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https://www.readbyqxmd.com/read/28938642/facile-total-synthesis-of-lysicamine-and-the-anticancer-activities-of-the-ru-ii-rh-iii-mn-ii-and-zn-ii-complexes-of-lysicamine
#1
Jiao-Lan Qin, Ting Meng, Zhen-Feng Chen, Xiao-Li Xie, Qi-Pin Qin, Xiao-Ju He, Ke-Bin Huang, Hong Liang
Lysicamine is a natural oxoaporphine alkaloid, which isolated from traditional Chinese medicine (TCM) herbs and has been shown to possess cytotoxicity to hepatocarcinoma cell lines. Reports on its antitumor activity are scarce because lysicamine occurs in plants at a low content. In this work, we demonstrate a facile concise total synthesis of lysicamine from simple raw materials under mild reaction conditions, and the preparation of the Ru(II), Rh(III), Mn(II) and Zn(II) complexes 1-4 of lysicamine (LY). All the compounds were fully characterized by elemental analysis, IR, ESI-MS, (1)H and (13)C NMR, as well as single-crystal X-ray diffraction analysis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938528/p53-independent-p21-induction-by-melk-inhibition
#2
Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura, Jae-Hyun Park
MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938412/renal-metabolic-programming-is-linked-to-the-dynamic-regulation-of-a-leptin-klf15-axis-and-akt-ampk%C3%AE-signaling-in-male-offspring-of-obese-dams
#3
Philipp Kasper, Christina Vohlen, Katharina Dinger, Jasmine Mohr, Eva Hucklenbruch-Rother, Ruth Janoschek, Jessica Köth, Jan Matthes, Sarah Appel, Jörg Dötsch, Miguel A Alejandre Alcazar
Childhood obesity is associated with renal diseases. Maternal obesity is a risk factor linked to increased adipocytokines and metabolic disorders in the offspring. We therefore studied the impact of maternal obesity on renal-intrinsic insulin and adipocytokine signaling and on renal function and structure. To induce maternal obesity female mice were fed with high-fat diet (HFD) or standard diet (SD, Co) prior to mating, during gestation and throughout lactation. A third group of dams was fed HFD only during lactation (HFD-Lac)...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938245/gallic-acid-induces-g1-phase-arrest-and-apoptosis-of-triple-negative-breast-cancer-cell-mda-mb-231-via-p38-mitogen-activated-protein-kinase-p21-p27-axis
#4
Hsiang-Lin Lee, Chun-Shiang Lin, Shao-Hsuan Kao, Ming-Chih Chou
Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F...
September 21, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28937835/protective-effect-of-sulforaphane-against-retinal-degeneration-in-the-pde6-rd10-mouse-model-of-retinitis-pigmentosa
#5
Kai Kang, Minzhong Yu
PURPOSE: Retinitis pigmentosa (RP) is a group of inherited diseases characterized by the death of rod photoreceptors, followed by the death of cone photoreceptors, progressively leading to partial or complete blindness. Currently no specific treatment is available for RP patients. Sulforaphane (SFN) has been confirmed to be an effective antioxidant in the treatment of many diseases. In this study, we tested the therapeutic effects of SFN against photoreceptor degeneration in Pde6b(rd10) mice...
September 22, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28936683/trail-enhances-quinacrine-mediated-apoptosis-in-breast-cancer-cells-through-induction-of-autophagy-via-modulation-of-p21-and-dr5-interactions
#6
Sarita Das, Anmada Nayak, Sumit Siddharth, Deepika Nayak, Satya Narayan, Chanakya Nath Kundu
PURPOSE: Previously, we reported that quinacrine (QC) may cause apoptosis in breast and colon cancer cells by activating the death receptor 5 (DR5), resulting in autophagic cell death through p21 modulation. Here, we systematically evaluated the combined role of p21 and DR5 and their crosstalk in QC-mediated autophagy and apoptosis in breast cancer cells using in vitro and in vivo models. METHODS: Multiple breast cancer-derived cell lines (MCF-7, ZR-75-1, T47D, MDA-MB-231 and MCF-10A-Tr) and a mouse xenograft model were used...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28935368/ube2t-promotes-hepatocellular-carcinoma-cell-growth-via-ubiquitination-of-p53
#7
Li-Ping Liu, Mei Yang, Quan-Zhou Peng, Ming-Yue Li, Yu-Sen Zhang, Yue-Hua Guo, Yang Chen, Shi-Yun Bao
Deregulation of Ubiquitin-conjugating enzyme E2T (UBE2T) contributes to the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unclear. Here, we show that UBE2T is up-regulated in HCC and exerts oncogenic activities via ubiquitination of p53. High UBE2T expression was correlated with higher pathological grade, advanced TNM stage, tumor vascular invasion, and poor overall and disease-free survivals in two independent cohorts containing 827 patients with HCC...
September 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28934742/elevated-apoptosis-in-the-liver-of-dairy-cows-with-ketosis
#8
Xiliang Du, Liang Chen, Dan Huang, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Yiwei Zhu, Zhe Wang, Xinwei Li, Guowen Liu
BACKGROUND/AIMS: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. METHODS: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28932458/kinas2o7-a-new-diarsenate-with-the-tlinas2o7-structure-type
#9
Karolina Schwendtner, Uwe Kolitsch
Potassium indium diarsenate(V) was grown under mild hydro-thermal conditions (T = 493 K, 7 d) at a pH value of about 1. It adopts the TlInAs2O7 structure type (P-1, Z = 4) and is closely related to the KAlP2O7 (P21/c) and RbAlAs2O7 (P-1) structure types. The framework topology of KInAs2O7 is built of two symmetrically non-equivalent As2O7 groups which share corners with InO6 octa-hedra. The K atoms are located in channels extending along [010].
September 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28932448/a-temperature-dependent-phase-transformation-of-e-2-4-chloro-phen-yl-imino-ace-naphthylen-1-one
#10
Lipiao Bao, Marilyn M Olmstead
The crystal structure determination based on 90 K data of the title imine ligand, C18H10ClNO, revealed non-merohedral twinning with three twin domains. In our experience, this is an indication of an ordering phase transition. Consequently, the structure was redetermined with higher temperature data, and a reversible phase transition was discovered. The higher temperature phase is indeed an ordered structure. At the higher temperature, the 4-chloro-phenyl group has rotated by ca 7° into a crystallographic mirror plane...
July 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28932427/polymorphism-in-the-structure-of-n-5-methyl-thia-zol-2-yl-4-oxo-4h-chromene-3-carboxamide
#11
Ligia R Gomes, John Nicolson Low, Fernando Cagide, Fernanda Borges
Chromone derivatives have been extensively studied recently because of to their promising biological activities. The new title chromone-thia-zole hybrid presented here, C14H10N2O3S, is a candidate as a selective ligand for adenosine receptors. The compound has been synthesized and characterized by the usual spectroscopic means (NMR and EM/IE) and its structure elucidated by X-ray crystallography, which revealed the presence of packing polymorphism. The two polymorphs (one with space group P21/n and one with P21/c) show slightly different conformations and the major change induced by crystallization regards the intra-molecular contacts defining the supra-molecular structure...
July 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28931864/lymphoblastoid-cell-lines-from-diamond-blackfan-anaemia-patients-exhibit-a-full-ribosomal-stress-phenotype-that-is-rescued-by-gene-therapy
#12
Anna Aspesi, Valentina Monteleone, Marta Betti, Chiara Actis, Giulia Morleo, Marika Sculco, Simonetta Guarrera, Marcin W Wlodarski, Ugo Ramenghi, Claudio Santoro, Steven R Ellis, Fabrizio Loreni, Antonia Follenzi, Irma Dianzani
Diamond Blackfan anaemia (DBA) is a congenital bone marrow failure syndrome characterised by selective red cell hypoplasia. DBA is most often due to heterozygous mutations in ribosomal protein (RP) genes that lead to defects in ribosome biogenesis and function and result in ribosomal stress and p53 activation. The molecular mechanisms underlying this pathology are still poorly understood and studies on patient erythroid cells are hampered by their paucity. Here we report that RP-mutated lymphoblastoid cell lines (LCLs) established from DBA patients show defective rRNA processing and ribosomal stress features such as reduced proliferation, decreased protein synthesis, and activation of p53 and its target p21...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931685/p21-restricts-hiv-1-in-monocyte-derived-dendritic-cells-through-the-reduction-of-dntp-biosynthesis-and-regulation-of-samhd1-antiviral-activity
#13
Jose Carlos Valle-Casuso, Awatef Allouch, Annie David, Gina M Lenzi, Lydia Studdard, Françoise Barré-Sinoussi, Michaela Müller-Trutwin, Baek Kim, Gianfranco Pancino, Asier Sáez-Cirión
HIV-1 infection of non-cycling cells, such as dendritic cells (DCs), is impaired due to limited availability of dNTPs, which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during cell cycle and depend on the balance between dNTPs biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear. SAMHD1 has been reported to be able to degrade dNTPs and viral nucleic acids, which may both hamper HIV-1 reverse transcription...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28931551/endoplasmic-reticulum-membrane-protein-complex-subunit-10-emc10-is-a-bone-marrow-derived-angiogenic-growth-factor-promoting-tissue-repair-after-myocardial-infarction
#14
Marc R Reboll, Mortimer Korf-Klingebiel, Stefanie Klede, Felix Polten, Eva Brinkmann, Ines Reimann, Hans-Joachim Schönfeld, Maria Bobadilla, Jan Faix, George Kensah, Ina Gruh, Michael Klintschar, Matthias Gaestel, Hans W Niessen, Andreas Pich, Johann Bauersachs, Joseph A Gogos, Yong Wang, Kai C Wollert
Background -Clinical trials of bone marrow cell (BMC)-based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific BMC-derived secreted proteins may provide an alternative biologic approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in BMCs from patients with acute MI and discovered a poorly characterized secreted protein, endoplasmic reticulum membrane protein complex subunit 10 (EMC10), showing activity in an angiogenic screen...
September 20, 2017: Circulation
https://www.readbyqxmd.com/read/28931215/berberine-could-inhibit-thyroid-carcinoma-cells-by-inducing-mitochondrial-apoptosis-g0-g1-cell-cycle-arrest-and-suppressing-migration-via-pi3k-akt-and-mapk-signaling-pathways
#15
Liang Li, Xingchun Wang, Rampersad Sharvan, Jingyang Gao, Shen Qu
Berberine, an important natural isoquinoline alkaloid from traditional Chinese medicine, is reported to exhibit multiple pharmacological properties, including anti-microbial, anti-diabetes, anti-obesity, anti-inflammatory and anti-carcinogenic activities. Although studies have shown that a wide range of carcinoma cells could be inhibited by berberine, few studies involved thyroid carcinoma. We therefore examined the effect of berberine on papillary thyroid carcinoma (PTC, the most common subtype) and anaplastic thyroid carcinoma (ATC, the most malignant and aggressive subtype)...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28931042/evaluation-of-the-cytotoxicity-of-the-bithionol-paclitaxel-combination-in-a-panel-of-human-ovarian-cancer-cell-lines
#16
Vijayalakshmi N Ayyagari, Paula L Diaz-Sylvester, Tsung-Han Jeff Hsieh, Laurent Brard
Previously, Bithionol (BT) was shown to enhance the chemosensitivity of ovarian cancer cell lines to cisplatin treatment. In the present study, we focused on the anti-tumor potential of the BT-paclitaxel combination when added to a panel of ovarian cancer cell lines. This in vitro study aimed to 1) determine the optimum schedule for combination of BT and paclitaxel and 2) assess the nature and mechanism(s) underlying BT-paclitaxel interactions. The cytotoxic effects of both drugs either alone or in combination were assessed by presto-blue cell viability assay using six human ovarian cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28930680/systematic-kinase-inhibitor-profiling-identifies-cdk9-as-a-synthetic-lethal-target-in-nut-midline-carcinoma
#17
Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz, Peter Habenberger, Zhizhou Fang, Sandra Ortiz-Cuaran, Frauke Leenders, Jan Eickhoff, Uwe Koch, Matthäus Getlik, Martin Termathe, Muhammad Sallouh, Zoltán Greff, Zoltán Varga, Hyatt Balke-Want, Christopher A French, Martin Peifer, H Christian Reinhardt, László Örfi, György Kéri, Sascha Ansén, Lukas C Heukamp, Reinhard Büttner, Daniel Rauh, Bert M Klebl, Roman K Thomas, Martin L Sos
Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28928900/dihydroorotate-dehydrogenase-inhibitors-target-c-myc-and-arrest-melanoma-myeloma-and-lymphoma-cells-at-s-phase
#18
Mathura Subangari Dorasamy, Bhavesh Choudhary, Kavitha Nellore, Hosahalli Subramanya, Pooi-Fong Wong
Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase. Transfection with DHODH shRNA depleted DHODH protein expression and impeded the proliferation of melanoma cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928639/microglia-polarization-with-m1-m2-phenotype-changes-in-rd1-mouse-model-of-retinal-degeneration
#19
Tian Zhou, Zijing Huang, Xiaowei Sun, Xiaowei Zhu, Lingli Zhou, Mei Li, Bing Cheng, Xialin Liu, Chang He
Microglia activation is recognized as the hallmark of neuroinflammation. However, the activation profile and phenotype changes of microglia during the process of retinal degeneration are poorly understood. This study aimed to elucidate the time-spatial pattern of microglia distribution and characterize the polarized phenotype of activated microglia during retinal neuroinflammation and degeneration in rd1 (Pde6β(rd1/rd1)) mice, the classic model of inherited retinal degeneration. Retinae of rd1 mice at different postnatal days (P7, P14, P21, P28, P56, and P180) were prepared for further analysis...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28928376/oligo-fucoidan-prevents-il-6-and-ccl2-production-and-cooperates-with-p53-to-suppress-atm-signaling-and-tumor-progression
#20
Li-Mei Chen, Po-Yen Liu, Yen-An Chen, Hong-Yu Tseng, Pei-Chun Shen, Pai-An Hwang, Hsin-Ling Hsu
Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53(+/+)) or without (p53(-/-)) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks...
September 19, 2017: Scientific Reports
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