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https://www.readbyqxmd.com/read/28334702/in-vitro-antibacterial-activity-of-7-substituted-6-fluoroquinolone-and-7-substituted-6-8-difluoroquinolone-derivatives
#1
Socorro Leyva-Ramos, Denisse de Loera, Jaime Cardoso-Ortiz
BACKGROUND: Fluoroquinolones are widely prescribed synthetic antimicrobial agents. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome; the irreversible DNA damage eventually causes the killing of bacteria. Thorough knowledge of the structure-activity relationship of quinolones is essential for the development of new drugs with improved activity against resistant strains. METHODS: The compounds were screened for their antibacterial activity against 4 representing strains using the Kirby-Bauer disk diffusion method...
March 24, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28331416/dna-pk-inhibition-by-nu7441-enhances-chemosensitivity-to-topoisomerase-inhibitor-in-non-small-cell-lung-carcinoma-cells-by-blocking-dna-damage-repair
#2
Masaaki Yanai, Haruhiko Makino, Bingqiong Ping, Kenichi Takeda, Natsumi Tanaka, Tomohiro Sakamoto, Kosuke Yamaguchi, Masahiro Kodani, Akira Yamasaki, Tadashi Igishi, Eiji Shimizu
BACKGROUND: DNA double-strand breaks (DSBs) are the most cytotoxic form of DNA damage and are induced by ionizing radiation and specific chemotherapeutic agents, such as topoisomerase inhibitors. Cancer cells acquire resistance to such therapies by repairing DNA DSBs. A major pathway for the repair of DNA DSBs is non-homologous end-joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-PK on the chemosensitization of non-small cell lung carcinoma (NSCLC) A549 cells...
March 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28325498/the-role-of-rnase-h2-in-processing-ribonucleotides-incorporated-during-dna-replication
#3
Jessica S Williams, Daniel B Gehle, Thomas A Kunkel
Saccharomyces cerevisiae RNase H2 resolves RNA-DNA hybrids formed during transcription and it incises DNA at single ribonucleotides incorporated during nuclear DNA replication. To distinguish between the roles of these two activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ribonucleotides that are stably incorporated into the genome...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28324147/genotoxicity-kinetics-in-murine-normoblasts-as-an-approach-for-the-in-vivo-action-of-difluorodeoxycytidine
#4
Pedro Morales-Ramírez, Teresita Vallarino-Kelly, Virginia Cruz-Vallejo
PURPOSE: This study analyzed the kinetics of in vivo micronucleus induction in normoblasts by determining the kinetics of difluorodeoxycytidine (dFdC)-induced micronucleated polychromatic erythrocytes (MN-PCEs) in the peripheral blood of mice. The kinetic indexes of MN-PCE induction of dFdC were correlated with the previously reported mechanisms DNA damage induction by this compound. In general, this study aimed to establish an in vivo approach for discerning the processes underlying micronucleus induction by antineoplastic agents or mutagens in general...
March 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28303897/synergistic-efficacy-of-bisbenzimidazole-and-carbonyl-cyanide-3-chlorophenylhydrazone-combination-against-mdr-bacterial-strains
#5
Devapriya Sinha, Stuti Pandey, Raja Singh, Vinod Tiwari, Kirti Sad, Vibha Tandon
Activation of efflux systems and the formation of biofilm are majorly adapted by microbes to resist antimicrobial agents. PPEF (bisbenzimidazole) targeting topoisomerase IA is observed to be an effective bactericidal agent against both Gram-positive and Gram-negative bacterial strains and thus can be developed as potent broad-spectrum antibiotic against MDR strains. PPEF treatment did not cause target specific mutation instead it leads to up-regulation of efflux gene in E. coli K12 as a mechanism of resistance...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303361/human-topoisomerase-inhibition-and-dna-bsa-binding-of-ru-ii-scar-complexes-as-potential-anticancer-candidates-for-oral-application
#6
Rone A De Grandis, Mariana S de Camargo, Monize M da Silva, Érica O Lopes, Elias C Padilha, Flávia A Resende, Rosângela G Peccinini, Fernando R Pavan, Alessandro Desideri, Alzir A Batista, Eliana A Varanda
Three ruthenium(II) phosphine/diimine/picolinate complexes were selected aimed at investigating anticancer activity against several cancer cell lines and the capacity of inhibiting the supercoiled DNA relaxation mediated by human topoisomerase IB (Top 1). The structure-lipophilicity relationship in membrane permeability using the Caco-2 cells have also been evaluated in this study. SCAR 5 was found to present 45 times more cytotoxicity against breast cancer cell when compared to cisplatin. SCAR 4 and 5 were both found to be capable of inhibiting the supercoiled DNA relaxation mediated by Top 1...
March 16, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28302748/smc5-6-is-required-for-the-formation-of-segregation-competent-bivalent-chromosomes-during-meiosis-i-in-mouse-oocytes
#7
Grace Hwang, Fengyun Sun, Marilyn O'Brien, John J Eppig, Mary Ann Handel, Philip W Jordan
SMC complexes include three major classes: cohesin, condensin, and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis had not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre-driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis...
March 16, 2017: Development
https://www.readbyqxmd.com/read/28301542/dna-topoisomerase-ii%C3%AE-and-mitosin-expression-predict-meningioma-recurrence-better-than-histopathological-grade-and-mib-1-after-initial-surgery
#8
Theo L Winther, Sverre H Torp
BACKGROUND: The 2016 WHO histopathological grade or conventional biomarker MIB-1 is insufficient for predicting meningioma recurrence after initial treatment and alternative strategies are required. In this study, we investigated whether DNA topoisomerase IIα and/or mitosin expression can predict tumor recurrence with greater accuracy than conventional methods. METHODS: The expression of MIB-1, topoisomerase IIα, and mitosin were determined as proliferation indices in tissue microarrays using immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28299506/identification-of-the-ligand-of-pru-p-3-a-peach-ltp
#9
Nuria Cubells-Baeza, Cristina Gómez-Casado, Leticia Tordesillas, Carmen Ramírez-Castillejo, María Garrido-Arandia, Pablo González-Melendi, María Herrero, Luis F Pacios, Araceli Díaz-Perales
Pru p 3, a peach LTP, is located in pollinated flower styles and secreting downy hairs, transporting a derivative of camptothecin bound to phytosphingosine. Pru p 3 may inhibit a second pollination and may keep away herbivores until seed maturation. The allergen Pru p 3, a peach lipid transfer protein, has been well studied. However, its physiological function remains to be elucidated. Our results showed that Pru p 3 usually carries a lipid ligand that play an essential role in its function in plants. Using ESI-qToF, we observed that the ligand was a derivative of camptothecin binding to phytosphingosine, wich that is inserted into the hydrophobic tunnel of the protein...
March 15, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28296274/relevance-of-clinical-and-autoantibody-profiles-in-systemic-sclerosis-among-thais
#10
Chingching Foocharoen, Piyakarn Watcharenwong, Sittichai Netwijitpan, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Ratanavadee Nanagara
OBJECTIVE: Autoantibody profiles in systemic sclerosis (SSc) and their relative clinical association vary between studies. The rate for being anti-topoisomerase-I (ATA) positive and the association with diffuse cutaneous the SSc subset (dcSSc) is higher among Thais than among Caucasians. The objective was to evaluate the relevance of clinical presentation, namely being positive for one or more autoantibodies among Thai SSc patients. METHOD: A retrospective, cohort study was performed among SSc patients over 18 years of age at Srinagarind Hospital, Khon Kaen University, Thailand, during January 2006 to December 2013...
March 10, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28283779/phase-ib-study-of-the-mitochondrial-inhibitor-me-344-plus-topotecan-in-patients-with-previously-treated-locally-advanced-or-metastatic-small-cell-lung-ovarian-and-cervical-cancers
#11
Jennifer R Diamond, Barbara Goff, Martin D Forster, Johanna C Bendell, Carolyn D Britten, Michael S Gordon, Hani Gabra, David M Waterhouse, Mark Poole, D Ross Camidge, Erika Hamilton, Kathleen M Moore
Background This multicenter, open-label, phase Ib study was designed to assess the safety, pharmacokinetics and preliminary efficacy of ME-344, a mitochondrial inhibitor, administered in combination with the topoisomerase I inhibitor, topotecan, in patients with previously treated, locally advanced or metastatic small cell lung (SCLC), ovarian and cervical cancers. Patients and methods In Part 1, patients received ME-344 10 mg/kg intravenously weekly on days 1, 8, 15 and 22 in combination with topotecan 4 mg/m(2) on days 1, 8, and 15 of a 28 day cycle...
March 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28283390/functional-characterization-of-brassica-napus-dna-topoisomerase-i%C3%AE-1-and-its-effect-on-flowering-time-when-expressed-in-arabidopsis-thaliana
#12
Chenhao Gao, Shuanghui Qi, Kaige Liu, Dong Li, Changyu Jin, Shaowei Duan, Meng Zhang, Mingxun Chen
Previous studies have shown that DNA topoisomerase Iα (AtTOP1α) has specific developmental functions during growth and development in Arabidopsis thaliana. However, little is known about the roles of DNA topoisomerases in the closely related and commercially important plant, rapeseed (Brassica napus). Here, the full-length BnTOP1α-1 coding sequence was cloned from the A2 subgenome of the Brassica napus inbred line L111. We determine that all BnTOP1α paralogs showed differing patterns of expression in different organs of L111, and that when expressed in tobacco leaves as a fusion protein with green fluorescent protein, BnTOP1α-1 localized to the nucleus...
March 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28275243/the-microrna-expression-signature-of-small-cell-lung-cancer-tumor-suppressors-of-mir-27a-5p-and-mir-34b-3p-and-their-targeted-oncogenes
#13
Keiko Mizuno, Hiroko Mataki, Takayuki Arai, Atsushi Okato, Kazuto Kamikawaji, Tomohiro Kumamoto, Tsubasa Hiraki, Kazuhito Hatanaka, Hiromasa Inoue, Naohiko Seki
Small cell lung cancer (SCLC) constitutes approximately 15% of all diagnosed lung cancers. SCLC is a particularly lethal malignancy, as the 2-year survival rate after appropriate treatment is less than 5%. The patients with SCLC have not been received a benefit of the recently developed molecular targeted treatment. Therefore, a new treatment strategy is necessary for the patients. The molecular mechanisms underlying the aggressiveness of SCLC cells and their development of treatment-resistance are still ambiguous...
March 9, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28271673/mutations-in-dna-gyrase-and-topoisomerase-iv-in-ciprofloxacin-nonsusceptible-extended-spectrum-%C3%AF-lactamase-producing-escherichia-coli-and-klebsiella-pneumoniae
#14
Kyung Sun Park, Hyung-Seok Yang, You Sun Nam, Hee Joo Lee
BACKGROUND: We investigated mutations in the quinolone resistance-determining region (QRDR) of ciprofloxacinnonsusceptible extended-spectrum -lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae by a statistical analysis. METHODS: We collected 97 clinical isolates of ciprofloxacin-nonsusceptible ESBL-producing E. coli (55 strains) and K. pneumoniae (42 strains) from a tertiary-care university hospital in Seoul, Republic of Korea, between 2006 and 2008...
March 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28268090/both-r-loop-removal-and-ribonucleotide-excision-repair-activities-of-rnase-h2-contribute-substantially-to-chromosome-stability
#15
Deborah A Cornelio, Hailey N C Sedam, Jessica A Ferrarezi, Nadia M V Sampaio, Juan Lucas Argueso
Cells carrying deletions of genes encoding H-class ribonucleases display elevated rates of chromosome instability. The role of these enzymes is to remove RNA-DNA associations including persistent mRNA-DNA hybrids (R-loops) formed during transcription, and ribonucleotides incorporated into DNA during replication. RNases H1 and H2 can degrade the RNA component of R-loops, but only RNase H2 can initiate accurate ribonucleotide excision repair (RER). In order to examine the specific contributions of these activities to chromosome stability, we measured rates of loss-of-heterozygosity (LOH) in diploid Saccharomyces cerevisiae yeast strains carrying the rnh201-RED separation-of-function allele, encoding a version of RNase H2 that is RER-defective, but partly retains its other activity...
February 20, 2017: DNA Repair
https://www.readbyqxmd.com/read/28263964/total-rna-seq-to-identify-pharmacological-effects-on-specific-stages-of-mrna-synthesis
#16
Sarah A Boswell, Andrew Snavely, Heather M Landry, L Stirling Churchman, Jesse M Gray, Michael Springer
Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation...
March 6, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28262707/management-of-e-coli-sister-chromatid-cohesion-in-response-to-genotoxic-stress
#17
Elise Vickridge, Charlene Planchenault, Charlotte Cockram, Isabel Garcia Junceda, Olivier Espéli
Aberrant DNA replication is a major source of the mutations and chromosomal rearrangements associated with pathological disorders. In bacteria, several different DNA lesions are repaired by homologous recombination, a process that involves sister chromatid pairing. Previous work in Escherichia coli has demonstrated that sister chromatid interactions (SCIs) mediated by topological links termed precatenanes, are controlled by topoisomerase IV. In the present work, we demonstrate that during the repair of mitomycin C-induced lesions, topological links are rapidly substituted by an SOS-induced sister chromatid cohesion process involving the RecN protein...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28254521/biological-evaluation-of-a-halogenated-triterpenoid-2%C3%AE-bromo-dihydrobelulonic-acid-as-inhibitor-of-human-topoisomerase-ii%C3%AE-and-hela-cell-proliferation
#18
Shilpi Ghosh, Swagata Mukhopadhyay, Mrinmoy Sarkar, Amitava Mandal, Vaskar Das, Anoop Kumar, Biplab Giri
BACKGROUND: The pentacyclic lupane-type (6-6-6-6-5 type) triterpenoid, Betulinic acid (BA) is a potent inhibitor of topoisomerases and is of immense interest as anticancer drugs. However, the compound being highly lipophilic, has limited in vivo uptake capacity. BA derivatives with halogen substituent at C-2 have improved membrane permeability and cytotoxicity against cancer cells. AIM: The halogenated triterpenoid, 2α-bromo-dihydrobetulonic acid (B1) was synthesized from betulinic acid (BA) isolated from Bischofia javanica...
February 28, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28253714/microarray-expression-analysis-of-mycn-amplified-neuroblastoma-cells-after-inhibition-of-cdk2
#19
H Song, F Wu, S Li, Z Wang, X Liu, Y Cui, C Lin
The study was aimed to explore the underlying molecular mechanisms of CDK2 inhibition in neuroblastoma by bioinformatics analysis. Gene expression profile GSE16480 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified from IMR32 between each time point and average expression of all time points. Gene significance was calculated using dSVDsig algorithm of dnet package. Protein-protein interaction (PPI) network was built. Then, integrated with gene significance, a core PPI network was detected by dNetPipeline algorithm in dnet package...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28250789/cestrum-nocturnum-flower-extracts-attenuate-proliferation-and-induce-apoptosis-in-malignant-cells-through-inducing-dna-damage-and-inhibiting-topoisomerase-ii-activity
#20
Deng-Pan Wu, Tian-Yu Lin, Jin-Yan Lv, Wen-Ya Chen, Li-Ru Bai, Yan Zhou, Jin-Lan Huang, Zhen-Guo Zhong
Most of the existing chemotherapeutic drugs have plenty of side effects. Chinese herbal medicine has been used for pharmaceutical and dietary therapy for thousands of years with more effective and fewer side effects. Cestrum nocturnum (CN) has long been used to treat digestive diseases for centuries in China. Our previous study first proved that the n-butanol part isolated from the flowers of CN produced an inhibitory effect on the proliferation of malignant cells. However, the fractions responsible for the antiproliferation effect of n-butanol part from CN flowers and related mechanisms remain unknown...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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