confers distinct modes of chromatin binding that are important for differential regulation of chromatin condensation, gene expression and other processes. Changes in the expression and genomic distributions of H1 variants during cell differentiation appear to contribute to phenotypic differences between cell types, but few details are known about the roles of individual H1 variants and the significance of their disparate capacities for phosphorylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28537766/pirfenidone-induces-g1-arrest-in-human-tenon-s-fibroblasts-in-vitro-involving-akt-and-mapk-signaling-pathways
#17
Xiujuan Guo, Yangfan Yang, Liling Liu, Xiaoan Liu, Jiangang Xu, Kaili Wu, Minbin Yu
PURPOSE: To investigate the underlying mechanism by which pirfenidone blocks the transition from the G1 to S phase in primary human Tenon's fibroblasts. METHODS: Primary human Tenon's fibroblasts were characterized by immunocytofluorescence staining with vimentin, fibroblast surface protein, and cytokeratin. After treating Tenon's fibroblasts with pirfenidone under proliferation conditions (10% fetal bovine serum), cell proliferation was measured using a WST-1 assay...
June 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28533114/2-aminomethylthieno-3-2-d-pyrimidin-4-3h-ones-bearing-3-methylpyrazole-hinge-binding-moiety-highly-potent-selective-and-time-dependent-inhibitors-of-cdc7-kinase
#18
Osamu Kurasawa, Misaki Homma, Yuya Oguro, Tohru Miyazaki, Kouji Mori, Noriko Uchiyama, Kenichi Iwai, Akihiro Ohashi, Hideto Hara, Sei Yoshida, Nobuo Cho
In order to increase the success rate for developing new Cdc7 inhibitors for cancer therapy, we explored a new chemotype which can comply with the previously-constructed pharmacophore model. Substitution of a pyridine ring of a serendipitously-identified Cdc7 inhibitor 2b with a 3-methylpyrazole resulted in a 4-fold increase in potency and acceptable kinase selectivity, leading to the identification of thieno[3,2-d]pyrimidin-4(3H)-one as an alternative scaffold. Structure-activity relationship (SAR) study revealed that incorporation of a substituted aminomethyl group into the 2-position improved kinase selectivity...
May 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28521470/new-role-of-human-ribosomal-protein-s3-regulation-of-cell-cycle-via-phosphorylation-by-cyclin-dependent-kinase-2
#19
Se Hee Han, Ji Hyung Chung, Joon Kim, Key-Sun Kim, Ye Sun Han
Human ribosomal protein S3 (hRpS3) is a component of the 40S ribosomal subunit that associated in protein synthesis. hRpS3 has additional ribosomal functions such as DNA repair, transcription, metastasis, and apoptosis via interaction with numerous signaling molecules and has different modifications. Cyclin-dependent kinases (CDKs) are heterodimeric serine/threonine protein kinases that regulate cell cycle progression. Among its members, the Cdk1-cyclin B complex is known to control cell progression in the G2/M phase, while Cdk2-cyclin E/A complexes function in G1/S and S/G2 transition...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520165/targeting-ccl4-induced-liver-fibrosis-by-rna-interference-mediated-inhibition-of-cyclin-e1-in-mice
#20
Jörg-Martin Bangen, Linda Hammerich, Roland Sonntag, Maike Baues, Ute Haas, Daniela Lambertz, Thomas Longerich, Twan Lammers, Frank Tacke, Christian Trautwein, Christian Liedtke
Initiation and progression of liver fibrosis requires proliferation and activation of resting hepatic stellate cells (HSC). Cyclin E1 (CcnE1) is the regulatory subunit of the Cyclin-dependent Kinase 2 (Cdk2) and controls cell cycle re-entry. We have recently shown that genetic inactivation of CcnE1 prevents activation, proliferation and survival of HSC and protects from liver fibrogenesis. The aim of the present study was to translate these findings into pre-clinical applications using an RNAi-based approach...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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