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https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#1
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28432350/enhancing-the-throughput-and-multiplexing-capabilities-of-next-generation-sequencing-for-efficient-implementation-of-pooled-shrna-and-crispr-screens
#2
Md Fahmid Islam, Atsushi Watanabe, Lai Wong, Conor Lazarou, Frederick S Vizeacoumar, Omar Abuhussein, Wayne Hill, Maruti Uppalapati, C Ronald Geyer, Franco J Vizeacoumar
Next generation sequencing is becoming the method of choice for functional genomic studies that use pooled shRNA or CRISPR libraries. A key challenge in sequencing these mixed-oligo libraries is that they are highly susceptible to hairpin and/or heteroduplex formation. This results in polyclonal, low quality, and incomplete reads and reduces sequencing throughput. Unfortunately, this challenge is significantly magnified in low-to-medium throughput bench-top sequencers as failed reads significantly perturb the maximization of sequence coverage and multiplexing capabilities...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431926/multiple-repair-pathways-mediate-cellular-tolerance-to-resveratrol-induced-dna-damage
#3
Ying Liu, Xiaohua Wu, Xiaoqing Hu, Ziyuan Chen, Hao Liu, Shunichi Takeda, Yong Qing
Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects...
April 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28431563/inheritance-of-brewing-relevant-phenotypes-in-constructed-saccharomyces-cerevisiae%C3%A2-%C3%A3-%C3%A2-saccharomyces-eubayanus-hybrids
#4
Kristoffer Krogerus, Tuulikki Seppänen-Laakso, Sandra Castillo, Brian Gibson
BACKGROUND: Interspecific hybridization has proven to be a potentially valuable technique for generating de novo lager yeast strains that possess diverse and improved traits compared to their parent strains. To further enhance the value of hybridization for strain development, it would be desirable to combine phenotypic traits from more than two parent strains, as well as remove unwanted traits from hybrids. One such trait, that has limited the industrial use of de novo lager yeast hybrids, is their inherent tendency to produce phenolic off-flavours; an undesirable trait inherited from the Saccharomyces eubayanus parent...
April 21, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#5
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431380/recent-aspects-of-uranium-toxicology-in-medical-geology
#6
REVIEW
Geir Bjørklund, Olav Albert Christophersen, Salvatore Chirumbolo, Olle Selinus, Jan Aaseth
Uranium (U) is a chemo-toxic, radiotoxic and even a carcinogenic element. Due to its radioactivity, the effects of U on humans health have been extensively investigated. Prolonged U exposure may cause kidney disease and cancer. The geological distribution of U radionuclides is still a great concern for human health. Uranium in groundwater, frequently used as drinking water, and general environmental pollution with U raise concerns about the potential public health problem in several areas of Asia. The particular paleo-geological hallmark of India and other Southern Asiatic regions enhances the risk of U pollution in rural and urban communities...
April 18, 2017: Environmental Research
https://www.readbyqxmd.com/read/28430414/dynamic-and-energetic-signatures-of-adenine-tracts-in-a-ra-dt-rna-dna-hybrid-and-in-homologous-rna-dna-rna-rna-and-dna-dna-double-helices
#7
Yuegao Huang, Irina M Russu
Nuclear magnetic resonance spectroscopy and proton exchange are being used to characterize the opening reactions of individual base pairs in the RNA-DNA hybrid 5'-rGCGAUAAAAAGGCC-3'/5'-dGGCCTTTTTATCGC-3'. The hybrid contains a central tract of five rA-dT base pairs. The rates and the equilibrium constant of the opening reaction for each base pair are determined from the dependence of the exchange rates of imino protons on ammonia concentration, at 10°C. The results are compared to those previously obtained by our laboratory for three homologous duplexes of the same base sequence (except for the appropriate T/U substitution), containing tracts of dA-rU, rA-rU or dA-dT base pairs...
April 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28430183/neuroprotectin-d1-upregulates-iduna-expression-and-provides-protection-in-cellular-uncompensated-oxidative-stress-and-in-experimental-ischemic-stroke
#8
Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong, Nicolas G Bazan
Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28430157/development-of-user-friendly-method-to-distinguish-subspecies-of-the-korean-medicinal-herb-perilla-frutescens-using-multiplex-pcr
#9
Yonguk Kim, Ah-Young Kim, Ara Jo, Hakjoon Choi, Seung-Sik Cho, Chulyung Choi
Perilla (Perilla frutescens) is an economically and culturally important plant in East Asia. Plant breeding between cultivars has enhanced the genetic diversity of perilla overall, but means that functionally diverse subspecies are more difficult to identify and distinguish. In this study, we developed gene-based DNA markers to distinguish between the Korean herbal medicinal perilla varieties. We identified informative simple sequence repeat (SSR) regions on the promoter regions of the Myb-P1 and dihydroflavonol 4-reductase (DFR) genes, as well as a large insertion-deletion (indel) region in the limonene synthase (LS) gene, and developed markers to characterize the distinct subspecies differences (PfMyb-P1pro, PfDFRpro, and PfLS, respectively)...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28429680/the-inhibitory-effects-of-hydamtiq-a-novel-parp-inhibitor-on-growth-in-human-tumor-cell-lines-with-defective-dna-damage-response-pathways
#10
Enrico Mini, Ida Landini, Laura Lucarini, Andrea Lapucci, Cristina Napoli, Gabriele Perrone, Renato Tassi, Emanuela Masini, Flavio Moroni, Stefania Nobili
The poly(ADP-ribose) polymerase (PARP) enzymes play key roles in the regulation of cellular processes (e.g. DNA damagerepair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells with dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP1 activity.The aim of this study was to evaluate the growth inhibitory effects of a novel PARPI, HYDAMTIQ, on human tumor cell lines characterized by different features with regard to DNA damage response pathways (BRCA mutational status, microsatellite status and ATM expression level) and degree of sensitivity/resistance to 5-fluorouracil...
April 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28429586/bubble-mediated-ultrasensitive-multiplex-detection-of-metal-ions-in-three-dimensional-dna-nanostructure-encoded-microchannels
#11
Xiangmeng Qu, Fan Yang, Hong Chen, Jiang Li, Hongbo Zhang, Guo-Jun Zhang, Li Li, Lihua Wang, Shiping Song, Yang Tian, Hao Pei
The development of rapid and sensitive point-of-test devices for the on-site monitoring of heavy-metal contamination has great scientific and technological importance. However, developing fast, inexpensive, and sensitive microarray sensors to achieve such goal remains challenging. In this work, we present a DNA nanostructured microarray (DNM) with tubular three-dimensional (3D) sensing surface and ordered nanotopography. This microarray enables enhanced molecular interaction toward the rapid and sensitive multiplex detection of heavy-metal ions...
April 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28429327/large-scale-cultivation-of-euglena
#12
Kengo Suzuki
From the middle of the twentieth century, microalgae have been exploited as a candidate biomass source of food and other products. One such candidate source is the fast-proliferating microalga Euglena gracilis. The commercial cultivation of E. gracilis began in 2007, after the success of its outdoor mass cultivation and improvement of the harvesting and drying methods suitable for Euglena cells. The commercialization of Euglena production is based on the strategy of "5Fs of Biomass," which refers to the development and production of commercial products including food, fiber, feed, fertilizer, and fuel from biomass...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28429234/neuron-to-neuron-transfer-of-fus-in-drosophila-primary-neuronal-culture-is-enhanced-by-als-associated-mutations
#13
Sébastien Feuillette, Morgane Delarue, Gaëtan Riou, Anne-Lise Gaffuri, Jane Wu, Zsolt Lenkei, Olivier Boyer, Thierry Frébourg, Dominique Campion, Magalie Lecourtois
The DNA- and RNA-binding protein fused in sarcoma (FUS) has been pathologically and genetically linked to amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Cytoplasmic FUS-positive inclusions were identified in the brain and spinal cord of a subset of patients suffering with ALS/FTLD. An increasing number of reports suggest that FUS protein can behave in a prion-like manner. However, no neuropathological studies or experimental data were available regarding cell-to-cell spread of these pathological protein assemblies...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#14
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28428341/ctf4-related-protein-recruits-lhp1-prc2-to-maintain-h3k27me3-levels-in-dividing-cells-in-arabidopsis-thaliana
#15
Yue Zhou, Emmanuel Tergemina, Haitao Cui, Alexander Förderer, Benjamin Hartwig, Geo Velikkakam James, Korbinian Schneeberger, Franziska Turck
Polycomb Repressive Complex (PRC) 2 catalyzes the H3K27me3 modification that warrants inheritance of a repressive chromatin structure during cell division, thereby assuring stable target gene repression in differentiated cells. It is still under investigation how H3K27me3 is passed on from maternal to filial strands during DNA replication; however, cell division can reinforce H3K27me3 coverage at target regions. To identify novel factors involved in the Polycomb pathway in plants, we performed a forward genetic screen for enhancers of the like heterochromatin protein 1 (lhp1) mutant, which shows relatively mild phenotypic alterations compared with other plant PRC mutants...
April 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28427701/multiple-sclerosis-showing-elevation-of-adenosine-deaminase-levels-in-the-cerebrospinal-fluid
#16
Miharu Samuraki, Kenji Sakai, Yasuko Odake, Mitsuhiro Yoshita, Kouichi Misaki, Mitsutoshi Nakada, Masahito Yamada
An 80-year-old man developed dysarthria, quadriplegia, sensory disturbance and ataxia in all limbs. Brain and spinal magnetic resonance imaging (MRI) revealed multiple enhanced lesions. Cerebrospinal fluid (CSF) levels of adenosine deaminase (ADA) remarkably elevated. Tuberculosis DNA was not detected, and tuberculosis was not cultured either in the CSF. Brain biopsy revealed the inflammatory demyelinating lesions. With the diagnosis of multiple sclerosis, corticosteroid therapy resulted in rapid improvement of his symptoms and MRI abnormalities...
April 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28427225/enhancing-synthetic-lethality-of-parp-inhibitor-and-cisplatin-in-brca-proficient-tumour-cells-with-hyperthermia
#17
Arlene L Oei, Caspar M van Leeuwen, Vidhula R Ahire, Hans M Rodermond, Rosemarie Ten Cate, Anneke M Westermann, Lukas J A Stalpers, Johannes Crezee, H Petra Kok, Przemek M Krawczyk, Roland Kanaar, Nicolaas A P Franken
BACKGROUND: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427182/identification-of-dbccr1-as-a-suppressor-in-the-development-of-lung-cancer-that-is-associated-with-increased-dna-methyltransferase-1
#18
Guoren Zhou, Jinjun Ye, Ying Fang, Zhi Zhang, Jingyuan Zhang, Lei Sun, Jifeng Feng
Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425971/%C3%AF-%C3%A2-cells-feature-de-ubiquitination-of-slc-transporters-and-increased-levels-and-fluxes-of-amino-acids
#19
André Bordinassi Medina, Marcin Banaszczak, Yang Ni, Ina Aretz, David Meierhofer
Solute carrier (SLC) transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs), such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ⁰ cells (lacking mitochondrial DNA, mtDNA) compared to parental cells...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425913/loss-of-dnmt3a-and-dnmt3b-does-not-affect-epidermal-homeostasis-but-promotes-squamous-transformation-through-ppar-%C3%AE
#20
Lorenzo Rinaldi, Alexandra Avgustinova, Mercé Martin, Debayan Datta, Guiomar Solanas, Neus Prats, Salvador Aznar Benitah
The DNA methyltransferase Dnmt3a suppresses tumorigenesis in models of leukemia and lung cancer. Conversely, deregulation of Dnmt3b is thought to generally promote tumorigenesis. However, the role of Dnmt3a and Dnmt3b in many types of cancer remains undefined. Here we show that Dnmt3a and Dnmt3b are dispensable for homeostasis of the murine epidermis. However, loss of Dnmt3a-but not Dnmt3b-increases the number of carcinogen-induced squamous tumors, without affecting tumor progression. Only upon combined deletion of Dnmt3a and Dnmt3b, squamous carcinomas become more aggressive and metastatic...
April 20, 2017: ELife
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