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https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#1
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#2
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28806684/photochemical-inactivation-of-lymphocytes-by-riboflavin-with-visible-light-for-ta-gvhd-prevention
#3
Qin Mo, Yuwen Huang, Li Wang, Zhenzhen Cheng, Xiaofei Wu, Yao Jia, Xun Wang, Bo Zhang
Transfusion-associated graft-versus-host disease (TA-GVHD) is a life-threatening complication caused by the input of a number of immunocompetent allogeneic lymphocytes. This study focus on the photochemical effects of riboflavin excited by visible light (RB+L) treatment on human lymphocytes, to study the feasibility of using RB+L treatment to prevent adverse immune reactions caused by transfused lymphocytes. 100μM riboflavin was added to lymphocyte suspensions. After exposure to 400-580nm visible light with a total energy of 40J/mL, cells were cultured and the ability of proliferation and cytokine secretion were assayed upon stimuli...
August 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28806647/mechanical-reinforcement-of-bioceramics-scaffolds-via-fracture-energy-dissipation-induced-by-sliding-action-of-mos2-nanoplatelets
#4
Cijun Shuai, Hang Sun, Chengde Gao, Pei Feng, Wang Guo, Youwen Yang, Mingchun Zhao, Sheng Yang, Fulai Yuan, Shuping Peng
The inherent brittleness of bioceramics restricts their applications in load bearing implant, although they possess good biocompatibility and bioactivity. In this study, molybdenum disulfide nanoplatelets (MSNPs) were used to reinforce bioceramics (Mg2SiO4/CaSiO3) scaffolds fabricated by selective laser sintering (SLS). The fracture mode of scaffolds was transformed from transgranular to mixed trans- and intergranular. It could be explained that MSNPs could slide easily due to their weak interlayer van der Waals interactions and provide elastic deformation due to their high elastic modulus...
July 20, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28806624/bcl-2-bax-protein-and-mrna-expression-in-yak-bos-grunniens-placentomes
#5
JiangFeng Fan, SiJiu Yu, Yan Cui, Gengquan Xu, Libin Wang, Yangyang Pan, Honghong He
Placental function is complex and influenced by various factors; furthermore, it depends on a delicate balance between cell proliferation, cell differentiation, and cell death. Bcl-2 and Bax proteins are key apoptosis regulators and are considered to play an important role in the maintenance of both dynamic balance and integrity of many tissues. Changes in Bcl-2 and Bax expressions have been described during different developmental stages in normal human placentas. Studies furthermore indicated several pathological placental changes to be related to abnormal Bcl-2 and Bax expressions...
July 29, 2017: Theriogenology
https://www.readbyqxmd.com/read/28806504/designing-liposomes-to-suppress-extracellular-matrix-expression-to-enhance-drug-penetration-and-pancreatic-tumor-therapy
#6
Tianjiao Ji, Jiayan Lang, Jing Wang, Rong Cai, Yinlong Zhang, Feifei Qi, Lijing Zhang, Xiao Zhao, Wenjing Wu, Jihui Hao, Zhihai Qin, Ying Zhao, Guangjun Nie
During pancreatic tumor development, pancreatic stellate cells (PSCs) proliferate exuberantly to secrete extracellular matrix (ECM) in the tumor stroma, which presents major barriers for drug delivery and penetration in tumor tissue. Thus, down-regulating ECM levels via regulation of the PSCs may allow enhanced penetration of therapeutic drugs and thereby enhancing their therapeutic efficacy. To regulate the PSCs, a matrix metalloproteinase-2 (MMP-2) responsive peptide-hybrid liposome (MRPL) was constructed via co-assembly of a tailor-designed MMP-2 responsive amphiphilic peptide and phospholipids...
August 14, 2017: ACS Nano
https://www.readbyqxmd.com/read/28806488/serotonergic-5-ht2b-receptors-in-mitral-valvulopathy-bone-marrow-mobilization-of-endothelial-progenitors
#7
Estelle Ayme-Dietrich, Roland Lawson, Francine Côté, Claudia de Tapia, Sylvia Da Silva, Claudine Ebel, Béatrice Hechler, Christian Gachet, Jérome Guyonnet, Hélène Rouillard, Jordane Stoltz, Emily Quentin, Sophie Banas, François Daubeuf, Nelly Frossard, Bernard Gasser, Jean-Philippe Mazzucotelli, Olivier Hermine, Luc Maroteaux, Laurent Monassier
BACKGROUND: Valvular heart disease is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the serotonin system has been associated with valvular heart disease. PURPOSE AND EXPERIMENTAL APPROACH: Here, we investigated the contribution of serotonin receptors in a mouse model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens dexfenfluramine and benfluorex. KEY RESULTS: Chronically activated 5-HT2B receptors by nordexfenfluramine in mice mimicked early steps of mitral valve remodelling attested by increased valve thickness, and cell density in a thick extracellular matrix...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28806447/homocysteine-facilitates-prominent-polygonal-angiogenetic-networks-of-a-choroidal-capillary-sprouting-model
#8
Yih-Jing Lee, Chien-Chao Chiu, Chia-Ying Ke, Ni Tien, Po-Kang Lin
Purpose: To investigate the effects of homocysteine on choroidal angiogenesis, we established an ex vivo choroidal sprouting explant model and examined the potential growth factors for angiogenesis. Methods: Choroid fragments with retinal pigment epithelium were isolated from mouse and embedded in Matrigel. Homocysteine at different concentrations were added to the culture mediums. The choroidal explants were observed at different time points, and the total area of choroidal sprouting was measured and analyzed...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28806396/inhibiting-myc-binding-to-the-e-box-dna-motif-by-me47-decreases-tumour-xenograft-growth
#9
L C Lustig, D Dingar, W B Tu, C Lourenco, M Kalkat, I Inamoto, R Ponzielli, W C W Chan, J A Shin, L Z Penn
Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50% of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806394/smggds-is-a-transient-nucleolar-protein-that-protects-cells-from-nucleolar-stress-and-promotes-the-cell-cycle-by-regulating-dream-complex-gene-expression
#10
P Gonyo, C Bergom, A C Brandt, S-W Tsaih, Y Sun, T M Bigley, E L Lorimer, S S Terhune, H Rui, M J Flister, R M Long, C L Williams
The chaperone protein and guanine nucleotide exchange factor SmgGDS (RAP1GDS1) is a key promoter of cancer cell proliferation and tumorigenesis. SmgGDS undergoes nucleocytoplasmic shuttling, suggesting that it has both cytoplasmic and nuclear functions that promote cancer. Previous studies indicate that SmgGDS binds cytoplasmic small GTPases and promotes their trafficking to the plasma membrane. In contrast, little is known about the functions of SmgGDS in the nucleus, or how these nuclear functions might benefit cancer cells...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806271/luminal-chemosensing-in-the-gastroduodenal-mucosa
#11
Izumi Kaji, Jonathan D Kaunitz
PURPOSE OF REVIEW: We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa. RECENT FINDINGS: Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation...
August 12, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28806136/harnessing-olig2-function-in-tumorigenicity-and-plasticity-to-target-malignant-gliomas
#12
Jennifer Kosty, Fanghui Lu, Robert Kupp, Shwetal Mehta, Q Richard Lu
Glioblastoma (GBM) is the most prevalent and malignant brain tumor, displaying notorious resistance to conventional therapy, partially due to molecular and genetic heterogeneity. Understanding the mechanisms for gliomagenesis, tumor stem/progenitor cell propagation and phenotypic diversity is critical for devising effective and targeted therapy for this lethal disease. The basic helix-loop-helix transcription factor OLIG2, which is universally expressed in gliomas, has emerged as an important player in GBM cell reprogramming, genotoxic resistance, and tumor phenotype plasticity...
August 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28805944/suppression-of-acute-and-anticipatory-nausea-by-peripherally-restricted-faah-inhibitor-in-animal-models-role-of-ppar%C3%AE-and-cb1-receptors
#13
Erin M Rock, Guillermo Moreno-Sanz, Cheryl L Limebeer, Gavin N Petrie, Roberto Angelini, Daniele Piomelli, Linda A Parker
To evaluate the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937 (cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) to suppress acute and anticipatory nausea in rats, and to examine the pharmacological mechanism of such an effect. EXPERIMENTAL APPROACH: We investigated the potential of URB937 to reduce the establishment of lithium chloride (LiCl)-induced conditioned gaping (a model of acute nausea) and to reduce the expression of contextually elicited conditioned gaping (a model of anticipatory nausea) in rats...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28805938/what-is-new-in-the-pathophysiology-of-acne-an-overview
#14
REVIEW
B Dréno
Acne is a chronic inflammatory disease of the pilosebaceous unit. Its pathophysiology includes hyperseborrhoea, abnormal follicular keratinization and Propionibacterium acnes proliferation in the pilosebaceous unit. Recent research has shed some new light on the involvement of the sebaceous gland, as well as on the pro-inflammatory activity of the cutaneous microbiome. During puberty, alteration of the sebaceous lipid profile, called dysseborrhoea, stress, irritation, cosmetics and potential dietary factors lead to inflammation and formation of different types of acne lesions...
September 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28805906/technical-note-induction-of-pluripotent-stem-cell-like-cells-from-chicken-feather-follicle-cells
#15
Y M Kim, Y H Park, J M Lim, H Jung, J Y Han
Pluripotent stem cells including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) are regarded as representative tools for conservation of animal genetic resources. Although ESC have been established from chicken, it is very difficult to obtain enough embryos for isolation of stem cells for avian conservation in most wild birds. Therefore, the high feasibility of obtaining the pluripotent cell is most important in avian conservation studies. In this study, we generated induced pluripotent stem cell-like cells (iPSLC) from avian Feather Follicular cells (FFC)...
August 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28805828/mutations-in-keops-complex-genes-cause-nephrotic-syndrome-with-primary-microcephaly
#16
Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt
Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue...
August 14, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28805807/notch-signaling-pathway-and-gene-expression-profiles-during-early-in-vitro-differentiation-of-liver-derived-mesenchymal-stromal-cells-to-osteoblasts
#17
Ksymena Urbanek, Marta Lesiak, Daniel Krakowian, Halina Koryciak-Komarska, Wirginia Likus, Piotr Czekaj, Damian Kusz, Aleksander L Sieroń
Notch signaling is a key signaling pathway for cell proliferation and differentiation. Therefore, we formulated a working hypothesis that Notch signaling can be used to detect early osteoblastic differentiation of mesenchymal stromal cells. Changes in expression and distribution of Notch 1, 2, 3, and Delta1 in the cytoplasm and nuclei of rat liver-derived mesenchymal stromal cells differentiating into osteoblasts were investigated, together with the displacement of intracellular domains (ICDs) of the receptors...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#18
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28805696/licochalcone-a-inhibits-the-proliferation-of-human-lung-cancer-cell-lines-a549-and-h460-by-inducing-g2-m-cell-cycle-arrest-and-er-stress
#19
Chenyu Qiu, Tingting Zhang, Wenxin Zhang, Lina Zhou, Bin Yu, Wei Wang, Zhihong Yang, Zhiguo Liu, Peng Zou, Guang Liang
Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased cell viability and induced apoptosis in a dose-dependent manner in NSCLC cells. LicA inhibited lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LicA treatment decreased the expression of MDM2, Cyclin B1, Cdc2 and Cdc25C in H460 and A549 cancer cell lines...
August 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28805694/progenitor-cells-from-cartilage-grade-specific-differences-in-stem-cell-marker-expression
#20
Marija Mazor, Annabelle Cesaro, Mazen Ali, Thomas M Best, Eric Lespessaille, Hechmi Toumi
Recent research has confirmed the presence of Mesenchymal stem cell (MSC)-like progenitors (MPC) in both normal and osteoarthritic cartilage. However, there is only limited information concerning how MPC markers are expressed with osteoarthritis (OA) progression. The purpose of this study was to compare the prevalence of various MPC markers in different OA grades. Human osteoarthritic tibial plateaus were obtained from ten patients undergoing total knee replacement. Each sample had been classified into a mild or severe group according to OARSI scoring...
August 12, 2017: International Journal of Molecular Sciences
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