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[PMID]: 28453010 [Au] Autor: Sethi S; Ooe M; Sakamoto T; Fujimoto K [Ad] Endereço: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan. kenzo@jaist.ac.jp. [Ti] Título: Effect of nucleobase change on cytosine deamination through DNA photo-cross-linking reaction via 3-cyanovinylcarbazole nucleoside. [So] Source: Mol Biosyst;13(6):1152-1156, 2017 Jun 01. [Is] ISSN: 1742-2051 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Photo-chemical deamination of cytosine using 3-cyanovinylcarbazole nucleoside ( K) mediated photo-cross-linking is a technique for site-directed mutagenesis. Using this technique in vivo requires the elimination of a high-temperature incubation step; instead, incubation should be carried out under physiological conditions. To improve the reactivity of K mediated photo-cross-link induced deamination of cytosine under physiological conditions, an evaluation of base pairing in cytosine was carried out with respect to its deamination. Guanine was replaced with 4 different counter bases (inosine, 2-aminopurine, 5-nitroindole, and nebularine), showing distinct hydrogen bonding patterns with target cytosine, which was incorporated at the -1 position with respect to K in the K-modified photo-responsive oligodeoxyribonucleotides to ascertain the role of hydrogen bonding in deamination under physiological conditions. Among the counter bases, inosine showed the highest acceleration towards the photo-induced deamination reaction. [Mh] Termos MeSH primário: Citosina/química DNA/química Guanina/química Nucleosídeos/química [Mh] Termos MeSH secundário: 2-Aminopurina/química Pareamento de Bases Desaminação Ligações de Hidrogênio Indóis/química Estrutura Molecular Mutagênese Sítio-Dirigida Oligodesoxirribonucleotídeos/química Nucleosídeos de Purina/química Ribonucleosídeos/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Indoles); 0 (Nucleosides); 0 (Oligodeoxyribonucleotides); 0 (Purine Nucleosides); 0 (Ribonucleosides); 452-06-2 (2-Aminopurine); 5Z93L87A1R (Guanine); 8J337D1HZY (Cytosine); 9007-49-2 (DNA); B8B604PS4P (nebularine); O2BHX6EDBN (5-nitroindole) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE [do] DOI: 10.1039/c7mb00082k

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[PMID]: 29179216 [Au] Autor: Sakai G; Tokuda H; Fujita K; Kainuma S; Kawabata T; Matsushima-Nishiwaki R; Kozawa O; Otsuka T [Ad] Endereço: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. [Ti] Título: Heat Shock Protein 70 Negatively Regulates TGF-ß-Stimulated VEGF Synthesis via p38 MAP Kinase in Osteoblasts. [So] Source: Cell Physiol Biochem;44(3):1133-1145, 2017. [Is] ISSN: 1421-9778 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: BACKGROUND/AIMS: We previously demonstrated that transforming growth factor-ß (TGF-ß) stimulates the synthesis of vascular endothelial growth factor (VEGF) through the activation of p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. Heat shock protein70 (HSP70) is a ubiquitously expressed molecular chaperone. In the present study, we investigated the involvement of HSP70 in the TGF-ß-stimulated VEGF synthesis and the underlying mechanism in these cells. METHODS: Culture MC3T3-E1 cells were stimulated by TGF-ß. Released VEGF was measured using an ELISA assay. VEGF mRNA level was quantified by RT-PCR. Phosphorylation of each protein kinase was analyzed by Western blotting. RESULTS: VER-155008 and YM-08, both of HSP70 inhibitors, significantly amplified the TGF-ß-stimulated VEGF release. In addition, the expression level of VEGF mRNA induced by TGF-ß was enhanced by VER-155008. These inhibitors markedly strengthened the TGF-ß-induced phosphorylation of p38 MAP kinase. The TGF-ß-induced phosphorylation of p38 MAP kinase was amplified in HSP70-knockdown cells. SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by these inhibitors of the TGF-ß-induced VEGF release. CONCLUSION: These results strongly suggest that HSP70 acts as a negative regulator in the TGF-ß-stimulated VEGF synthesis in osteoblasts, and that the inhibitory effect of HSP70 is exerted at a point upstream of p38 MAP kinase. [Mh] Termos MeSH primário: Proteínas de Choque Térmico HSP70/metabolismo Fator de Crescimento Transformador beta/farmacologia Fator A de Crescimento do Endotélio Vascular/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo [Mh] Termos MeSH secundário: Animais Benzotiazóis/farmacologia Linhagem Celular Ensaio de Imunoadsorção Enzimática Proteínas de Choque Térmico HSP70/antagonistas & inibidores Proteínas de Choque Térmico HSP70/genética Imidazóis/farmacologia Camundongos Osteoblastos/citologia Osteoblastos/efeitos dos fármacos Osteoblastos/metabolismo Fosforilação/efeitos dos fármacos Nucleosídeos de Purina/farmacologia Piridinas/farmacologia Interferência de RNA RNA Interferente Pequeno Reação em Cadeia da Polimerase em Tempo Real Proteína Smad2/metabolismo Proteína Smad3/metabolismo Tiazolidinas/farmacologia Fator A de Crescimento do Endotélio Vascular/análise Fator A de Crescimento do Endotélio Vascular/genética Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Benzothiazoles); 0 (HSP70 Heat-Shock Proteins); 0 (Imidazoles); 0 (Purine Nucleosides); 0 (Pyridines); 0 (RNA, Small Interfering); 0 (Smad2 Protein); 0 (Smad3 Protein); 0 (Thiazolidines); 0 (Transforming Growth Factor beta); 0 (VER 155008); 0 (Vascular Endothelial Growth Factor A); 0 (YM-08 compound); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); OU13V1EYWQ (SB 203580) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180118 [Lr] Data última revisão: 180118 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171128 [St] Status: MEDLINE [do] DOI: 10.1159/000485418

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[PMID]: 29185853 [Au] Autor: Ananda Mohan A; Veera Raghava Sharma G; Vidavalur S [Ad] Endereço: a Department of Organic Chemistry , Dr. B.R. Ambedkar University , Srikakulam, Etcherla , Andhra Pradesh , India. [Ti] Título: Synthesis, characterization and biological evaluation of C5'-N-cyclopropylcarboxamido-C6-amino-C2-alkynylated purine nucleoside analogues. [So] Source: Nucleosides Nucleotides Nucleic Acids;36(10):637-651, 2017 Oct 03. [Is] ISSN: 1532-2335 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: In an effort to develop potent antibacterial and anticancer agents, a series of C5'-N-cyclopropylcarboxamido-C6-amino-C2-alkynylated purine nucleoside analogues 11a-g were synthesized through a Sonogashira cross-coupling reaction. The nine-step synthesis is easy to perform, and employs commercially available reagents. 2-Iodo-5'-N-cyclopropylcarboxamidoadenosine (9) was used as the starting intermediate for the synthesis of title derivatives 11a-g. Synthetic intermediates (2-9) and final products (11a-g) were appropriately characterized by IR, H NMR, C NMR and mass spectroscopy. The synthesized purine nucleoside analogues (11a-g) were evaluated for their in vitro antibacterial activity against two gram-positive and two gram-negative bacteria. They were then tested for cytotoxicity against MDA-MB-231 and Caco-2 cancer cell lines to determine their anti-cancer activity. Among the tested compounds, compounds 11c and 11g showed most potent antibacterial activity against S.aureus and P.aeruginosa bacterial strains. Compounds 11b and 11e displayed considerable IC of 7.9 and 6.8 µg/mL, respectively, vs MDA-MB-231 cell lines of 7.5 and 8.3 µg/mL, respectively, against the Caco-2 cell lines. [Mh] Termos MeSH primário: Alquinos/química Antibacterianos/síntese química Antibacterianos/farmacologia Antineoplásicos/síntese química Antineoplásicos/farmacologia Nucleosídeos de Purina/síntese química Nucleosídeos de Purina/farmacologia [Mh] Termos MeSH secundário: Amidas/química Antibacterianos/química Antineoplásicos/química Linhagem Celular Tumoral Técnicas de Química Sintética Seres Humanos Nucleosídeos de Purina/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Alkynes); 0 (Amides); 0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents); 0 (Purine Nucleosides) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180105 [Lr] Data última revisão: 180105 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171130 [St] Status: MEDLINE [do] DOI: 10.1080/15257770.2017.1375117

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[PMID]: 29087802 [Au] Autor: Halay E; Ay E; Salva E; Ay K; Karayildirim T [Ad] Endereço: a Scientific Analysis Technological Application and Research Center , Usak University , Usak , Turkey. [Ti] Título: Syntheses of 1,2,3-triazole-bridged pyranose sugars with purine and pyrimidine nucleobases and evaluation of their anticancer potential. [So] Source: Nucleosides Nucleotides Nucleic Acids;36(9):598-619, 2017 Sep 02. [Is] ISSN: 1532-2335 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: With the aim to create a library of compounds with potential bioactivities by combining special characteristics of two important groups such as nucleobases and carbohydrates, twenty 1,4-disubstituted-triazole nucleosides were synthesized in good yields (80-94%) using the copper catalyzed 'Click' reaction between azido-modified pento- or hexopyranoses and alkyne-bearing pyrimidine or purine nucleobases. Structural elucidation was made with the assistance of spectroscopic techniques such as FTIR, 1D-, 2D-NMR, and ESI-TOFMS. All the synthesized triazole nucleosides were evaluated for their cytotoxic activity against three human cancer cell lines (MDA-MB-231, Hep3B, PC-3) by using the MTT assay. Particularly, compounds 3a and 1b were identified as potential hits against Hep3B cell. [Mh] Termos MeSH primário: Antineoplásicos/síntese química Antineoplásicos/farmacologia Nucleosídeos de Purina/química Piranos/química Nucleosídeos de Pirimidina/química Triazóis/síntese química Triazóis/farmacologia [Mh] Termos MeSH secundário: Antineoplásicos/química Linhagem Celular Tumoral Técnicas de Química Sintética Seres Humanos Triazóis/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Purine Nucleosides); 0 (Pyrans); 0 (Pyrimidine Nucleosides); 0 (Triazoles) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171113 [Lr] Data última revisão: 171113 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171101 [St] Status: MEDLINE [do] DOI: 10.1080/15257770.2017.1346258

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[PMID]: 28691182 [Au] Autor: Kita K; Shiota M; Tanaka M; Otsuka A; Matsumoto M; Kato M; Tamada S; Iwao H; Miura K; Nakatani T; Tomita S [Ad] Endereço: Department of Urology, Osaka City University Medical School, Osaka, Japan. [Ti] Título: Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells. [So] Source: Cancer Sci;108(9):1820-1827, 2017 Sep. [Is] ISSN: 1349-7006 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Androgen deprivation therapy is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7. In this study, we investigated the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer cell line LNCaP95 that expresses AR-V7, and explored the mechanism by which Hsp70 regulates AR-FL and AR-V7 expression. Quercetin and VER155008 decreased cell proliferation, increased the proportion of apoptotic cells, and decreased the protein levels of AR-FL and AR-V7. Furthermore, VER155008 decreased AR-FL and AR-V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry identified Y-box binding protein 1 (YB-1) as one of the molecules regulating AR-FL and AR-V7 at the transcription level through interaction with Hsp70. VER155008 decreased the phosphorylation of YB-1 and its localization in the nucleus, indicating that the involvement of Hsp70 in AR regulation might be mediated through the activation and nuclear translocation of YB-1. Collectively, these results suggest that Hsp70 inhibitors have potential anti-tumor activity against CRPC by decreasing AR-FL and AR-V7 expression through YB-1 suppression. [Mh] Termos MeSH primário: Antineoplásicos Hormonais/farmacologia Expressão Gênica/efeitos dos fármacos Neoplasias da Próstata/tratamento farmacológico Nucleosídeos de Purina/farmacologia Receptores Androgênicos/genética [Mh] Termos MeSH secundário: Linhagem Celular Tumoral Proliferação Celular/efeitos dos fármacos Sobrevivência Celular/efeitos dos fármacos Inativação Gênica/efeitos dos fármacos Proteínas de Choque Térmico HSP70/antagonistas & inibidores Proteínas de Choque Térmico HSP70/metabolismo Seres Humanos Masculino Neoplasias da Próstata/metabolismo Quercetina/farmacologia Receptores Androgênicos/metabolismo Proteína 1 de Ligação a Y-Box/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents, Hormonal); 0 (HSP70 Heat-Shock Proteins); 0 (Purine Nucleosides); 0 (Receptors, Androgen); 0 (VER 155008); 0 (Y-Box-Binding Protein 1); 0 (YBX1 protein, human); 9IKM0I5T1E (Quercetin) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170711 [St] Status: MEDLINE [do] DOI: 10.1111/cas.13318

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[PMID]: 28504647 [Au] Autor: Nayar U; Sadek J; Reichel J; Hernandez-Hopkins D; Akar G; Barelli PJ; Sahai MA; Zhou H; Totonchy J; Jayabalan D; Niesvizky R; Guasparri I; Hassane D; Liu Y; Sei S; Shoemaker RH; Warren JD; Elemento O; Kaye KM; Cesarman E [Ad] Endereço: Department of Pathology and Laboratory Medicine. [Ti] Título: Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies. [So] Source: J Clin Invest;127(6):2066-2080, 2017 Jun 01. [Is] ISSN: 1558-8238 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers. [Mh] Termos MeSH primário: Adenosina Quinase/metabolismo Antineoplásicos/farmacologia Linfoma de Efusão Primária/tratamento farmacológico Nucleosídeos de Purina/farmacologia [Mh] Termos MeSH secundário: Animais Linhagem Celular Tumoral Sobrevivência Celular/efeitos dos fármacos Resistência a Medicamentos Antineoplásicos Seres Humanos Concentração Inibidora 50 Linfoma de Efusão Primária/enzimologia Masculino Camundongos Camundongos Endogâmicos NOD Camundongos SCID Ensaios Antitumorais Modelo de Xenoenxerto [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (NSC39368); 0 (Purine Nucleosides); EC 2.7.1.20 (Adenosine Kinase) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170926 [Lr] Data última revisão: 170926 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170516 [St] Status: MEDLINE

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[PMID]: 28447489 [Au] Autor: Lewis DJ; Duvic M [Ad] Endereço: a School of Medicine , Baylor College of Medicine , Houston , TX , USA. [Ti] Título: Forodesine in the treatment of cutaneous T-cell lymphoma. [So] Source: Expert Opin Investig Drugs;26(6):771-775, 2017 Jun. [Is] ISSN: 1744-7658 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is characterized by the accumulation of neoplastic CD4+ T lymphocytes in the skin. Given the lack of curative treatments for CTCL, there is a significant need for new, superior therapies. Forodesine is a transition-state analogue that inhibits purine nucleoside phosphorylase. Because it selectively targets T lymphocytes, it represents a drug of interest for the treatment of CTCL. Areas covered: Phase I/II dose-ranging studies of intravenous (IV) and oral forodesine demonstrated its activity, safety, and tolerability for refractory CTCL. Response rates were 31% and 27%, respectively. No dose-limiting toxicities were observed. These studies were followed by a phase II trial of oral forodesine 200 mg daily. This oral formulation showed only partial activity, with a response rate of 11%, likely attributable to underdosing. Common adverse events in these trials included infection, fatigue, peripheral edema, nausea, pruritus, headache, and insomnia. Expert opinion: IV and oral formulations of forodesine have demonstrated partial activity and an acceptable safety profile in patients with refractory CTCL. A higher oral dose, or sequential therapy consisting of IV forodesine followed by maintenance oral forodesine, may be more effective. With proper dosing, forodesine may emerge as a safe and effective treatment for refractory CTCL. [Mh] Termos MeSH primário: Linfoma Cutâneo de Células T/tratamento farmacológico Nucleosídeos de Purina/administração & dosagem Pirimidinonas/administração & dosagem Neoplasias Cutâneas/tratamento farmacológico [Mh] Termos MeSH secundário: Administração Intravenosa Administração Oral Animais Antineoplásicos/administração & dosagem Antineoplásicos/efeitos adversos Antineoplásicos/farmacologia Relação Dose-Resposta a Droga Seres Humanos Linfoma Cutâneo de Células T/patologia Nucleosídeos de Purina/efeitos adversos Nucleosídeos de Purina/farmacologia Pirimidinonas/efeitos adversos Pirimidinonas/farmacologia Neoplasias Cutâneas/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antineoplastic Agents); 0 (Purine Nucleosides); 0 (Pyrimidinones); 426X066ELK (forodesine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170621 [Lr] Data última revisão: 170621 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170428 [St] Status: MEDLINE [do] DOI: 10.1080/13543784.2017.1324569

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[PMID]: 28252180 [Au] Autor: Maity J; Srivastava S; Sanghvi YS; Prasad AK; Stromberg R [Ad] Endereço: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Sweden. [Ti] Título: Facile Access to Bromonucleosides Using Sodium Monobromoisocyanurate (SMBI). [So] Source: Curr Protoc Nucleic Acid Chem;68:1.39.1-1.39.9, 2017 Mar 02. [Is] ISSN: 1934-9289 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Bromonucleosides constitute a significant class of molecules and are well known for their biological activity. 5-Bromouridine, 5-bromo-2'-deoxyuridine, 5-bromouridine-5'-triphosphate, and nucleotides containing 5-bromouridine have been tested and used for numerous biological studies. 8-Bromopurine nucleosides have been used as essential precursors for the synthesis of nucleosides with fluorescent properties. This unit describes protocols for the synthesis of bromonucleosides using sodium monobromoisocyanurate (SMBI) in a straightforward way. Reactions are carried out at room temperature, and aqueous solvent mixtures are used to dissolve the nucleosides. Sodium azide is used as catalyst for the bromination of pyrimidine nucleosides, and no catalyst is necessary for the bromination of purine nucleosides. Unprotected 2'-deoxy pyrimidine and 2'-deoxy purine nucleosides are treated with SMBI to afford C-5 bromo pyrimidine and C-8 bromo purine nucleosides, respectively. This methodology has been found to be efficient for the synthesis of bromonucleosides on gram scale with consistently high yields. © 2017 by John Wiley & Sons, Inc. [Mh] Termos MeSH primário: Nucleosídeos de Purina/síntese química Nucleosídeos de Pirimidina/síntese química [Mh] Termos MeSH secundário: Bromodesoxicitidina/síntese química Bromodesoxicitidina/química Bromodesoxiuridina/síntese química Técnicas de Química Sintética Desoxiadenosinas/síntese química Desoxiadenosinas/química Desoxiguanosina/análogos & derivados Desoxiguanosina/síntese química Desoxiguanosina/química Nucleosídeos de Purina/química Nucleosídeos de Pirimidina/química Uridina/análogos & derivados Uridina/síntese química Uridina/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (8-bromo-2'-deoxyguanosine); 0 (Deoxyadenosines); 0 (Purine Nucleosides); 0 (Pyrimidine Nucleosides); 1022-79-3 (Bromodeoxycytidine); 14985-44-5 (8-bromo-2'-deoxyadenosine); G34N38R2N1 (Bromodeoxyuridine); G9481N71RO (Deoxyguanosine); KEY8PG1BRC (5-bromouridine); WHI7HQ7H85 (Uridine) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170515 [Lr] Data última revisão: 170515 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170303 [St] Status: MEDLINE [do] DOI: 10.1002/cpnc.24

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[PMID]: 28237998 [Au] Autor: Ha S; Lee KJ; Lee SI; Gwak HJ; Lee JH; Kim TW; Choi HJ; Jang JY; Choi JS; Kim CJ; Kim JC; Kim HH; Park HW [Ad] Endereço: World Institute of Kimchi, Gwangju 61755, Republic of Korea. [Ti] Título: Optimization of Herbicidin A Production in Submerged Culture of M40. [So] Source: J Microbiol Biotechnol;27(5):947-955, 2017 May 28. [Is] ISSN: 1738-8872 [Cp] País de publicação: Korea (South) [La] Idioma: eng [Ab] Resumo: Herbicidin A is a potent herbicide against dicotyledonous plants as well as an antibiotic against phytopathogens. In this study, fermentation parameters for herbicidin A production in submerged culture of M40 were investigated. The herbicidin A concentration varied with the C/N ratio. High C/N ratios (>4) resulted in a herbicidin A production of more than 900 mg/l, whereas maximally 600 mg/l was obtained at ratios between 1 and 3.5. In 5-L batch fermentation, there was a positive correlation between the oxygen uptake rate (OUR) and herbicidin A production. Once the OUR increased, the substrate consumption rate increased, leading to an increase in volumetric productivity. Mechanical shear force affected the hyphal morphology and OUR. When the medium value of hyphal size ranged from 150 to 180 µm, high volumetric production of herbicidin A was obtained with OUR values >137 mg O /l·h. The highest herbicidin A concentration of 956.6 mg/l was obtained at 500 rpm, and coincided with the highest relative abundance of hyphae of 100-200 µm length and the highest OUR during cultivation. Based on a constant impeller tip speed, which affects hyphal morphology, herbicidin A production was successfully scaled up from a 5-L jar to a 500-L pilot vessel. [Mh] Termos MeSH primário: Técnicas de Cultura de Células/métodos Meios de Cultura/química Fermentação Nucleosídeos de Purina/biossíntese Streptomyces/metabolismo [Mh] Termos MeSH secundário: Técnicas Bacteriológicas Técnicas de Cultura Celular por Lotes/métodos Reatores Biológicos Carbono/metabolismo Glucose/metabolismo Hifas/citologia Hifas/crescimento & desenvolvimento Hifas/metabolismo Nitrogênio/metabolismo Oxigênio Projetos Piloto Rotação Feijão de Soja/química Streptomyces/citologia Streptomyces/crescimento & desenvolvimento Temperatura Ambiente Fatores de Tempo Zea mays/química [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Culture Media); 0 (Purine Nucleosides); 7440-44-0 (Carbon); 77699-46-8 (herbicidins); IY9XDZ35W2 (Glucose); N762921K75 (Nitrogen); S88TT14065 (Oxygen) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171031 [Lr] Data última revisão: 171031 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170227 [St] Status: MEDLINE [do] DOI: 10.4014/jmb.1611.11005

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[PMID]: 28188891 [Au] Autor: Bonassi S; Cellai F; Munnia A; Ugolini D; Cristaudo A; Neri M; Milic M; Bonotti A; Giese RW; Peluso ME [Ad] Endereço: Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy; Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy. [Ti] Título: 3-(2-deoxy-ß-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers. [So] Source: Toxicol Lett;270:1-7, 2017 Mar 15. [Is] ISSN: 1879-3169 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-ß-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M dG per 10 normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where M dG may reflect an additional potential mechanism of asbestos-induced toxicity. [Mh] Termos MeSH primário: Asbestos/toxicidade Adutos de DNA/sangue Desoxiguanosina/toxicidade Exposição Ocupacional/efeitos adversos Nucleosídeos de Purina/toxicidade [Mh] Termos MeSH secundário: Idoso Asbestos/sangue Biomarcadores/sangue Estudos Transversais Desoxiguanosina/sangue Escolaridade Seres Humanos Itália Peroxidação de Lipídeos/efeitos dos fármacos Masculino Meia-Idade Estresse Oxidativo/efeitos dos fármacos Nucleosídeos de Purina/sangue Espécies Reativas de Oxigênio/metabolismo Fumar [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido(1,2-alpha)purin-10(3H)-one); 0 (Biomarkers); 0 (DNA Adducts); 0 (Purine Nucleosides); 0 (Reactive Oxygen Species); 1332-21-4 (Asbestos); G9481N71RO (Deoxyguanosine) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170320 [Lr] Data última revisão: 170320 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170212 [St] Status: MEDLINE

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