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Sample records for aulacomya atra atra

  1. Effects of varied interferons in combination with all-trans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell

    Institute of Scientific and Technical Information of China (English)

    HE Peng-cheng; ZHANG Mei; LI Jing; CAI Rui-bo; LIU Ya-lin; CAO Yun-xin

    2006-01-01

    Objective:To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell. Methods :After MR2 cells (ATRA-resistance cell line) were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell roliferation was tested by MTT test and the cell differentiation was tested through light microscope by NBT test and flow cytometry (FCM). The expression of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent method. Results: Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively (P<0. 05). Moreover, the maturation of MR2 cells induced by IFN-γ+ATRA group was more higher than that by IFN-α+ATRA group (P<0.05). Both interferons could induce the expressions of PML protein. Conclusion :Both interferons can inhibit MR2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ+ATRA group on MR2 cells are more powerful than those of IFN-α+ATRA group, which may be related to the different signal transduction pathway of both interferons.

  2. Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

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    Gelcimar Moresco

    2011-06-01

    Full Text Available O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA, que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA. Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

  3. Protaeolidiella atra Baba, 1955 versus Pleurolidia juliae Burn, 1966: One or two species?

    Science.gov (United States)

    Carmona, Leila; Pola, Marta; Gosliner, Terrence M.; Cervera, Juan Lucas

    2015-06-01

    Protaeolidiella atra Baba, 1955 and Pleurolidia juliae Burn, 1966 are two species traditionally regarded as the members of Aeolidiidae but recently attributed to Facelinidae. Because of their apparent similarities, Rudman (J Molluscan Stud 56:505-514, 1990) rendered P. juliae as a junior synonym of P. atra. In this paper, we conducted a review of both species and completed their descriptions with new data regarding the anatomy of the reproductive system . P. atra and P. juliae have differences in their colouration, number of cerata and characteristics of their reproductive system. Based on these differences, we conclude that these species are not conspecific and should be regarded as distinct taxa.

  4. ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.

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    Clarke, Christopher J; Shamseddine, Achraf A; Jacob, Joseph J; Khalife, Gabrielle; Burns, Tara A; Hannun, Yusuf A

    2016-05-01

    Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels. PMID:27013100

  5. Territory and territorial behavior of migrating Common Coot (Fulica atra)

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-wei; LIU Wei; MA Jian-zhang

    2011-01-01

    Territory and territorial behavior of the Common Coot (Fulica atra) were studied in two breeding sites, Anbanghe Nature Reserve and Daqing Longfeng wetland, in Heilongjiang Province, China from April to October in 2008 and 2009.In the breeding season, the breeding pairs occupied an area and protected it throughout the reproduction, and both interspecific and intraspecific conflicts were observed.Territory activities became severe since early May, the peak of territory behaviors appeared at late May, and then declined gradually.The territorial activities level was higher than that in the nest building period than in the laying and incubation periods.The most adopted behavioral model was expelling,which was the least energy cost.The degree of territorial behavior tended to be descended since the development of breeding phase.The territory size differed from 1 333 m2 to above 5 000 m2.Wintering population was observed in Poyang Lake of Jiangxi Province.The coots gathered in the open water; however, there was no territory behavior both in the interspecies and intraspecies in wintering sites.The hypotheses why there was territory behaviors for coots both in the interspecies and intraspecies were also discussed.

  6. Toxicity effects of water extracts of Holothuria atra Jaeger in mice

    Institute of Scientific and Technical Information of China (English)

    Ridzwan Bin Hashim; Nurul Alia Azizan; Zaitunnatakin Zamli; Farah Hanis Zulkipli; Nurzafirah Mazlan; Osama Yousef Althunibat

    2014-01-01

    Objective:To determine lethal median dose (LD50) and histopathological toxicity of water extract of Holothuria atra (H. atra) in mice. Methods: The behavioral changes, mortality and histopathology examination on liver were assessed in mice 14 d after the administration (i.p.) of H. atra water extract. Seven doses (10, 20, 30, 50, 100, 150 and 200 mg/kg) of H. atra were used. The control group was treated with normal saline. Results:In the acute study in mice, the water extracts of H. atra caused dose-dependent general behavior adverse affects and mortality. The main behavioral sign of toxicity was hypoactivity, noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death. Mortality increased with increasing doses, the calculated LD50 was 41 mg/kg in mice. The liver toxicity was confirmed by histopathological examination, which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups. High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining, massive cytoplasm, pyknotic, karyorhexis and karyolytic nuclei (necrosis of hepatocytes). Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei, with granular cytoplasm. Conclusions: Because of the relatively low LD50 value in the acute study in mice, it may be concluded that the H. atra water extract is toxic.

  7. Activation of RARα induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity.

    Science.gov (United States)

    Brigger, D; Schläfli, A M; Garattini, E; Tschan, M P

    2015-01-01

    All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is, along with other retinoids, a promising therapeutic agent for the treatment of a variety of solid tumors. On the one hand, preclinical studies have shown promising anticancer effects of ATRA in breast cancer; on the other hand, resistances occurred. Autophagy is a cellular recycling process that allows the degradation of bulk cellular contents. Tumor cells may take advantage of autophagy to cope with stress caused by anticancer drugs. We therefore wondered if autophagy is activated by ATRA in mammary tumor cells and if modulation of autophagy might be a potential novel treatment strategy. Indeed, ATRA induces autophagic flux in ATRA-sensitive but not in ATRA-resistant human breast cancer cells. Moreover, using different RAR agonists as well as RARα-knockdown breast cancer cells, we demonstrate that autophagy is dependent on RARα activation. Interestingly, inhibition of autophagy in breast cancer cells by either genetic or pharmacological approaches resulted in significantly increased apoptosis under ATRA treatment and attenuated epithelial differentiation. In summary, our findings demonstrate that ATRA-induced autophagy is mediated by RARα in breast cancer cells. Furthermore, inhibition of autophagy results in enhanced apoptosis. This points to a potential novel treatment strategy for a selected group of breast cancer patients where ATRA and autophagy inhibitors are applied simultaneously. PMID:26313912

  8. Receptor-mediated delivery of all-trans-retinoic acid (ATRA) to hepatocytes from ATRA-loaded poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) nanoparticles

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    Seo, Seog-Jin [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Moon, Hyun-Seuk [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Guo, Ding-Ding [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Kim, Sang-Heon [Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of) ; Akaike, Toshihiro [Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501 (Japan); Cho, Chong-Su [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ]. E-mail: chocs@plaza.snu.ac.kr

    2006-01-15

    All-trans-retinoic acid (ATRA) plays a role in regulating CYP26 gene expression in hepatocytes. Poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) (PVLA) nanoparticles have been used as hepatocyte-specific targeting candidates. The objective of this study was to investigate receptor-mediated delivery of ATRA using PVLA nanoparticles. ATRA-loaded PVLA nanoparticles were confirmed by {sup 1}H-nuclear magnetic resonance ({sup 1}H-NMR) and powder X-ray diffraction (XRD). In the {sup 1}H-NMR study, the proton signals of ATRA disappeared in the spectrum of ATRA-loaded PVLA nanoparticles in D{sub 2}O, whereas in dimethylsulfoxide-d{sub 6}, the spectrum seemed like an addition of the respective spectrum of each of the pure components. The crystalline peaks of ATRA disappeared in the XRD pattern of ATRA-loaded PVLA nanoparticles after ATRA was loaded into PVLA nanoparticles. In the measurement of size distribution, diameter of PVLA and ATRA-loaded PVLA nanoparticles in aqueous solution was 6.9 and 61.2 nm in number average, respectively. Flow cytometric analysis showed that the internalization of FITC-PVLA nanoparticles by hepatocytes in the absence of a competitive inhibitor was larger than preincubated with galactose. In reverse transcription-polymerase chain reaction (RT-PCR) analysis, ATRA-loaded PVLA nanoparticles induced CYP26A1 gene in hepatocytes in the absence of a competitive inhibitor but not preincubated with galactose. The results indicate that the ATRA-loaded PVLA nanoparticle can induce CYP26A1 gene in aqueous phase by an asialoglycoprotein receptor (ASGPR)-mediated delivery system.

  9. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

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    Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

    2014-10-10

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  10. Discovery of Salamandra atra aurorae (Trevisan, 1982 on the Altopiano di Vezzena, Trentino (Northeastern Italy

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    Wouter Beukema

    2008-05-01

    Full Text Available Aurora’s Alpine Salamander is a limited distributed subspecies endemic to the Altopiano di Asiago, Veneto. In the current paper the occurrence of Salamandra atra aurorae is described for the Altopiano di Vezzena, Trentino. The aim of this paper is to review the distribution as well as to comment on the conservational status of the subspecies in Trentino.

  11. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation.

    Science.gov (United States)

    Akter, Jesmin; Takatori, Atsushi; Islam, Md Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

    2014-10-10

    We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  12. LG-362B targets PML-RARα and blocks ATRA resistance of acute promyelocytic leukemia.

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    Wang, X; Lin, Q; Lv, F; Liu, N; Xu, Y; Liu, M; Chen, Y; Yi, Z

    2016-07-01

    Acute promyelocytic leukemia (APL) is a M3 subtype of acute myeloid leukemia (AML). Promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) translocation generally occurs in APL patients and makes APL unique both for diagnosis and treatment. However, some conventional drugs like all-transretinoic acid (ATRA) and arsenic trioxide (ATO), as the preferred ones for APL therapy, induce irreversible resistance and responsible for clinical failure of complete remission. Herein, we screened a library of novel chemical compounds with structural diversity and discovered a novel synthetic small compound, named LG-362B, specifically inhibited the proliferation of APL and induced apoptosis. Notably, the differentiation arrest was also relieved by LG-362B in cultured APL cells and APL mouse models. Moreover, LG-362B overcame the ATRA resistance on cellular differentiation and transplantable APL mice. These positive effects were driven by caspases-mediated degradation of PML-RARα when treated with LG-362B, making it specific to APL and reasonable for ATRA resistance relief. We propose that LG-362B would be a potential candidate agent for the treatment of the relapsed APL with ATRA resistance in the future.

  13. Atrações e prazeres visuais em um pornô feminino

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    Mariana Baltar

    2015-01-01

    Este artigo correlaciona os conceitos de excesso e atrações como estratégicos para refletir sobre processos de engajamento e afetação no campo da pornografia que desestabilizam morais tradicionais em direção a uma política de gêneros. Nesse sentido, mobiliza-se uma lógica de excesso de atrações que estabelece um jogo ambivalente de recusa e adesão aos códigos genéricos mais básicos da pornografia. Os argumentos são empreendidos a partir da análise de Dirty Diaries, um projeto declaradamente a...

  14. Atrações e prazeres visuais em um pornô feminino

    Directory of Open Access Journals (Sweden)

    Mariana Baltar

    2015-08-01

    Full Text Available Este artigo correlaciona os conceitos de excesso e atrações como estratégicos para refletir sobre processos de engajamento e afetação no campo da pornografia que desestabilizam morais tradicionais em direção a uma política de gêneros. Nesse sentido, mobiliza-se uma lógica de excesso de atrações que estabelece um jogo ambivalente de recusa e adesão aos códigos genéricos mais básicos da pornografia. Os argumentos são empreendidos a partir da análise de Dirty Diaries, um projeto declaradamente associado ao campo da pornografia feminista empreendido com apoio do Swedish Film Institut.

  15. Neutron dosimetry and damage calculations for the ATR-A1 irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Neutron fluence measurements and radiation damage calculations are reported for the collaborative US/Japan ATR-A1 irradiation in the Advanced Test Reactor (ATR) at Idaho National Engineering Laboratory (INEL). The maximum total neutron fluence at midplane was 9.4 {times} 10{sup 21} n/cm{sup 2} (5.5 {times} 10{sup 21} n/cm{sup 2} above 0.1 MeV), resulting in about 4.6 dpa in vanadium.

  16. Toxicity effects of water extracts of Holothuria atra Jaeger in mice

    Institute of Scientific and Technical Information of China (English)

    Ridzwan; Bin; Hashim; Nurul; Alia; Azizan; Zaitunnatakin; Zamli; Farah; Hanis; Zulkipli; Nurzafirah; Mazlan; Osama; Yousef; Althunibat

    2014-01-01

    Objective:To determine lethal median dose(LD50) and histopalhological toxicity of water extract of Hololhuria atra(H,atra) in mice.Methods:The behavioral changes,mortality and histopathology examination on liver were assessed in mice 14 d after the administration(i.p.) of H.atra water extract.Seven doses 110,20,30,50.100.150 and 200 mg/kg) of H.atra were used.The control group was treated with normal saline,Results:In the acute study in mice,the water extracts of H,atra caused dose-dependent general behavior adverse affects and mortality.The main behavioral sign of toxicity was hypoactivity,noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death.Mortality increased with increasing doses,the calculated LD50was 41 mg/kg in mice.The liver toxicity was confirmed by histopalhological examination,which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups.High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining,massive cytoplasm,pvknotic.karyorhexis and karyolytie nuclei(necrosis of hepatocytes).Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei,with granular cytoplasm.Conclusions:Because of the relatively low LD50 value in the acute study in mice,it may be concluded that the H.atra water extract is toxic.

  17. Gateways to Hawai‘i: Genetic Population Structure of the Tropical Sea Cucumber Holothuria atra

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    Derek J. Skillings

    2011-01-01

    Full Text Available Holothuria atra is one of the most common and widest ranging tropical, coral reef sea cucumbers in the world, and here we examine population genetic structure based on mitochondrial COI to aid in determining the appropriate scale for coral reef management. Based on SAMOVA, AMOVA and BARRIER analyses, we show that despite its large range, H. atra has hierarchical, fine-scale population structure driven primarily by between-archipelago barriers, but with significant differences between sites within an archipelago as well. Migrate analyses along with haplotype networks and patterns of haplotype diversity suggest that Hawai‘i and Kingman reef are important centers of the genetic diversity in the region rather than an evolutionary dead-end for migrants from the Indo-Pacific. Finally we show that for H. atra Kingman Reef is the most likely stepping stone between Hawai‘i and the rest of the Pacific, not Japan or Johnston Atoll as previously presumed. Based on our data, Johnston Atoll can instead be seen as an outpost of the Northwestern Hawaiian Islands rather than a gateway to the Hawaiian Archipelago.

  18. EFFECT OF ARSENIC TRIOXIDE OR ATRA ON PRIMARY APL CELL OR HL-60 CELLS AND THEIR VALUE ANALYSIS IN HYPERLEUKOCYTOSIS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To detect the effect of arsenic trioxide or ATRA on APL cells or HL-60 cells and to investigate the mechanism of the hyperleukocytosis and detect the cross resistance between ATRA and arsenic trioxide. Methods: The number of promyelocytes or more matured granulocytes were counted by regular method, MTT test was used to measure the proliferation of HL-60 cells or APL cells, flow cytometry analysis to measure the apoptosis, NBT method to detect the differentiation of HL-60 cells or APL cells. Results: The proliferation of primary APL cells or HL-60 cells could be inhibited in vitro by either arsenic trioxide or ATRA, which could induce obvious apoptosis or obvious differentiation of primary APL cells or HL-60 cells. Inhibition of proliferation or apoptosis of ATRA resistant HL-60 cells were achieved by exposure toarsenic trioxide in vitro. On the other hand, the results of in vivo treatment showed that arsenic trioxide also induce of hyperleukocytosis. Conclusion: The results indicated that the hyperleukocytosis induced by ATRA is not contributed to the mechanism of more differentiation than apoptosis, there was not cross resistance between ATRA and arsenic trioxide.

  19. Effect of ATRA on Contents of liver Retinoids, Oxidative Stress and Hepatic Injury in Rat Model of Extrahepatic Cholestasis

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    JIANG Haiyan; DAN Zili; WANG Hui; LIN Jusheng

    2007-01-01

    The effects of all-trans-retinoic acid (ATRA) administration on the concentration of retinoids (RA and vitamin A) in liver, oxidative stress and the hepatic injury in a rat model of com-mon bile duct ligation (CBDL)-induced liver injury were investigated. Female rats were subjected to a sham (n=5) or CBDL (n=48). Two weeks after operation, rats undergoing CBDL were randomized to receive treatment with either ATRA at three different doses (0.1, 1.5, 7.5 mg/kg) dissolved in bean oil or only bean oil every day over a 4-week experimental period. Rats were killed and blood samples were collected from the heart for determination of the serum transaminase. The contents of retinoids in rat liver were detected by using HPLC. Malondialdehyde (MDA), glutathione (GSH) and superox-ide dismutase (SOD) levels in liver were determined by a spectrophotometric method according to the instruction of the kits. Liver pathologic changes were observed under the light microscopy and electron microscopy. The results showed that compared with sham-operated group, the levels of reti-noids in the liver tissue were significantly decreased in the CBDL group (P<0.01). ATRA (0.1 mg/kg) administration in CBDL rats partially restored the contents of retinoids (P<0.05). Liver RA and vita-min A contents in CBDL group were significantly increased after ATRA (1.5 and 7.5 mg/kg) sup-plementation as compared with sham-operated group (P<0.05). However, in ATRA-treated CBDL group, hepatic GSH level and SOD activity, depressed by CBDL, and hepatic MDA level, increased by CBDL were returned to those in sham-operated group (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). Treatment with ATRA could reduce levels of serum transaminase as compared with sham-operated group, more greatly in 1.5 and 7.5 mg/kg ATRA-treated groups than in 0.1 mg

  20. The Effect of Sodium Butyrate in Combination with ATRA on the Proliferation/Differentiation of SKM-1

    Institute of Scientific and Technical Information of China (English)

    黄梅; 刘文励; 李春蕊; 邓金牛; 周剑锋; 张东华; 孙汉英

    2004-01-01

    To explore the molecular mechanisms of sodium butyrate working on SKM-1 cell proliferation/differentiation and to study its synergistic effect with all-trans retinoic acid (ATRA), SKM1 cells were grown in the absence or presence of sodium butyrate and/or ATRA. The percentage of viable cells was determined by trypan blue exclusion. Differentiation was determined by nitroblue tetrazolium (NBT) reduction and cell surface adhesion molecules was analyzed by FACS. Cell cycle distribution was examined after DNA staining by propidium iodide. D-type cyclins, cdks and P21 mRNA were studied by reverse transcription-polymerase chain reaction. Our results showed that sodiun butyrate and/or ATRA blocked cells mainly in the G0/G1 phase of the cell cycle. ATRA inhibited the mRNA expression of CDK6, CDK4, cyclinD3 and cyclinD1. Sodium butyrate inhibited the mRNA expression of CDK2, cyclinD2 and cyclinD1. ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Both ATRA and/or sodium butyrate stimulated p21 expression at the mRNA levels. Our results suggest that the effect of sodium butyrate on cell proliferation/differentiation might be linked to its ability to induce expression of p21 mRNA and inhibit the cyclin-cdk complexes. Our observations support the notion that the sodium butyrate works synergistically with ATRA.

  1. Tratamiento adaptado al riesgo de la leucemia promielocítica aguda con ATRA y quimioterapia

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    Montesinos Fernández, Pau

    2016-01-01

    El tratamiento actual de la leucemia promielocítica aguda (LPA) con la combinación de ácido trans-retinóico (ATRA) y quimioterapia proporciona una tasa muy elevada de curaciones. No obstante, aunque estrecho, hay un margen de mejora mediante la reducción de cada una de las diferentes causas de fracaso terapéutico. Dada la heterogeneidad de estas causas de fracaso, planteamos la hipótesis de que un análisis de dichas causas y la identificación de las variables ligadas al paciente, a su enferm...

  2. ÚLCERAS ESCROTALES SECUNDARIAS A TRATAMIENTO CON ÁCIDO TRANSRETINOICO (ATRA

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    Cuevas-Ruiz MV

    2011-01-01

    Full Text Available El ácido trans retinoico es el fármaco de elección en el tratamiento de la Leucemia Promielocítica Aguda. El efecto secundario más grave del fármaco es el síndrome de diferenciación, pero puede ocasionar lesiones en piel y úlceras escrotales. Presentamos el caso de un varón con leucemia promielocítica aguda que recibió ATRA y presentó úlceras escrotales

  3. ÚLCERAS ESCROTALES SECUNDARIAS A TRATAMIENTO CON ÁCIDO TRANSRETINOICO (ATRA)

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    Cuevas-Ruiz MV; Jiménez-Alfaro C; Cuevas-Ruiz B

    2011-01-01

    El ácido trans retinoico es el fármaco de elección en el tratamiento de la Leucemia Promielocítica Aguda. El efecto secundario más grave del fármaco es el síndrome de diferenciación, pero puede ocasionar lesiones en piel y úlceras escrotales. Presentamos el caso de un varón con leucemia promielocítica aguda que recibió ATRA y presentó úlceras escrotales

  4. Antifungal effect of Sticophus hermanii and Holothuria atra extract and its cytotoxicity on gingiva-derived mesenchymal stem cell

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    Kristanti Parisihni

    2013-12-01

    Full Text Available Background: Sea cucumber had been acknowledged to have some medical properties Sticophus hermanii and Holothuria atra are species of sea cucumber which has been known to have antifungal properties thus potentially explored as therapeutic agent in oral candidiasis. Purpose: The aim of this study was to examine the antifungal property Sticophus hermanii and Holothuria atra extract against Candida albicans and its cytotoxicity to human gingiva-derived mesenchymal stem cell. Methods: The study was an experimental laboratories research with post test only control group design. Methanolic extract of Sticophus hermanii and Holothuria atra in concentrations of 1%, 0.5%; 0.25%; 0.13%, 0.07%; 0.03%, 0.02% and 0.01%; were tested its cytotoxicity on gingiva-derived mesenchymal stem cell. Cell viability were measured by MTT assay. The antifungal property against Candida albicans was tested by disk diffusion method. Data were analyzed by ANOVA followed by LSD. Results: Extract of Sticophus hermanii showed no cytotoxicity in all concentrations (p>0.05, while Holothuria atra showed toxicity in the concentration of 1% and not cytotoxic in the concentrations below (p<0.05. Both sea cucumber extract could inhibit the growth Candida albicans, in vitro, proved by the clear zone around the disc in all concentrations (p<0.05. Conclusion: Stichopus hermanii and Holothuria atra extract had the antifungal effect against Candida albicans. Sea cucumber extract were not cytotoxic togingiva-derived mesenchymal stem cell in the concentration of Sticophus hermanii ≤ 1% and Holothuria atra ≤ 0.5%.Latar belakang: Teripang telah diketahui mempunyai berbagai khasiat medis. Sticophus hermanii dan Holothuria atra adalah spesies teripang yang telah diketahui mempunyai sifat anti jamur sehingga santat potensial untuk diekplorasi sebagai agen terapeutik pada infeksi di rongga mulut. Tujuan: Tujuan dari penelitian ini adalah untuk meneliti sifat anti jamur ekstrak Sticophus hermanii

  5. Isolation and Characterization of Microsatellite Loci in the Chinese Cobra Naja atra (Elapidae

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    Xiang Ji

    2011-07-01

    Full Text Available We characterize thirteen polymorphic microsatellite loci isolated from Naja atra genomic libraries, which were enriched for AC-motif microsatellites. The thirteen loci were screened on a group of 48 individuals from two populations, one in Yong’an and the other in Ganzhou. These markers revealed a relatively high degree of genetic diversity (4–12 alleles per locus and heterozygosity (Ho ranged from 0.213–0.854 and He ranged from 0.301–0.838. Tests for departure from Hardy-Weinberg equilibrium and for linkage disequilibrium were conducted for each of the two populations separately. After sequential Bonferroni correction, none of the 13 loci showed significant departures from Hardy-Weinberg equilibrium. Hierarchical analysis of molecular variance indicated that a small but significant (P < 0.001 proportion (16.0% of the total variation in the microsatellite DNA data were attributable to differences among populations, indicating geographical structuring and restricted gene flow. It could be attributable to the Wuyi mountains in the area having a sufficiently isolating effect to significantly reduce gene flow. Our microsatellite data also showed a low Nm (1.31 value in the two populations from mainland China. Thus, the Yong’an and Ganzhou populations could be treated as distinct evolutionarily significant units (ESUs. The high level of polymorphism revealed by these microsatellite markers will be useful for the study of gene flow, population structure and evolutionary history of N. atra.

  6. Low-dose ATRA Supplementation Abolishes PRM Formation in Rat Liver and Ameliorates Ethanol-induced Liver Injury

    Institute of Scientific and Technical Information of China (English)

    PAN Zhihong; DAN Zili; FU Yu; TANG Wangxian; LIN Jusheng

    2006-01-01

    The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 μg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A,RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 μg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling,steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER).ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation

  7. Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

    Science.gov (United States)

    Narvekar, Mayuri M.

    The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.

  8. Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

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    J. C. Troiano

    2006-01-01

    Full Text Available A comparative study on the sensitivity of erythrocytes from different vertebrate species (avian, mammalian and reptilian to the hemolytic action caused by cardiotoxin isolated from Naja naja atra venom was carried out. Cardiotoxin was able to induce direct hemolysis in washed erythrocytes from several animals, except for llama. The EC50 values from hemolysis of the most sensitive (cat and the most resistant (snake animal varied approximately tenfold. According to the cell behavior, it was possible to characterize four types of behavior: The first was observed in cat, horse and human cells; the second in rat, rabbit and dog erythrocytes; and the third only in llama erythrocytes, which were resistant to cardiotoxin concentrations up to 300 µg/ml. Finally, avian and reptilian erythrocytes were more resistant to cardiotoxin III-induced hemolysis than those of the mammalian species.

  9. Status of ATR-A1 irradiation experiment on vanadium alloys and low-activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Gomes, I.; Smith, D.L. [Argonne National Lab., IL (United States); Matsui, H. [Tohoku Univ. (Japan)

    1996-10-01

    The ATR-A1 irradiation experiment was a collaborative U.S./Japan effort to study at low temperature the effects of neutron damage on vanadium alloys. The experiment also contained a limited quantity of low-activation ferritic steel specimens from Japan as part of the collaboration agreement. The irradiation started in the Advanced Test Reactor (ATR) on November 30, 1995, and ended as planned on May 5, 1996. Total exposure was 132.9 effective full power days (EFPDs) and estimated neutron damage in the vanadium was 4.7 dpa. The vehicle has been discharged from the ATR core and is scheduled to be disassembled in the next reporting period.

  10. Purification, characterization and primary structure of a chymotrypsin inhibitor from Naja atra venom.

    Science.gov (United States)

    Zhou, Xing-Ding; Jin, Yang; Lu, Qiu-Min; Li, Dong-Sheng; Zhu, Shao-Wen; Wang, Wan-Yu; Xiong, Yu-Liang

    2004-02-01

    A chymotrypsin inhibitor, designated NA-CI, was isolated from the venom of the Chinese cobra Naja atra by three-step chromatography. It inhibited bovine alpha-chymotrypsin with a Ki of 25 nM. The molecular mass of NA-CI was determined to be 6403.8 Da by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) analysis. The complete amino acid sequence was determined after digestion of S-carboxymethylated inhibitor with Staphylococcus aureus V8 protease and porcine trypsin. NA-CI was a single polypeptide chain composed of 57 amino acid residues. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. NA-CI shared great similarity with the chymotrypsin inhibitor from Naja naja venom (identities=89.5%) and other snake venom protease inhibitors. PMID:14990218

  11. Laboratory experiments on membrane filter sampling of airborne mycotoxins produced by Stachybotrys atra corda

    Science.gov (United States)

    Pasanen, A.-L.; Nikulin, M.; Tuomainen, M.; Berg, S.; Parikka, P.; Hintikka, E.-L.

    A membrane filter method for sampling of airborne stachybotrystoxins was studied in the laboratory. Toxigenic strains of Stachybotrys atra on wallpaper, grain, hay and straw were used as toxin sources in the experiments. Air samples were collected on cellulose nitrate and polycarbonate membrane filters at air flow rates of 10-20 ℓ min -1. After the filter sampling, the air was passed through methanol. The results showed that stachybotrystoxins (trichothecenes) were concentrated in airborne fungal propagules, and thus can be collected on filters. Polycarbonate filters with a pore size of 0.2 μm collected the highest percentage of toxic samples. The laboratory experiments indicated that polycarbonate filter sampling for the collection of airborne mycotoxins is a promising method for extension to field measurements.

  12. Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis

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    Stanojković Tatjana P

    2011-10-01

    Full Text Available Abstract Background The aim of this study is to investigate in vitro antioxidant, antimicrobial and anticancer activity of the acetone extracts of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. Methods Antioxidant activity was evaluated by five separate methods: free radical scavenging, superoxide anion radical scavenging, reducing power, determination of total phenolic compounds and determination of total flavonoid content. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method against six species of bacteria and ten species of fungi. Anticancer activity was tested against FemX (human melanoma and LS174 (human colon carcinoma cell lines using MTT method. Results Of the lichens tested, Lecanora atra had largest free radical scavenging activity (94.7% inhibition, which was greater than the standard antioxidants. Moreover, the tested extracts had effective reducing power and superoxide anion radical scavenging. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. Extract of Cladonia furcata was the most active antimicrobial agent with minimum inhibitory concentration values ranging from 0.78 to 25 mg/mL. All extracts were found to be strong anticancer activity toward both cell lines with IC50 values ranging from 8.51 to 40.22 μg/mL. Conclusions The present study shows that tested lichen extracts demonstrated a strong antioxidant, antimicrobial and anticancer effects. That suggest that lichens may be used as as possible natural antioxidant, antimicrobial and anticancer agents to control various human, animal and plant diseases.

  13. CLONING PROMOTER OF HUMAN SATB1 GENE AND EFFECT OF ATRA AND CoCl2 ON ITS ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the structure and activity of SATB1 promoter in different cells, ATRA and CoCl2 effect on its activity. Methods Using luciferase system to assay the promoter activity of human SATB1 gene, three luciferase reporter vectors were constructed which driven by different regions of 5' untranslated sequence from human SATB1 gene, called pGL3-SP2946-luc, pGL3-SP1718-luc and pGL3-SP751-luc, and transfected into Jurkat T, K562, U937 and Hela cells transiently using lipofectinamine, the expression activity was detected at different dosage of ATRA and CoCl2 treatment for different time course. Results The reporter gene expression from SATB1 promoter were high activity in U937 cell, moderate in Jurkat T cell, low activity in K562 cell and showed no obvious activity in Hela cell, the reporter gene expression from pGL3-SP751-luc kept on the higher lever in Jurkat T, K562 and U937 cells than the other two vectors. We also found that the repressive effect of CoCl2 on SATB1 's mRNA expression and the relative luciferase expression from pGL3-SP751-luc in U937 cell was down-regulated obviously by ATRA and CoCl2 in the concentration- and time-dependent manners. Conclusion SATB1 promoter drives gene expression with cell-specificity and its core promoter region maybe exist in the - 751 ~ - 9bp of 5' untranslated region of human SATB1 gene. Combined with the experiment result we found before that SATB1 was down-regulated by ATRA in U937, the results imply that STAB1 maybe is down-regulated by ATRA and CoCl2 through its promoter in the differentiation of myeloid cell line-U937.

  14. Discovery, structural characterization and functional analysis of alpha-2-macroglobulin, a novel immune-related molecule from Holothuria atra.

    Science.gov (United States)

    Qian, Jing; Ren, Chunhua; Xia, Jianjun; Chen, Ting; Yu, Zonghe; Hu, Chaoqun

    2016-07-10

    The non-specific protease inhibitor alpha-2-macroglobulin (A2M) is a key macromolecular glycoprotein that involved in host immune defense against pathogens in vertebrates and invertebrates. However, no research regarding A2M has been developed in echinoderms to date. In this study, the full-length cDNA of A2M was cloned from the sea cucumber (Holothuria atra), which is a tropical species widely distributed along the coasts of the South China Sea and designated HaA2M. HaA2M possesses all three conserved functional domains of known A2M proteins, including the bait region domain, thioester domain and receptor-binding domain. Compared to fish and shrimp A2Ms, the histidine residue from the catalytical regions is well conserved in HaA2M. HaA2M mRNA was predominantly expressed in coelomocytes and, to a lesser extent, in the body wall, intestine and respiratory tree. A2M activity was detected in the coelomic fluids of H. atra. The mRNA expression and activity levels were investigated in the major immune tissues and coelomic fluids of H. atra after challenge with inactivated Vibrio alginolyticus or polyriboinosinic polyribocytidylic acid [Poly (I: C)]. RNA interference (RNAi)-mediated knockdown of HaA2M resulted in a significant reduction of HaA2M gene transcript level (86%). RNAi-mediated silencing of HaA2M gene significantly decreased the A2M activity (38%) and increased the number of viable bacteria (2.8-fold) in the coelomic fluids of H. atra infected by V. alginolyticus. Our study, as a whole, supplied the evidences for HaA2M as an immune-relevant molecule and it might have multiple functions in the innate immune system of H. atra. PMID:27033585

  15. Effect of All-Trans Retinoic Acid (ATRA on Viability, Proliferation, Activation and Lineage-Specific Transcription Factors of CD4+ T Cells

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    Katayoon Bidad

    2011-12-01

    Full Text Available All-trans retinoic acid (ATRA, as an active metabolite of vitamin A, has been shown to affect immune cells. This study was performed to evaluate the effect of ATRA on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells. CD4+ T cells were  separated  from  heparinized  blood  of  healthy  donors  and  were  cultured  in conditions, some with, some without ATRA.Viability was assessed by PI  flowcytometry and proliferation was measured by MTT assay. CD69 expression was determined by flowcytometry as a measure of cell activation. Lineage-specific transcription  factors  (FOXP3,  RORγt  and  T-bet  were  examined  by intracellular staining and flowcytometry. High doses of ATRA (0.1-1 mM caused extensive cell death in both PBMCs and CD4+ T cells. Doses of ATRA equal to or lower than 10 µM did not  adversely affect cell viability and proliferation in comparison to  culture medium without ATRA.Doses of ATRA between 10 µM and 1nM significantly increased cell activation when compared  to  culture medium without  ATRA. ATRA could increase FOXP3+  and also FOXP3+RORγt+ T cells while it decreased RORγt+ and T-bet+ T cells. This study showed that doses of ATRA up to 10 µM are safe when using with CD4+  T cells in terms of cell viability, proliferation and activation.We  could  also  show  that  ATRA  diverts  the  human  immune  response  in  neutral conditions (without adding polarizing cytokines by increasing FOXP3+  cells and decreasing RORγt+  cells. ATRA could be regarded as a potential therapy in inflammatory conditions and autoimmunities.

  16. Antitumor and Antifungal Activities of Organic Extracts of SeacucumberHolothuria atra from the Southeast Coast of India

    Institute of Scientific and Technical Information of China (English)

    Devaraj Isaac DHINAKARAN; Aaron Premnath LIPTON

    2015-01-01

    In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu-cumberHolothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such asTrichoderma viride, Aspergillus niger,Aspergillus flavis,Candida albicansandPenicillium chrysogenum. Relatively high antifungal activity was seen againstCandida albicans at 100µL−1 concentration of extracts. Zone of inhibition was measured at 18mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated withH. atra extract at concentrations 0.078−10mgmL−1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber (H. atra)showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

  17. Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

    Science.gov (United States)

    Narvekar, Mayuri M.

    The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (pretinoic acid to treat highly resistant ovarian cancer.

  18. Age-related Variation in Snake Venom:Evidence from Two Snakes (Naja atra and Deinagkistrodon acutus) in Southeastern China

    Institute of Scientific and Technical Information of China (English)

    Ying HE; Jianfang GAO; Longhui LIN; Xiaomei MA; Xiang JI

    2014-01-01

    In this study we explored electrophoretic proifles, enzymatic activities and immunoreactivity of neonate and adult venoms from two snakes (Naja atra and Deinagkistrodon acutus) coexisting in southeastern China. Age-related variation in electrophoretic proifles was found in both species and proteolytic and ifbrinogenolytic activity was higher in neonate than adult venoms. Neonate D. acutus venom had higher 5' nucleotidase, PLA2, hyaluronidase and gelatinolytic activity, but lower esterolytic activity, than adult venom. Neonate and adult D. acutus venoms showed identical phosphomonoesterase, LAO and ifbrinolytic activities. Neonate N. atra venom had higher phosphomonoesterase and LAO activity, but lower 5' nucleotidase, PLA2, hyaluronidase and AchE activities than adult venom. Neonate and adult N. atra venoms showed similar gelatinolytic activity. Further, age-dependent immunoreactivity was found in both species, and cross-reactions between homologous venoms and antiserums were closely related to venom composition. We speculate that age-related variation in venom characteristics is possibly driven by evolutionary forces associated with ontogenetic shifts in dietary habits, competition and predation pressure.

  19. STUDY ON EFFECTS OF RED ORPIMENT AND ATRA ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate PML gene and protein expression and localization in leukemia cell lines. Methods Cell morphology was assayed by Wright's stain and fluorescence stain, and PML mRNA ex- pression by RT-PCR, PML protein localization by immuno-fluorescence. Results NB4 and HL-60 cells dif- ferentiated morphologically after treatment with anti-retinoic acid ( ATRA ) while K562 cells did not differenti- ate. Typical apoptosis was found in each cell line after treatment with red orpiment. Immuno-fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and the PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with red orpiment , the fusion protein disappeared in NB4 cells, then degraded, which was also seen in HL-60 cells and K562 cells. The expression of PML mRNA was not changed in all three cell lines after treatment with ATRA or red orpi- ment. Conclusion PML plays the role of differentiation and apoptosis inducer in leukemia cells at the trans- lational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.

  20. Decitabine and SAHA-Induced Apoptosis Is Accompanied by Survivin Downregulation and Potentiated by ATRA in p53-Deficient Cells

    Directory of Open Access Journals (Sweden)

    Barbora Brodská

    2014-01-01

    Full Text Available While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA in leukemic cell line CML-T1, reactive oxygen species (ROS generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere-related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization.

  1. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

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    Cao-Xin Chen

    2015-01-01

    Full Text Available Cardiotoxin (CTX from Naja naja atra venom (NNAV reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.

  2. Naja naja atra Venom Protects against Manifestations of Systemic Lupus Erythematosus in MRL/lpr Mice

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    Jiali Zhu

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration of Naja naja atra venom (NNAV had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg or Tripterygium wilfordii polyglycosidium (10 mg/kg daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.

  3. Effects of a fraction from Naja naja atra venom on transplanted hepatic carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    XuT; LiuZT

    2002-01-01

    The effects of a fraction from Naja naja atra venom(FNNAV) on inhibiting the growing of hepatic carcinoma and inducing the apoptosis of hepatic carcinoma were studied.It showed that the weight of transplants of hepatic carcinoma was lower both in middle and high concentration FNNAV groups compared with the control group after ten days treatment with FNNAV,and the nude mice of high concentration FNNAV group lived longer than those of the control group.It has been found that the expression of bcl-2 gene in transplants of hepatic carcinoma in FNNAV groups was decreased by using SABC method.By counting the peripheral blood WBC and bone marrow cells it proved that FNNAV did not affect the function of bone marrow in a short period.These results suggest that FNNAV has the anti-tumor effects on transkplanted hepatic carcinoma in nude mice and could prolong the life of mice bearing the tumor.No inhibitory effect of FNNAV on bone marrow was observed.

  4. Influence of all-trans retinoic acid(ATRA) on the expression of NANOG in Glioma cell lines

    Institute of Scientific and Technical Information of China (English)

    Liu Weixian; Yi Fuxin

    2012-01-01

    Objective To investigate the effects of all-trans retinoic acid(ATRA) on the expression of NANOG in glioma cell lines.Methods Each cell line was divided into the experimental group which was treated with ATRA for 5 days,and the control group which was cultured normally without ATRA treatment. Immunocytochemistry and RT-PCR were adopted to detect the expression of NANOG at protein and mRNA level among the three kinds of cell lines. Results Positive rates of NANOG protein in glioma cell lines SHG-44,U87 MG and U251 in control groups were (65.5±3.0)%,(64.8±8.0)% and (64.5±1.2)%, respectively, and the difference was not statistically significant(F=0.190,P=0.829). NANOG mRNA of the three cell lines in the relative content were 0.636 8±0.039 9, 0.642 1±0.063 7, 0.651 6±0.044 4,and the difference was not statistically significant(F=0.427,P=0.662).However,5 days after application of ATRA-induced NANOG protein in the three cell lines,the positive rates of NANOG protein of experimental groups were (36.5±7.3)%,(35.5±7.9)%,(35.2±6.1)%,respectively,compared with the control groups,the differences were statistically significant (FSHG-44=259.1,FU87=129.5,FU251= 431.8,PSHG-44=0.0,PU87=0.0,PU251=0.0),and the relative level of NANOG mRNA in these groups were 0.458 3±0.079 1,0.255 1±0.079 3 and 0.333 1±0.054 0,respectively,compared with the control groups,the difference was significant(FSHG-44=77.8,FU87=277.9,FU251=398.1,PSHG-44=0.0,PU87=0.0,PU251=0.0).Conclusion NANOG which highly expressed in glioma cell line SHG-44,U87 MG and U251 can be reduced by ATRA.

  5. Disease Progression, Response to ACEI/ATRA Therapy and Influence of ACE Gene in IgA Nephritis

    Institute of Scientific and Technical Information of China (English)

    Keng-Thye Woo; Yeow-Kok Lau; Yi Zhao; Fang-E Liu; Hwee-Boon Tan; Eng-Keng Tan; Fook-Chong Stephanie; Choong-Meng Chan; Kok-Seng Wong

    2007-01-01

    Various studies have shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (ID) polymorphism may play a role in the progression to end stage renal failure (ESRF) in patients with IgA nephritis (IgAN). In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62±5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine (p<0.001), lower proteinuria (p<0.002) and fewer numbers progressing to ESRF (p<0.002). Among patients with genotype Ⅱ, there were less ESRF in the treatment group when compared to the untreated control group (p<0.02). The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype Ⅱ.The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.

  6. Microstructural examination of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Microstructural examination results are reported for four heats of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment to {approximately}4 dpa at {approximately}200 and 300 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment or composition.

  7. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Ding

    2014-01-01

    Full Text Available Previous studies reported the oral administration of Naja naja atra venom (NNAV reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  8. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

    Science.gov (United States)

    Ding, Zhi-Hui; Xu, Li-Min; Wang, Shu-Zhi; Kou, Jian-Qun; Xu, Yin-Li; Chen, Cao-Xin; Yu, Hong-Pei; Qin, Zheng-Hong; Xie, Yan

    2014-01-01

    Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180  μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  9. Metabolic Characterization of All-Trans-Retinoic Acid (ATRA)–Induced Craniofacial Development of Murine Embryos Using In Vivo Proton Magnetic Resonance Spectroscopy

    OpenAIRE

    Feifei Qin; Zhiwei Shen; Lihong Peng; Renhua Wu; Xiao Hu; Guishan Zhang; Shijie Tang

    2014-01-01

    AIM: To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA)-induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11) with all-trans-retinoic acid (ATRA). Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone....

  10. Tensile and impact properties of vanadium-base alloys irradiated at low temperatures in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Nowicki, L.J.; Billone, M.C.; Chung, H.M.; Smith, D.L. [Argonne National Lab., IL (United States)

    1998-03-01

    Subsize tensile and Charpy specimens made from several V-(4-5)Cr-(4-5)Ti alloys were irradiated in the ATR-A1 experiment to study the effects of low-temperature irradiation on mechanical properties. These specimens were contained in lithium-bonded subcapsules and irradiated at temperatures between {approx}200 and 300 C. Peak neutron damage was {approx}4.7 dpa. Postirradiation testing of these specimens has begun. Preliminary results from a limited number of specimens indicate a significant loss of work-hardening capability and dynamic toughness due to the irradiation. These results are consistent with data from previous low-temperature neutron irradiation experiments on these alloys.

  11. A short-chain α-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the analgesia induced by cobrotoxin (CT) from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 μg/kg), intra-cerebral venticularly (2.4 μg/kg) or microinjected into periaqueductal gray ( PAG, 1.2 μg/kg). The antinociceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im or 10 mg/kg, ip) or naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 μg/kg, ip) exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 μg/kg (1/23th of a systemic dose) produced marked analgesic effects. Microinjection of CT 1.2 μg/kg ( 1/46th of systemic dose) into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg (im) or naloxone at 3 mg/kg (ip) failed to block the analgesic effects of CT, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception (75 μg/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT' analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

  12. Changes in Sediment Fatty Acid Composition during Passage through the Gut of Deposit Feeding Holothurians: Holothuria atra (Jaeger, 1883) and Holothuria leucospilota (Brandt, 1835).

    Science.gov (United States)

    Mfilinge, Prosper L; Tsuchiya, Makoto

    2016-01-01

    Sea cucumbers Holothuria atra and Holothuria leucospilota play an important role in the bioturbation of sediment in coral reef and rocky intertidal ecosystems. This study investigated changes in sediment fatty acid (FA) composition during gut passage in H. atra and H. leucospilota. The FA composition did not differ significantly between species. Comparison of FA composition in ambient sediment (AS), foregut (FG), midgut (MG), hindgut (HG), and faecal pellets (FPs) indicated that marked changes in FA composition occurred during passage through the gut of H. atra and H. leucospilota. Saturated fatty acids (SAFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and branched fatty acids (BrFAs) were significantly higher in FG than in AS, suggesting that both species selectively ingested nutrient rich particles. Significant reduction of SAFAs, MUFAs, PUFAs, and BrFAs occurred in MD and HD, with complete elimination of most PUFAs in FPs. A decrease in PUFAs 20:5ω3, 18:4ω3, 22:5ω3, 22:6ω3, 18:2ω6, 18:3ω3, 18:3ω6, odd-numbered BrFAs, and MUFA 18:1ω7 indicated that algal detritus and bacteria were important part of diet. These results have implications for the fate of specific dietary FAs, especially ω3 and ω6, and the contribution holothurian FPs make to the FA composition of coral reef and rocky intertidal ecosystems. PMID:27042355

  13. Changes in Sediment Fatty Acid Composition during Passage through the Gut of Deposit Feeding Holothurians: Holothuria atra (Jaeger, 1883 and Holothuria leucospilota (Brandt, 1835

    Directory of Open Access Journals (Sweden)

    Prosper L. Mfilinge

    2016-01-01

    Full Text Available Sea cucumbers Holothuria atra and Holothuria leucospilota play an important role in the bioturbation of sediment in coral reef and rocky intertidal ecosystems. This study investigated changes in sediment fatty acid (FA composition during gut passage in H. atra and H. leucospilota. The FA composition did not differ significantly between species. Comparison of FA composition in ambient sediment (AS, foregut (FG, midgut (MG, hindgut (HG, and faecal pellets (FPs indicated that marked changes in FA composition occurred during passage through the gut of H. atra and H. leucospilota. Saturated fatty acids (SAFAs, monounsaturated fatty acids (MUFAs, polyunsaturated fatty acids (PUFAs, and branched fatty acids (BrFAs were significantly higher in FG than in AS, suggesting that both species selectively ingested nutrient rich particles. Significant reduction of SAFAs, MUFAs, PUFAs, and BrFAs occurred in MD and HD, with complete elimination of most PUFAs in FPs. A decrease in PUFAs 20:5ω3, 18:4ω3, 22:5ω3, 22:6ω3, 18:2ω6, 18:3ω3, 18:3ω6, odd-numbered BrFAs, and MUFA 18:1ω7 indicated that algal detritus and bacteria were important part of diet. These results have implications for the fate of specific dietary FAs, especially ω3 and ω6, and the contribution holothurian FPs make to the FA composition of coral reef and rocky intertidal ecosystems.

  14. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    Directory of Open Access Journals (Sweden)

    Kou-Zhu Zhu

    2013-01-01

    Full Text Available To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg, the native NNAV (untreated with heat; 90 μg/kg, and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

  15. Regulation of CD11b transcription by decreasing PRC2 and increased acH4 level during ATRA-induced HL-60 differentiation

    Institute of Scientific and Technical Information of China (English)

    Huarong Tang; Fangping Chen; Qian Tan; Sanqin Tan; Linxin Liu; Fan Zhang

    2009-01-01

    Polycomb repressive complex 2 (PRC2),which mediates trimethylation of lysine 27 on histone H3 (K27me3),plays an important role in many types of stem cell differentiation.Here,we try to reveal how PRC2,PRC2-mediated repressive histone marker H3K27me3,and active histone marker histone H4 acetylation (acH4) regulate the CD11b transcription during all-trans retinoic acid (ATRA)-induced HL-60 leukemia cell differentiation.By using quantitative real-time polymerase chain reaction (qPCR) and western blot analysis,we found that the mRNA and protein expression levels of two members of PRC2 were decreased during ATRA-induced HL-60 differentiation,respectively.When treated with ATRA for 72 h,the EZH2 and SUZ12 mRNA levels were decreased to 35% and 38% of the control group,respectively.At the same time,the granulocytic mature surface marker CD11b expression was increased significantly at mRNA level detected by qPCR and protein level detected by flow cytometry.By using chromatin immunoprecipita-tion assay,we compared the local changes in SUZ12 binding and PRC2-mediated H3K27me3 at the promo-ter of CD11b during ATRA-induced HL-60 differ-entiation.Both the levels of SUZ12 binding and PRC2-mediated H3K27me3 at the promoter of CD11b were decreased for 4.1 and 3.8 folds,respectively.And we also found the increase in the acH4 level up to 4 folds after 72 h of ATRA treatment.These results suggested that the histone modification including PRC2-mediated repressive histone marker H3K27me3 and active histone marker acH4 may involve in CD11b transcription during HL-60 leukemia cells reprogram-ming to terminal differentiation.

  16. Combination of nanoparticle-delivered siRNA for Astrocyte elevated gene-1 (AEG-1) and all-trans retinoic acid (ATRA): an effective therapeutic strategy for hepatocellular carcinoma (HCC)

    Science.gov (United States)

    Rajasekaran, Devaraja; Srivastava, Jyoti; Ebeid, Kareem; Gredler, Rachel; Akiel, Maaged; Jariwala, Nidhi; Robertson, Chadia L.; Shen, Xue-Ning; Siddiq, Ayesha; Fisher, Paul B.; Salem, Aliasger K.; Sarkar, Devanand

    2016-01-01

    Hepatocellular carcinoma (HCC) is a fatal cancer with no effective therapy. Astrocyte elevated gene-1 (AEG-1) plays a pivotal role in hepatocarcinogenesis and inhibits retinoic acid-induced gene expression and cell death. Combination of a lentivirus expressing AEG-1 shRNA and all-trans retinoic acid (ATRA) profoundly and synergistically inhibited subcutaneous human HCC xenografts in nude mice. We now have developed liver-targeted nanoplexes by conjugating poly(amidoamine) (PAMAM) dendrimers with polyethylene glycol (PEG) and lactobionic acid (Gal) (PAMAM-PEG-Gal) which were complexed with AEG-1 siRNA (PAMAM-AEG-1si). The polymer conjugate was characterized by 1H-NMR, MALDI and mass spectrometry, and optimal nanoplex formulations were characterized for surface charge, size and morphology. Orthotopic xenografts of human HCC cell QGY-7703 expressing luciferase (QGY-luc) were established in the livers of athymic nude mice and tumor development was monitored by bioluminescence imaging (BLI). Tumor-bearing mice were treated with PAMAM-siCon, PAMAM-siCon+ATRA, PAMAM-AEG-1si and PAMAM-AEG-1si+ATRA. In the control group the tumor developed aggressively. ATRA showed little effect due to high AEG-1 levels in QGY-luc cells. PAMAM-AEG-1si showed significant reduction in tumor growth and the combination of PAMAM-AEG-1si+ATRA showed profound and synergistic inhibition so that the tumors were almost undetectable by BLI. A marked decrease in AEG-1 level was observed in tumor samples treated with PAMAM-AEG-1si. The group treated with PAMAM-AEG-1si+ATRA nanoplexes showed increased necrosis, inhibition of proliferation and increased apoptosis when compared to other groups. Liver is an ideal organ for RNAi therapy and ATRA is an approved anti-cancer agent. Our exciting observations suggest that the combinatorial approach might be an effective way to combat HCC. PMID:26079152

  17. Atração e desligamento voluntário de jovens empregados: um estudo de caso no setor jornalístico

    Directory of Open Access Journals (Sweden)

    Lucia Barbosa de Oliveira

    2014-12-01

    Full Text Available Neste estudo de caso de natureza exploratória, desenvolvido em uma grande empresa do setor jornalístico, o objetivo foi analisar fatores de atração e perda de jovens que voluntariamente optaram por deixar a organização. A fundamentação teórica para a pesquisa foi construída a partir dos seguintes pilares: aspirações de trabalho e carreira da chamada geração Y, fatores de atração e retenção e cultura organizacional, tendo em vista a identificação da necessidade de adaptação da cultura da empresa aos novos desafios estratégicos e competitivos que vem enfrentando. O levantamento de dados foi feito por meio de 17 entrevistas em profundidade com jovens da geração Y que pediram demissão após pelo menos um ano de estágio e/ou trabalho na empresa. Como principais fatores de atração, destacaram-se a imagem e a reputação do principal jornal da empresa, que muito contribui para a construção de sua marca empregadora. Por outro lado, alguns traços da cultura organizacional apresentaram contraste com aspectos valorizados pelos participantes, indicando incongruência de valores, que pode estar levando a organização a perder jovens talentos, considerados importantes ante a necessidade de renovar seu quadro funcional e sua cultura. Com relação às motivações pessoais para deixar a empresa, foram identificados três grupos de jovens – idealistas, carreiristas e imediatistas –, orientados por anseios e perspectivas profissionais distintos.

  18. Recombinant expression of a GH12 β-glucanase carrying its own signal peptide from Stachybotrys atra in yeast and filamentous fungi.

    Science.gov (United States)

    Picart, Pere; Orejas, Margarita; Pastor, F I Javier

    2016-08-01

    The β-glucanase Cel12A gene from Stachybotrys atra has been cloned and heterologously expressed in Aspergillus nidulans and Saccharomyces cerevisiae. The recombinant strains constructed, contained the exonic sequence of cel12A including its own signal peptide coding sequence. SDS-PAGE and zymography revealed that recombinant Cel12A has a molecular mass of 24 kDa which agrees with that deduced from its amino acid sequence, indicating that it is expressed in the non-glycosylated active form. Recombinant A. nidulans showed about eightfold greater activity yield than S. cerevisiae recombinant strain, namely 0.71 and 0.09 β-glucanase Units/ml of culture, respectively. In both host strains most of the activity was secreted to the extracellular media, evidencing the functionality of Cel12A signal peptide in yeast and fungi. This novel signal peptide might facilitate the expression and efficient secretion of other recombinant proteins difficult to secrete. PMID:27339304

  19. Metabolic characterization of all-trans-retinoic acid (ATRA-induced craniofacial development of murine embryos using in vivo proton magnetic resonance spectroscopy.

    Directory of Open Access Journals (Sweden)

    Feifei Qin

    Full Text Available AIM: To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA-induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (1H-MRS. METHODS: Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11 with all-trans-retinoic acid (ATRA. Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone. Using an Agilent 7.0 T MR system and a combination of surface coil coils, a 3 mm×3 mm×3 mm 1H-MRS voxel was selected along the embryonic craniofacial tissue. 1H-MRS was performed with a single-voxel method using PRESS sequence and analyzed using LCModel software. Hematoxylin and eosin was used to detect and confirm cleft palate. RESULT: 1H-MRS revealed elevated choline levels in embryonic craniofacial tissue in the RA70 and RA100 groups compared to controls (P<0.05. Increased choline levels were also found in the RA70 and RA100 groups compared with the RA30 group (P<0.01. High intra-myocellular lipids at 1.30 ppm (IMCL13 in the RA100 group compared to the RA30 group were found (P<0.01. There were no significant changes in taurine, intra-myocellular lipids at 2.10 ppm (IMCL21, and extra-myocellular lipids at 2.30 ppm (EMCL23. Cleft palate formation was observed in all fetuses carried by mice administered 70 and 100 mg/kg RA. CONCLUSIONS: This novel study suggests that the elevated choline and lipid levels found by 1H-MRS may represent early biomarkers of craniofacial defects. Further studies will determine performance of this test and pathogenetic mechanisms of craniofacial malformation.

  20. Características y resultado a largo plazo de pacientes mayores con leucemia promielocítica aguda tratados con esquemas terapéuticos basados en ATRA más antraciclinas

    OpenAIRE

    Martínez Cuadrón, David

    2015-01-01

    La leucemia promielocítica aguda (LPA) es un subtipo de leucemia mieloide aguda que se diferencia por una morfología característica y la presencia de la t(15;17) y su correspondiente reordenamiento molecular PML/RARa. Clínicamente, no es infrecuente que se presente con coagulopatía, pudiendo ser la responsable de la muerte del paciente incluso antes del diagnóstico. No obstante, su buena respuesta al tratamiento con ácido holo-trans retinoico (ATRA) se ha traducido en una importante mejoría d...

  1. Atração e penetração de Meloidogyne javanica e Heterodera glycines em raízes excisadas de soja Attraction and penetration of Meloidogyne javanica and Heterodera glycines in excised soybean roots

    Directory of Open Access Journals (Sweden)

    Hercules Diniz Campos

    2011-09-01

    Full Text Available Com vista ao estudo de atração e penetração de Meloidogyne javanica (Treub Chitwood e Heterodera glycines (Ichinoe em soja (Glycine max L., desenvolveu-se uma técnica empregando-se segmento de raiz com 2cm de comprimento. Nos segmentos de raiz de soja infectados, observou-se que a penetração de juvenis de segundo estádio (J2 de M. javanica ocorre pela coifa seguida de migração entre os feixes vasculares do cilindro central. Juvenis de H. glycines penetraram, aproximadamente, 15mm da coifa. A região seccionada da raiz de soja atraiu três vezes mais J2 de M. javanica do que a região da coifa, mas esta não foi tão atrativa para J2 de H. glycines. A obstrução conjunta da coifa e do local seccionado reduziu (83% a penetração de J2, tanto de M. javanica quanto de H. glycines. Quando apenas um desses locais foi obstruído, a outra extremidade livre compensou o processo atrativo. Portanto, as substâncias atrativas são liberadas por essas extremidades. A penetração de J2 de M. javanica foi maior no segmento de raiz quando comparada com a plântula intacta de soja. Entretanto, os J2 de H. glycines penetraram menos em segmentos de raiz e em plântulas sem folhas, quando comparados com plântulas intactas e com as seccionadas no colo. Portanto, na cultivar de soja "Embrapa 20", a atração e os locais de penetração de J2 de H. glycines e M. javanica são diferenciados. Esta técnica poderá ser útil nos estudos de atração e penetração de outros nematoides endoparasitas.To study the attraction and penetration of Meloidogyne javanica (Treub Chitwood and Heterodera glycines (Ichinoe in soybean (Glycine max L., a technique using 2-cm long root segments was developed. In infected soybean root segments penetration of second stage juveniles (J2 of M. javanica occured through the root cap following migration between the vascular bundles of the central cylinder. Juveniles of H. glycines penetrated about 15mm from the root cap. The cut

  2. The Effects of All-Trans Retinoic Acid (ATRA) on the Expression of Ski in Cultured Rat Mesangial Cells Treated by TGF-β1%Ski在全反式维甲酸抑制TGF-β1诱导的系膜细胞增殖中的作用

    Institute of Scientific and Technical Information of China (English)

    苏宝凤; 王晓花; 张莉; 于莹; 陈晓岚

    2013-01-01

    目的 探讨全反式维甲酸(ATRA)对转化生长因子(TGF)-β1诱导的大鼠系膜细胞增殖及Ski表达的影响.方法 不同浓度ATRA预处理大鼠HBZY-I系膜细胞(为各剂量ATRA组)24 h后再加TGF-β1(10 μg/L)培养24 h.CCK-8法检测细胞增殖情况;Real-time PCR法检测Ski mRNA的表达;Western blot检测Ski蛋白的表达;激光共聚焦荧光显微镜检测Ski蛋白的亚细胞定位.并与正常对照组及TGF-β1组比较.结果 与正常对照组相比,TGF-β1组系膜细胞增殖明显,且Ski mRNA及蛋白表达升高(P<0.05);与TGF-β1组相比,ATRA能够呈剂量依赖性地抑制TGF-β1的促增殖作用,ATRA 10 μmol/L组Ski mRNA及蛋白表达量明显增高.ATRA组Ski蛋白主要定位于大鼠系膜细胞核,其细胞核荧光信号强度较TGF-β1组明显增强,细胞浆中荧光信号强度较TGF-β1组减弱.结论 ATRA可通过上调大鼠系膜细胞Ski表达,抑制其向核外转位,从而抑制TGF-β1诱导的系膜细胞增殖.%Objective To investigate the effects of all-trans retinoic acid (ATRA) on the expression of Ski in cultured rat mesangial cells treated by transforming growth factor (TGF-β1).Methods The mesangial cells were pre-treated with different concentrations of ATRA for 24 h, and then stimulated with TGF-β1 (10 μg/L) for 24 h.The cell proliferation was detected by CCK-8 method.The Ski mRNA expression was determined by real time-PCR.The protein expression of Ski was determined by Western blot analyses.The localization of Ski was observed by confocal fluorescence microscopy.Results Compared with the control group, TGF-β1 significantly enhanced the proliferation and the expression of Ski mRNA and protein in rat mesangial cells (P < 0.05).ATRA significantly inhibited mesangial cell proliferation induced by TGF-β1 in a dose-dependent manner.In ATRA groups, Ski mRNA and protein were increased significantly.Additionally, Ski protein was mainly localized in nucleus, and fluorescence intensity was

  3. ATRA对三阴性乳腺癌细胞CDH1表达的影响%Effect of ATRA on CDH1 Expression in Triple-negative Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    陈卓荣; 沈三弟; 黄湛; 赵欣; 雷睿文

    2012-01-01

    目的 探讨全反式维甲酸(ATRA)对三阴性乳腺癌(TNBC)细胞系MDA-MB-231的CDH1表达的影响及可能机制.方法 实验分空白对照组(control)、5-杂氮-2'-脱氧胞苷(5-Aza-CdR)组及ATRA组,分别用甲基化特异性PCR(MSP)、逆转录PCR(RT-PCR)方法检测MDA-MB-231细胞CDH1基因启动子区甲基化状态及mRNA表达情况.结果 空白对照组MDA-MB-231细胞CDH1基因启动子区处于甲基化状态,CDH1mRNA无表达,而5-Aza-CdR组与ATRA组CDH1基因启动子区处于非甲基化状态,CDH1 mRNA表达明显上调,且两组之间无明显差别.结论 ATRA能够通过去甲基化机制上调MDA-MB-231细胞CDH1基因的表达.

  4. A Gestão de Pessoas e as Estratégias de Atração, Desenvolvimento e Retenção de Profissionais: O Caso Petrobras

    Directory of Open Access Journals (Sweden)

    Nildes Pitombo Leite

    2013-12-01

    Full Text Available Este estudo de caso, ancorado na abordagem qualitativa e com nível de análise organizacional, investigou a gestão de pessoas dentro de unidades com estruturas organizacionais remotas (i.e., longe dos centros urbanos e não remotas da PETROBRAS – Petróleo Brasileiro S/A. A pesquisa foi realizada em três plataformas marítimas, três bases e na unidade operacional da selva Amazônica, envolvendo 31 respondentes, entre diretores, gerentes, profissionais de RH, supervisores e coordenadores. Esses respondentes são representativos para o nível de análise escolhido, bem como para a estratégia de pesquisa. Seu foco esteve voltado para dois problemas principais, considerados igualmente relevantes: Como gerenciar pessoas em unidades distantes das principais sedes da organização? Como gerenciar essas pessoas de modo a assegurar os objetivos estratégicos de atrair, desenvolver e reter o capital humano valorizado nessas unidades? A coleta dos dados primários foi feita por meio de entrevistas em profundidade e observações; a dos dados secundários, por meio de análise de documentos. Trabalhou-se com as estratégias das análises de conteúdo, documental e reflexiva. Seus resultados indicaram as especificidades de políticas e práticas de gestão de pessoas, oriundas das estratégias de atração, desenvolvimento e retenção de profissionais nessas unidades, especificidades essas que representam contribuição para a área de gestão de pessoas. DOI:10.5585/riae.v12i4.2043

  5. 抗蛇毒血清滴眼治疗眼镜蛇毒致眼外伤%Antivenom Eye-drop for Treatment of Ocular Injury by Cobra (Naja naja atra) Venom Poisoning

    Institute of Scientific and Technical Information of China (English)

    李其斌; 龚坚; 宋观志; 覃军; 赵晓琴

    2004-01-01

    目的观察单价抗眼镜蛇毒血清溶液滴眼治疗中华眼镜蛇毒(Naja naja atra,Chinese cobra)不慎进入眼睛引起外伤中毒性急性角膜炎的临床效果.方法观察1992~2002年我院急诊救治眼镜蛇喷毒或加工蛇毒时不慎蛇毒进入眼睛引起外伤性急性角膜炎8例男性病人,从受伤到就诊时间最快15min,最慢50min.就诊后立即用生理盐水冲洗受伤眼睛,紧接着给予单价抗眼镜蛇毒血清溶液滴入患眼0.5h后,用氯霉素眼药水、可的松(或地塞米松)眼药水交替滴眼,直至痊愈.结果使用抗蛇毒血清滴眼后局部疼痛、异物感等症状在20min内得到缓解,3天内眼睑红肿、结膜充血等角膜炎症状消失.8例病人均治愈,未留有后遗症.结论:单价抗眼镜蛇毒血清滴眼治疗中华眼镜蛇毒致眼外伤是非常方便有效的方法,可能与其能迅速中和眼睛内残留的蛇毒有关.

  6. 广东眼镜蛇毒低分子量多肽的分离纯化与性质鉴定%Purification and Characterization of Low Molecular Weight Polypeptides from the Venom of Guangdong Cobra (Naja Naja Atra)

    Institute of Scientific and Technical Information of China (English)

    郝彩; 韩丽萍; 蒋琳兰; 江伟健

    2011-01-01

    目的 从广东眼镜蛇粗毒中分离纯化出色谱纯的低分子量多肽并对其部分性质进行鉴定.方法 采用化学沉淀法对蛇粗毒进行预处理,经 Sephadex G-50 凝胶过滤和 UND Sphere S 阳离子交换层析得到高纯度低分子量多肽,用SDS-PAGE及HPLC对产物纯度进行鉴定,并用SDS-PAGE和质谱法测定分子量,采用蛙心灌流法考察产物是否具有心脏毒性.结果 结果表明,经分离纯化后得到两种低分子量多肽GI2和GI3,均为单一组分,可达到色谱纯,SDS-PAGE法测得GI2分子量为14 300 Da,质谱法测得GI3分子量为6 725.8 Da,仅GI2具有心脏毒性,收率分别为9.5%和10.1%.结论 通过化学沉淀预处理,并经2次柱色谱可从广东眼镜蛇毒中分离得到两种色谱纯的低分子量多肽,且收率较高.%OBJECTIVE To isolate and characterize some properties of the chromatographically pure low molecular weight polypeptides from the venom of Guangdong cobra (Naja naja atra). METHODS Isolation and purification were carried out by chromatography on Sephadex G-50 and UND Sphere S column after the pretreatment by chemical precipitation. The purity of this product was determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and HPLC, and its molecular weight was observed by SDS-PAGE and mass spectrography. The cardiotoxicity of the polypeptides was investigated using the frog heart perfusion experiment. RESULTS After the chemical precipitation and Two-step column chromatography, the products, named ‘GI2’ and ‘GI3’, were single components. The molecular weight of GI2 is 14 300 Da observed by SDS-PAGE and GI3 is 6 725.8 Da determined by mass spectrography. The yields of the products were 9.5% and 10. 1%, and only GI2 showed cardiotoxicity. CONCLUSION Two low molecular weight components could be obtained from the venom of Guangdong cobra after chemical precipitation and two-step column chromatographies, with high yield.

  7. Attraction of Neomegalotomus parvus (Westwood(Heteroptera: alydidae to cow urine and ammonia Atração de Neomegalotomus parvus (Westwood (Heteroptera: alydidae por urina de vaca e amônia

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    Jovenil José da Silva

    2010-02-01

    Full Text Available The alydid bug parvus (Westwood is not easily detected in the field and the discovery of attractants may be a suitable way to monitor this species. The attraction of N. parvus to traps (transparent, transparent green and yellow baited with cow urine and ammonia was studied in two field trials. Traps were placed near a terrace with pigeon pea plants (Cajanus cajan L.. Tap water, NaCl 10% aqueous solution (w/v, cow urine, and ammonia (NH4OH 1% aqueous solution were tested as attractants in yellow, transparent and transparent green traps. Green traps baited with cow urine caught more bugs than yellow and transparent traps (3.2 and 7.2 times more, respectively, and more bugs than traps of the same color with just water (no captures or NH4OH solution (14.5 times more. Traps baited with ammonia caught more bugs than traps with water: 14.4, 4.7 and 6.7 times more than transparent green, yellow, and transparent traps, respectively, or NaCl solution: 3.9, 7.6 and 6.2 times, respectively. Both ammonia and cow urine are attractive to N. parvus and may be tested to monitor the bugs in the field.O percevejo alidídeo Neomegalotomus parvus (Westwood não é facilmente detectado no campo e a descoberta de atraentes pode ser uma forma adequada para monitorar a espécie. A atração de N. parvus a armadilhas (transparentes, verde transparente e amarela iscadas com urina de vaca e amônia foi estudada em dois experimentos em campo. Armadilhas foram colocadas próximas a um terraço com plantas de feijão-guandu (Cajanus cajan L.. Água corrente, solução aquosa de NaCl 10% (p/v, urina de vaca e amônia (solução aquosa de NH4OH 1% foram testadas como atraentes em armadilhas amarelas, transparentes e transparentes verdes foram utilizadas. Armadilhas verdes iscadas com urina capturaram mais insetos do que armadilhas amarelas e transparentes (3,2 e 7,2 vezes mais, respectivamente, e mais insetos do que armadilhas da mesma cor com apenas água (zero insetos ou solu

  8. Atração de miracídios de Schistosoma mansoni por hospedeiros invertebrados: comportamento de miracídios frente a girinos de Hyla fuscovaria Miracidia attraction to invertebrate hosts: miracidia behavior in the presence of Hyla fuscovaria girina

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    Beatriz de C. Brasio

    1985-02-01

    Full Text Available Analisou-se a atração de miracídios de Schistosoma mansoni das linhagens BH e SJ frente a seus vetores simpátricos e alopátricos tendo-se em consideração a possibilidade da presença de substâncias quimiotáxicas emanadas dos moluscos. Estudou-se também o comportamento desses miracídios frente a girinos de Hyla fuscovaria. Foi verificado que houve atração dos miracídios pelos moluscos vetores e que essa atração foi mais evidente quando a larva era colocada frente ao seu hospedeiro simpátrico.As observações realizadas no decorrer da experiência demonstraram a presença de substâncias miraxonais emanadas pelos moluscos.Miracidia tropism to suitable hosts is a subject of much controversy. In this work, we try to determine the possible specificity of Schistosoma mansoni miracidia attraction and also the degree of this specificity. To this end an experiment was carried out to determine the probability of attraction in a given experimental set up, to H. fuscovaria girina or to one of two susceptible snail species. Two strains of S. mansoni were employed and also the corresponding snail species. A specially designed apparatus consisting of two circular glass chambers joined by an open channel was used. One of the girina or a snail was placed in one of the chambers (randomly chosen. In the channel a known number of miracidia were deposited and the count of miracidia in each of the three compartments (the two chambers and the channel was recorded. The experiment was carried out under strong or subdued lighting. Statistical and ad-hoc exploratory data analysis have shown that: a the miracidia, when exposed to only one species of snail, show more attraction to the sympatric snail host; bone strain of miraciadia showed more attraction under strong lighting; the other strain behaved the opposite way, with stronger attraction under weak liht; c the girina did not attract the miracidia; this seems to imply that sone chemiotropism is present

  9. A história da ciência na formação do professor de física: subsídios para um curso sobre o tema atração gravitacional visando às mudanças de postura na ação docente History of Science in teaching education: suggestions for a course plan on gravitational attraction aiming to change teachers' attitudes

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    Sandra Regina Teodoro Gatti

    2004-12-01

    Full Text Available O objetivo desta pesquisa foi estudar como a evolução histórica dos modelos de atração entre corpos, tendo como pano de fundo a evolução dos modelos de mundo, pode auxiliar na formação inicial do docente de Física. Para tanto, sugerimos um planejamento de curso sobre o tema atração gravitacional, destinado principalmente a docentes de Física que atuam no ensino médio. O planejamento do curso foi baseado: em dados sobre a evolução dos modelos de mundo, buscando evidenciar como o conceito de atração gravitacional desenvolveu-se historicamente; nas concepções alternativas mais comuns encontradas na literatura, incluindo um breve esboço de noções diagnosticadas em uma amostra de docentes de Física de ensino médio; e em sugestões de leituras de resultados de pesquisas recentes sobre os processos de ensino e aprendizagem de ciências. Pretende-se fornecer aos docentes elementos de reflexão que lhes proporcionem mudanças de postura, através do questionamento da visão de ciência enquanto processo de construção e sobre sua própria prática de ensino. Partindo de resultados recentes da pesquisa em Ensino de Ciências, a metodologia sugerida privilegia o trabalho coletivo, com a realização de debates e sínteses. As atividades mencionadas são acompanhadas de justificativas sobre a escolha do tema e objetivos.The main purpose of this research was to study how the attraction among bodies, having as background the evolution of models of the world, can help prospective teachers' education. To reach this goal, we suggest a course plan on gravitational attraction, addressed mainly to High School Physics teachers. This course was based: on data about world models' evolution, searching to make clear how the concept of gravitational attraction was historically developed; on the most common alternative conceptions found in the literature, including a brief outline of notions found among in-service High School Physics teachers

  10. 中华眼镜蛇心脏毒素(CardiotoxinⅢ)的克隆及其在大肠杆菌和酵母中的表达%Molecular Cloning and Expression of Cardiotoxin Ⅲ from Naja naja atra in E.coli and Yeast Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    陈兴勇; 吕萍; 刘兢; 徐康森

    2008-01-01

    Chinese cobra (Naja naja atra) cardiotoxins are three-fingered family with 60~62 amino acids bind by four disulfide bonds. CardiotoxinⅢ (CTXⅢ) is one of the major toxic component which can cause hemolysis and cytotoxicity. However, there is no report on the fusion expression of CTXⅢ in soluble form so far. The cloning, expression and purification of recombinant CTX Ⅲ (rCTXⅢ) from Naja naja atra in E. coli and in yeast Pichia pastoris were reported here. CTXⅢ gene, fused with enterokinase in E.coli His-patch Thioredoxin expression system, were expressed in soluble form and released by osmotic-shock treatment. CTX Ⅲ gene was also cloned and expressed in the methylotropic yeast Pichia pastoris pPIC9K expression vector in the first time. The yield of the secretion level was 9.5 mg/L. Using straightforward one-step chromatography procedure, the rCTXⅢ, with three additional amino acids (GYT) at the N-terminal site, was purified to a purity of more than 90% and recovery yield of 65%. The purified rCTX Ⅲ was further characterized by cytotoxic assay with IC50 4.66μg/ml. An effective expression and purification system for recombinant CTXs in P. pastoris was developed, this system will permit us the ready isolation of active cardiotoxins. This protocol can also be easily used for the production of the toxin in a larger scale with low cost.%心脏毒素cardiotoxinⅢ (CTXⅢ)是中华眼镜蛇毒主要组分之一,根据Genbank中已有的CTXs序列设计特异性引物,从中华眼镜蛇毒中克隆出208bp的CTXⅢ片段,并将该基因片段分别克隆至大肠杆菌His-patch ThioredoxinB载体中,重组CTXⅢ经渗透休克分泌至胞外.将CTXⅢ基因插入酵母pPIC9K分泌型表达载体重组表达,N端带有3个氨基酸(GYT)残基的重组CTXⅢ(rCTXⅢ)分泌量达9.5mg/L,经一步凝胶过滤纯化,其纯度达90%以上,纯化率达65%.经细胞毒性实验检测,纯化的rCTXⅢ 12h的IC50为4.66μg/ml,证实重组蛋白具有良好的生物学活性.

  11. 全反式维甲酸与紫杉醇、阿霉素联合诱导HL-60细胞凋亡的研究%Studies on the apoptosis using ATRA in combination with taxol and ADR in HL-60 cell lines

    Institute of Scientific and Technical Information of China (English)

    尤学芬; 丁润生; 谢玉娟; 姚登福; 陆德炎

    2007-01-01

    目的:探讨全反式维甲酸(ATRA)分别与紫杉醇(Taxol)、阿霉素(ADR)单独或联合孵育HL-60细胞株能否增强凋亡诱导作用,并进一步研究bcl-2基因及家族bax、bcl-x基因在此过程中的作用.方法:①用台盼兰拒染法观察细胞生长活力;②在光镜和电镜下观察细胞形态变化;③用流式细胞仪(FCM)检测药物孵育前后细胞凋亡率(AP)的变化;④用RT-PCR法检测药物孵育前后bcl-2基因及其家族bax、bcl-x基因的表达水平.结果:①ATRA能增强Taxol和ADR对HL-60细胞的生长抑制作用;②ATRA能增强HL-60细胞对Taxol和ADR诱导的细胞凋亡;③在ATRA与Taxol、ADR联合诱导的HL-60细胞凋亡中,bcl-2、bcl-xl基因表达下降,bax、bcl-xs基因表达增加.结论:ATRA能增加Taxol和ADR对HL-60细胞的生长抑制作用及凋亡诱导作用,bcl-2基因及家族bax、bcl-x基因参与了ATRA与Taxol、ADR联合诱导细胞凋亡的调控.

  12. Effect of Atra on the Expression of CyclinD3 and Lipoprotein-associated phospholipase A2 in injury nidus of carotid endothelium in rabbits%ARTA对兔颈动脉内膜损伤病灶CydinD3及LP-PLA2的影响

    Institute of Scientific and Technical Information of China (English)

    胡真真; 董果雄; 张社华; 张滨; 姚如永

    2012-01-01

    目的 观察全反式维甲酸(ARTA)对兔颈动脉内膜损伤与修复病灶内膜增生和细胞周期素CyclinD3及炎性相关因子LP-PLA2表达的影响和机制.方法 将54只健康新西兰大白兔随机分为9组(n=6):正常对照组(A、B、C)、高脂饮食组(A、B、C)、治疗组(A、B、C).普通饮食后正常对照组仅暴露颈动脉;高脂饮食组,暴露颈动脉并损伤内膜;治疗组用ARTA灌胃,其他操作同高脂饮食组.术后1周、2周、4周处死A、B、C组动物,对病变血管行形态学观察和测定,分别用ELISA和免疫组化方法检测颈动脉内膜损伤与修复病灶中LP-PLA2和CyclinD3的表达水平.结果 ①正常对照组LP-PLA2仅有微量表达.CyclinD3胞浆呈弱阳性表达,胞核呈阴性表达.②高脂饮食组在术后7天内膜开始增生,28天后明显增生,出现泡沫细胞、脂质条纹、管腔狭窄.LP-PLA2和CyclinD3表达水平较正常组显著增高.③治疗组LP-PLA2和CyclinD3表达水平明显低于高脂饮食组(P<0.05).内膜的增生和管腔的狭窄显著减轻(P<0.05).结论 ARTA可以通过抑制LP-PLA2和CyclinD3的表达,抑制内膜的炎症反应和血管平滑肌细胞的增生,从而抑制颈动脉内膜损伤病灶的过度增生和管腔狭窄.%Objective To observe the influence of all-trans retinoic acid( ATRA) on the process of neointimal formation and the expression of CyclinD3 and Lipoprotein-associated phos pholipase A2 in injury nidus of carotid endothelium in rabbits. Methods Fifty-six healthy male New-Zealand rabbits were randomly divided in to 9 groups(=6): normal control groups(A, B, C), high-fat groups(A, B, C), treatment groups(A, B, C). There were 6 rabbits in each group. The normal control groups were fed with conventional chow, and underwent surgery without endothelium injury. The high-fat groups were fed with high cholesterol chowand. subjected to the carotid endothelial injury by air desiccation. The treatment groups were administered ATRA

  13. Fluxos de capitais internacionais de investidores institucionais para o Brasil: um estudo sobre os fatores de atração e de repulsão Flow of international capital of institutional investors to Brazil: a study of push and pull factors

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    Antônio André Cunha Callado

    2005-06-01

    Full Text Available Os fluxos de capitais internacionais direcionados para o Brasil têm sido bastante significativos. O objetivo desta pesquisa foi identificar os principais fatores de influência sobre os fluxos obtidos através dos Investidores Institucionais estrangeiros. Avaliou-se a influência dos fatores de atração (relacionados ao Brasil e dos fatores de repulsão de capital (relacionados ao ambiente econômico externo sobre esses fluxos. Os dados mensais (de janeiro de 1993 a outubro de 2001 foram coletados no Banco Central do Brasil, FGVDADOS, IBGE e Moody's. Utilizou-se um modelo de correção de erro para avaliar as relações de curto e longo prazos. A variável explicativa que obteve o melhor resultado para o longo prazo foi o spread médio relativo ao risco soberano do Brasil emitido pela agência Moody's. Para o curto prazo, os resultados não se mostraram significativos. O spread relativo ao risco revelou-se importante em sua perspectiva associada à capacidade e intenção que um devedor possui de honrar seus compromissos financeiros de longo prazo, bem como à percepção sobre o risco de inadimplência.There was a sharp increase in the flow of international capital to Brazil in the decade of 1990 after the debt crisis of the previous decade. An analysis of the factors influencing the flow of capital of institutional investors in the decade of l990 was made to evaluate the pull factors, related to the domestic scene, and the push factors, related to the global scene. Data was collected monthly between January 1993 and October 2001 from the Banco Central do Brasil, FGVDADOS, IBGE and Moody's. Over the long term the variable that best explained capital flow was the average spread related to the sovereign risk of Brazil as defined by Moody's. No significant conclusion was found for the short term. The average spread related to risk was crucial considering the perspective associated to the future qualification and willingness of the bond issuer to

  14. Preparation and in vitro characterization of ATRA loaded mPEG-PLA diblock copolymeric micelles%维甲酸/聚乙二醇-聚乳酸二嵌段共聚物胶束的制备及其体外性质

    Institute of Scientific and Technical Information of China (English)

    李媛; 齐宪荣

    2008-01-01

    目的:制备甲氧基聚乙二醇一聚乳酸[methoxyl poly(ethylene glycol)-poly(lactic acid),mPEGPLA]二嵌段共聚物及其载全反式维甲酸(all-trans-retinoic acid,ATRA)的胶束,验证共聚物的结构,并考察胶束的形态、粒径、载药量、包封率、体外释放特性及其溶血性质.方法:采用辛酸亚锡催化的开环聚合法制备不同嵌段比例的mPEG-PLA二嵌段共聚物,用核磁共振氢谱(1HNMR)和傅利叶红外光谱(FTIR)验证其结构,凝胶渗透色谱(GPC)考察其相对分子质量及分布.用透析法、丙酮溶剂蒸发法及丙酮挥发透析法制备空白及载ATRA胶束.透射电子显微镜(TEM)观察胶束的形态,动态光散射仪(DLS)测定其粒径分布.采用紫外分光光度法测定胶束的载药量和包封率,并研究其体外释放性质及溶血性质.结果:制备了5种不同嵌段比例的mPEG-PLA共聚物,TEM结果显示ATRA胶束呈类球形.胶束的粒径及载药量受制备方法、药物/嵌段共聚物比例以及嵌段共聚物性质的影响,通过筛选得到丙酮挥发透析法及嵌段共聚物/药物的比例为5:2为最适制备条件,得到胶束的平均粒径在267.5~431.8 nm内,并随着嵌段共聚物疏水部分的增大而增加;胶束的载药量在11.23%~20.01%内,包封率为31.79%~56.57%,也具有随疏水嵌段增大而增加的趋势.载药胶束在PBS一乙醇(9:1)的释放液中48 h体外累积释药率为61.6%~94.1%,载药胶束与50%血浆混合后药物释放趋于零级,药物的释放随聚合物相对分子质量的减小和载药量的减小而增加.100~150mg·L-1的载药胶束无溶血现象,而5 mg·L-1的ATRA溶液即出现溶血.结论:通过研究嵌段比例对mPEGPLA嵌段共聚物载ATRA胶束一系列体外性质的影响,为选择最适的嵌段共聚物比例提供了依据.载药量,体外释放及溶血性质结果显示mPEG-PLA嵌段共聚物载ATRA胶束具有明显的增溶,缓释作用,并能够减少药物的毒副作用.

  15. Orchid bee baits attracting bees of the genus Megalopta (Hymenoptera, Halictidae in Bauru region, São Paulo, Brazil: abundance, seasonality, and the importance of odors for dim-light bees Abelhas do gênero Megalopta (Hymenoptera, Halictidae atraídas por iscas químicas usadas para euglossíneos na região de Bauru, SP: abundância, sazonalidade e importância de odores para abelhas crepusculares

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    Fátima R. N. Knoll

    2012-12-01

    Full Text Available Nocturnal bees in the genus Megalopta Smith, 1853 are generally collected using artificial light sources. However, between 1993 and 2000, a total of 946 females (no males were captured were captured using aromatic baits commonly used for orchid bees (Euglossini in five localities in Bauru region, São Paulo, Brazil. Aromatic compounds used in bait traps were: benzyl acetate, eucalyptol, eugenol, skatole, methyl salicylate, and vanillin. The Megalopta species collected were: M. guimaraesi (71.2% of total number of specimens, M. amoena (28.1%, and M. aegis (0.6%. Using the data from these traps, we showed that there was a positive and significant correlation between the abundance of individuals and meteorological factors, rainfall and temperature. Bees were more commonly collected in the spring (September to December and summer (December to March than in the autumn and winter, the latter characterized for being a drier and colder period. Variations in the abundance were also detected among localities and years. The most attractive compounds were eugenol (54%, methyl salicylate (22%, and eucalyptol (16%. The ability to detect smells may have an important role in searching for flowers during dim-light conditions. We suggest the use of aromatic compounds in future studies on the biology of Megalopta in the Neotropical region.Abelhas noturnas do gênero Megalopta (Smith, 1853 são geralmente coletadas usando fontes artificiais de luz. Porém entre os anos de 1993 e 2000, um total de 946 fêmeas de Megalopta foram capturadas (machos não foram capturados usando iscas aromáticas frequentemente usadas para atração de machos de Euglossini, em cinco localidades na região de Bauru, São Paulo, Brasil. Os compostos aromáticos utilizados foram: acetato de benzila, eucaliptol, eugenol, escatol, salicilato de metila e vanilina. As espécies encontradas foram M. guimaraesi (71.2% do total de indivíduos, M. amoena (28.1% and M. aegis (0.6%. De modo geral

  16. ATR-A1 irradiation experiment on vanadium alloys and low activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tasi, H.; Strain, R.V.; Gomes, I.; Hins, A.G.; Smith, D.L.

    1996-04-01

    To study the mechanical properties of vanadium alloys under neutron irradiation at low temperatures, an experiment was designed and constructed for irradiation in the Advanced Test Reactor (ATR). The experiment contained Charpy, tensile, compact tension, TEM, and creep specimens of vanadium alloys. It also contained limited low-activation ferritic steel specimens as part of the collaborative agreement with Monbusho of Japan. The design irradiation temperatures for the vanadium alloy specimens in the experiment are {approx}200 and 300{degrees}C, achieved with passive gap-gap sizing and fill gas blending. To mitigate vanadium-to-chromium transmutation from the thermal neutron flux, the test specimens are contained inside gadolinium flux filters. All specimens are lithium-bonded. The irradiation started in Cycle 108A (December 3, 1995) and is expected to have a duration of three ATR cycles and a peak influence of 4.4 dpa.

  17. Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

    Directory of Open Access Journals (Sweden)

    Zhao Junfeng

    2012-03-01

    Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

  18. Unhatched and Hatched Eggshells of the Chinese CobraNaja atra

    Institute of Scientific and Technical Information of China (English)

    Zheng WANG; Longhui LIN; Xiang JI

    2014-01-01

    Changes in structure and composition of the eggshell resulting from embryonic mobilization of minerals from the eggshell are found in all oviparous reptiles studied thus far. In this study, we measured samples of unhatched and hatched eggshells of the Chinese cobraNaja atrato determine the percentage of ash and the phase composition of calcium carbonate. The mean percentage of ash was signiifcantly higher in unhatched eggshells (24.6%) than in hatched eggshells (22.3%). The dominant phase in unhatched eggshells was the calcite form of calcium carbonate. In addition to the peaks of calcite, a few small peaks were found to be caused by the aragonite and vaterite phases of calcium carbonate, implying that there are small amounts of aragonite and vaterite in the eggshell. The concentration of the various phases calculated from the intensity of the X-ray diffraction spectra allowed the estimation that percentages of calcite, aragonite and vaterite were about 92%, 4% and 4%, respectively. Hatched eggshells produced similar spectral characteristics as unhatched eggshells, with one exception. The dominant phase composition in the hatched eggshell was also calcite, but the amount of the aragonite phase had a marked increase. Our study adds evidence that embryonic mobilization of minerals from the eggshell may result in changes in structure of the eggshell.

  19. A new approach for surveying the Alpine Salamander (Salamandra atra in Austria

    Directory of Open Access Journals (Sweden)

    Ursula Reinthaler-Lottermoser

    2010-12-01

    Full Text Available The Alpine Salamander is a small pitch black amphibian which is endemic to the European Alps and the Dinarides. It is strictly protected according to the European FFH guidelines. Despite its central role in the alpine ecosystem our actual published record in Austria is small. In order to resolve this shortcoming our project explores its distribution in Austria. It uses a participatory and community based approach to gather data. Everybody can enter and look at Alpine Salamander observations on our website www.alpensalamander.eu. This approach also allows us to establish an “oral history” of Salamander observations in the past 50 years by conducting interviews in the local community. Since July 2009 the website and salamander report database are online. From the actual data (more than 5600 records we already obtained an overview about the present distribution and data quality. The data are an excellent basis for detailed scientific studies on these remarkable amphibians. With this new and highly interactive approach science and education are combined to initiate protection measures with the public.

  20. Biomonitoring Climate Change and Pollution in Marine Ecosystems: A Review on Aulacomya ater

    Directory of Open Access Journals (Sweden)

    France Caza

    2016-01-01

    Full Text Available The sedentarism and wide global distribution of the blue mussel Mytilus edulis have made it a useful bioindicator to assess changes in the health status of the marine ecosystem in response to pollution and other environmental stresses. Effective biomonitoring of an ecosystem requires, however, that multiple biomarkers be used to obtain an accurate measure of the cumulative effects of different sources of environmental stress. Here, we provide a first integrated review of the biological, economical, and geographical characteristics of another species of mussels, the ribbed mussel Aulacomya ater. We discuss the use of Aulacomya ater as a complementary biomonitor to the blue mussel to assess the impact of pollutants and climate change. Recent findings have indeed shown that Mytilus edulis and Aulacomya ater have distinctive anatomy and physiology and respond differently to environmental stress. Monitoring of mixed beds containing blue and ribbed mussels may thus represent a unique opportunity to study the effect of environmental stress on the biodiversity of marine ecosystems, most notably in the Southern hemisphere, which is particularly sensitive to climate change and where both species often cohabitate in the same intertidal zones.

  1. Nucleosomal organization of chromatin in sperm nuclei of the bivalve mollusc Aulacomya ater.

    Science.gov (United States)

    Olivares, C; Ruiz, S

    1991-03-13

    The sperm nuclei of Aulacomya ater, family Mitylidae, contain three proteins (X, Aa5 and Aa6) which are specific to this cell type coexisting with a set of five somatic-type histones. Information about the chromatin structure resulting from this kind of association is scarce. Therefore, we have probed the structure of this sperm chromatin through digestion with micrococcal nuclease in combination with salt fractionation. The data obtained have allowed us to propose a nucleosomal arrangement for this chromatin. However, two types of nucleosomes would be present in agreement with their protein components. PMID:1861676

  2. Characterization of the mechanical properties of tough biopolymer fibres from the mussel byssus of Aulacomya ater.

    Science.gov (United States)

    Troncoso, O P; Torres, F G; Grande, C J

    2008-07-01

    Byssus fibres are tough biopolymer fibres produced by mussels to attach themselves to rocks. In this communication, we present the mechanical properties of the byssus from the South American mussel Aulacomya ater which have not been previously reported in the literature. The mechanical properties of the whole threads were assessed by uniaxial tensile tests of dry and hydrated specimens. Elastoplastic and elastomeric stress-strain curves were found for byssal threads from A. ater in the dry and hydrated state, respectively. The results obtained from mechanical tests were modelled using linear, power-law-type and Mooney-Rivlin relationships. These methods for dealing with tensile measurements of mussel byssus have the potential to be used with other stretchy biomaterials. PMID:18321800

  3. First report of long term measurements of the MGGL laboratory in the M\\'atra mountain range

    CERN Document Server

    Barnaföldi, G G; Cieslar, M; Dávid, E; Dobróka, M; Fenyvesi, E; Gráczer, Z; Hamar, G; Huba, G; Kis, Á; Kovács, R; Lemperger, I; Lévai, P; Molnár, J; Nagy, D; Novák, A; Oláh, L; Pázmándi, P; Piri, D; Rosinska, D; Starecki, T; Suchenek, M; Surányi, G; Szalai, S; Varga, D; Vasúth, M; Ván, P; Vásárhelyi, B; Wesztergom, V; Wéber, Z

    2016-01-01

    Matra Gravitational and Geophysical Laboratory (MGGL) has been established near Gy\\"ongy\\"osoroszi, Hungary in 2015, in the cavern system of an unused ore mine. The Laboratory is located at 88~m below the surface, with the aim to measure and analyse the advantages of the underground installation of third generation gravitational wave detectors. Specialized instruments have been installed to measure seismic, infrasound, electromagnetic noise, and the variation of the cosmic muon flux. In the preliminary (RUN-0) test period, March-August 2016, data collection has been accomplished. In this paper we describe the research potential of the MGGL, list the installed equipments and summarize the experimental results of RUN-0. A novel theoretical framework of noise damping in rock masses is also introduced. Here we report RUN-0 data, that prepares systematic and synchronized data collection of the next run period.

  4. Isomerization of all-(E)-Retinoic Acid Mediated by Carbodiimide Activation - Synthesis of ATRA Ether Lipid Conjugates

    DEFF Research Database (Denmark)

    Christensen, Mikkel Stochkendahl; Pedersen, Palle Jacob; Andresen, Thomas Lars;

    2010-01-01

    Treatment of the lysolipid 1-O-hexadecyl-sn-phosphatidylcholine with all-(E)-retinoic acid, DCC and DMAP resulted in poor acylation and caused (Z)/(E) isomerization of the alpha-beta double bond. In the presence of a proton source, the carbodiimide-activated all-(E)-retinoic acid undergoes fast i...

  5. Spectroscopic investigations on the binding of persimmon tannin to phospholipase A 2 from Chinese cobra ( Naja naja atra)

    Science.gov (United States)

    Yang, Jie; Zhong, Li; Zou, Bo; Tian, Yan; Xu, Shu-fen; Yao, Ping; Li, Chun-mei

    2012-01-01

    To understand the anti-venom mechanism of persimmon tannin, the interaction between persimmon tannin (PT) and phospholipase A 2 (PLA 2) under physiological conditions was investigated by fluorescence quenching technique in combination with Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra techniques. The results revealed that gradual fluorescence quenching was observed by titration of PLA 2 (2.0 μM) with increasing concentrations of PT (from 0 to 2.025 μM), and the type of quenching was found to be a static quenching process. Stern-Volmer plots were not linear but had an intersection at CPT ≈ 1.0 μM, indicating that PT binded to more than one class of sites on PLA 2. The binding sites calculated on basis of Scatchard plots were about 2, supporting this result. The enthalpy change (Δ H) and entropy change (Δ S) of the binding sites were -17.44 kJ/mol and 59.90 kJ/mol·, separately, suggesting that hydrophobic interaction played a main role in the binding. In addition, synchronous fluorescence, FT-IR and CD spectra showed that dramatic conformational changes in PLA 2 were induced by its interaction with PT.

  6. ¿Estan los paises europeos dando pasos atras? El caso de España y las politicas neoinjustas

    Directory of Open Access Journals (Sweden)

    Fernando Garcia Quero

    2014-01-01

    Full Text Available Este artículo aborda la crisis económica actual desde la óptica de sus consecuencias sobre la pérdida de derechos humanos en las sociedades supuestamente más desarrolladas del mundo. Situándose en el caso concreto de España, el objetivo principal del trabajo es mostrar y analizar el enorme retroceso que como resultado de la implantación paulatina de unas políticas neoinjustas, se está produciendo en los derechos humanos de segunda generación. Para ello se diferencian dos periodos históricos con implicaciones muy distintas para los derechos de la ciudadanía: el de consolidación de los Estados de Bienestar europeos (1945-1975; y el que abarca de mediados de los años 70 hasta la actualidad. Mediante un análisis documental y bibliográfico, el principal hallazgo al que se llega en este trabajo es la existencia de una relación bidireccional de retroalimentación entre un Estado de Bienestar fuerte y el cumplimiento de los derechos humanos, siendo imposible, como manifiesta la coyuntura actual española, un Estado cada vez más débil y una mejora en los derechos humanos. Se concluye que la dinámica seguida durante las últimas décadas está llevando a España a un escenario muy precario, que solo puede ser revertido a través de una ciudadanía activa que recupere su poder en las decisiones estatales.

  7. American Therapeutic Recreation Association

    Science.gov (United States)

    ... Certify a Workshop for Credit Duplicate Transcripts Higher Education ATRA Blog Chapter Affiliates ATRA Committees ATRA Task Forces ATRA Sections International RT/TR Month Member Directory Social Networking Board Calls and Member-Only Webinars Federal Public ...

  8. Elimination of vibrio cholerae, el tor, in mussels (aulacomya ater) by gamma radiation

    International Nuclear Information System (INIS)

    The D10 value of vibrio cholerae in mussels (aulacomya ater) was determined and this experiment was carried out in vivo. The D10 was 0,138 kGy, being necessary the application of 8D in mussels which is equivalent to a dose obtained from 1,102 kGy in order to remove a recount of 108 vibrios/g, quantity that causes the disease. The optimal dose for the shelf life extension of samples kept under cooling conditions (0-1oC) and examined periodically under the different analytical method criteria was 1 kGy. The shelf life time in raw mussels for the appearance feature reaches 14 days for the witness samples and 31 days for the irradiated samples at 1 kGy. The odor of the witness samples was just accepted until 12 days while the irradiated samples at 1 kGy exceeded this level reaching up to 22 days. For the cooked mussels, the odor feature was just acceptable up to 15 days in contrast to the irradiated samples at 1 kGy that reached 35 days. The shelf life for the flavor in witness samples only reached 14 days while the irradiated samples at 1 kGy were extended until 30 days. It was also studied the use of pH and nitrogenous volatile bases as quality indexes

  9. Comparative analysis of hemocyte properties from Mytilus edulis desolationis and Aulacomya ater in the Kerguelen Islands.

    Science.gov (United States)

    Caza, France; Betoulle, Stéphane; Auffret, Michel; Brousseau, Pauline; Fournier, Michel; St-Pierre, Yves

    2015-09-01

    The capability of bivalve molluscs to respond to environmental stresses largely depends upon their cellular immunity. Accordingly, shift in habitat conditions following thermal stress or exposure to pollutants may harm sensitive species differently, thereby modulating the biodiversity of a given ecosystem by favoring stress-tolerant species. Here, we have compared the sensitivity of hemocytes from Mytilus edulis desolationis (M. edulis desolationis) and Aulacomya ater (A. ater) to acute thermal stress and exposure to cadmium. The two subantarctic species are commonly found in the same habitat in the isolated Kerguelen archipelago. Our results showed that the phagocytic activity and viability of hemocytes from both species were equally sensitive to increasing concentrations of cadmium. However, although in vitro exposure to cadmium induced apoptosis in hemocytes of M. edulis desolationis and A. ater, flow cytometric analyses showed that the apoptotic profile of both species differed greatly when using Annexin V and YO-PRO-1 as apoptotic markers. We also found that the total hemocyte counts decreased strongly in A. ater but not in M. edulis desolationis following an acute thermal stress. Taken together, these results showed that stress responses differed significantly in hemocytes from both species. This suggests that the co-existence of both species may be at risk following exposure to pollutants and/or changes in temperature. PMID:26382607

  10. (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

    Science.gov (United States)

    dos Santos, G A S; Abreu e Lima, R S; Pestana, C R; Lima, A S G; Scheucher, P S; Thomé, C H; Gimenes-Teixeira, H L; Santana-Lemos, B A A; Lucena-Araujo, A R; Rodrigues, F P; Nasr, R; Uyemura, S A; Falcão, R P; de Thé, H; Pandolfi, P P; Curti, C; Rego, E M

    2012-03-01

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. PMID:21869839

  11. Educando a Estudiantes con Diversidades Linguisticas y Culturales (Educating Linguistically and Culturally Diverse Students). Que Ningun Nino se Quede Atras (No Child Left Behind).

    Science.gov (United States)

    Office of English Language Acquisition, Language Enhancement, and Academic Achievement for Limited English Proficient Students (ED), Washington, DC.

    The brochure, written in Spanish, briefly outlines the U.S. Department of Education's most recent policy on educating students with diverse linguistic and cultural backgrounds. It states the Department's mission, describes today's student population, and outlines the role of the Office of English Language Acquisition, Language Enhancement and…

  12. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium.

    Science.gov (United States)

    Binkowski, Łukasz J; Sawicka-Kapusta, Katarzyna; Szarek, Józef; Strzyżewska, Emilia; Felsmann, Mariusz

    2013-04-15

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n=60) and Coot (n=50). Free living birds were collected by hunters in years 2006-2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n=5) and high concentrations (Mallards n=18 and Coots n=17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions.

  13. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Binkowski, Łukasz J., E-mail: ljbinkowski@gmail.com [Institute of Biology, Pedagogical University of Cracow, Podbrzezie 3, 31-054 Cracow (Poland); Sawicka-Kapusta, Katarzyna, E-mail: katarzyna.sawicka-kapusta@uj.edu.pl [Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387 Cracow (Poland); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Strzyżewska, Emilia, E-mail: emijel@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Felsmann, Mariusz, E-mail: felsmann.mariusz@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland)

    2013-04-15

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n = 60) and Coot (n = 50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n = 5) and high concentrations (Mallards n = 18 and Coots n = 17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions. - Highlights: ► High levels of Cd and Pb were found in liver and kidneys of Mallard and Coot. ► Lower concentrations were found in young birds. ► Amount of metals exceeded the safety threshold established for edible poultry. ► Histopathological alterations were found in studied tissues. ► Lesions in birds with the highest concentrations of metals were numerous.

  14. Atração e desenvolvimento de Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae em cultivares de abóbora e moranga

    Directory of Open Access Journals (Sweden)

    Baldin Edson Luiz Lopes

    2002-01-01

    Full Text Available As plantas da família Cucurbitaceae são seriamente prejudicadas pelo ataque de insetos, sendo que os danos ocorrem desde a germinação até a colheita e podem ser observados em todas as partes da planta. Dentre os insetos sugadores que atacam a abóbora (Cucurbita moschata e a moranga (C. maxima, as formas jovens e adultas do percevejo Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae merecem destaque por sugarem a seiva das folhas, ramos e frutos novos, nos quais causam necroses, reduzindo a produção. Visando comparar a atratividade de plântulas de cultivares de abóbora e moranga a adultos deste percevejo e os efeitos desses materiais sobre a biologia de ninfas dessa espécie, realizaram-se ensaios sob condições de laboratório. Em teste de atratividade, o cultivar de abóbora BRA015113 destacou-se como o menos atrativo em relação ao cultivar de moranga Exposição, enquanto que o cultivar de abóbora BRA003531 foi o mais atrativo. Todos os cultivares provocaram 100% de mortalidade das ninfas, indicando a presença de componentes antibióticos, adversos ao desenvolvimento de L. gonagra.

  15. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

    International Nuclear Information System (INIS)

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n = 60) and Coot (n = 50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n = 5) and high concentrations (Mallards n = 18 and Coots n = 17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions. - Highlights: ► High levels of Cd and Pb were found in liver and kidneys of Mallard and Coot. ► Lower concentrations were found in young birds. ► Amount of metals exceeded the safety threshold established for edible poultry. ► Histopathological alterations were found in studied tissues. ► Lesions in birds with the highest concentrations of metals were numerous

  16. Encontro às escuras: sobre a atração entre as pessoas. O que mantém as pessoas unidas? (em um Projeto

    Directory of Open Access Journals (Sweden)

    Antonio Mendes Silva Filho

    2015-10-01

    Full Text Available Em toda história humana, nunca houve período com demanda tão elevada por profissionais qualificados como o atual. Os rumos da economia mundial não são, unicamente, ditados pelas nações desenvolvidas. O século 21 é centrado no conhecimento e respectiva capacidade de inovação promovida pelas pessoas, i.e., organizações (afinal, uma organização é feita de pessoas. Este é fator determinante no destino da humanidade. O futuro e respectivo domínio dependerão, primariamente, do conhecimento e a capacidade de inovação tem sido o principal propulsor deste avanço. Entretanto, para que isso aconteça numa escala maior, as pessoas são esperadas trabalharem juntas, em equipe, como um time. Mas, o que mantém as pessoas juntas perseguindo e trabalhando em pró de uma meta comum? O que poderia mover pessoas diferentes se unirem após um ‘encontro às escuras’? Este artigo discute essas questões que são determinantes ao cotidiano das pessoas e organizações, especulando e apontando respostas.

  17. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 1.- anallsis cuantitativo.

    OpenAIRE

    Juana María Coha; Elsa Sevillano C.

    2014-01-01

    Se ha determinado, cuantitativamente, presencia de organismos Coliformes y Enterococos en el molusco Aulacomya ater "choro", como índice de contaminación entérica humana, en cada etapa de su preparación hasta "cebiche". Se han pracesado 1,152 especímenes de mercados de Lima y Callao. Los resultados reportan mayores promedios de contaminación para ambos grupos m'crobianos, en choros crudos (etapa a), de mercados ubicados en zonas de menor higiene y mayor población. La temperatura ambien...

  18. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 2.- análisis cualitativo.

    OpenAIRE

    Juana Coha; Elsa Sevillano C.

    2014-01-01

    En 64 muestras (1,152 especímenes) del molusco Aulacomya ater "choro" de los mercados de Lima y Callao, se aislaron especies más representativas de tres principales grupos bacterianos: Entéricos, Enterococos y además, Micrococos. El porcentaje elevado de Escherichia coli en choros crudos (etapa a) y "cebiche" (etapa c) reafirman, como en el Estudio Cuantitativo, contaminación fecal humana; en menor cuantía, especies de Enterocococos, únicamente en choros crudos. Es notable la desi...

  19. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition

    OpenAIRE

    Eduardo Führer; Anny Rudolph; Claudio Espinoza; Rodrigo Díaz; Marisol Gajardo; Nuria Camaño

    2012-01-01

    The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L-1 (LC50-96 hours). Concentrations between 0.2 and 1.61 μg L-1 were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L-1 stimulate ammonia excretion and ...

  20. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego Littoral paleoenvironments during the beginning of the Holocene marine transgression in Lapataia Bay, Beagle Channel, National Park of Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.The Aserradero Lapataia 1 and 2 sites present clayey silty sediments including mollusk shell; Mulinia edulis, Mytilus chilensis, Aulacomya atra and Yoldia sp. Besides, dinoflagelate cysts, covers of benthonic foraminifera and copepod eggs are dominant. The microflora is represented by sporomorphs and fresh to salty water microplancton. Radiocarbon dates on Mulinia edulis shells yielded ages of 8094 ± 43 (AA74047 and 8167 ± 43 (AA74048 yr B.P. At Arroyo Baliza, clayey silts were found including Venus antiqua, Aulacomya atra, Mytilus chilensis, among others, accompanied by acritarchs and remnants of copepods. This association suggests marginal marine environments, with low to moderate salinity, and high nutrient concentration in the surface waters. Radiocarbon dating on Venus antiqua shells yielded 2844 ± 34 yr B.P. (AA74046. Marine deposits of the Aserradero

  1. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 1.- anallsis cuantitativo.

    Directory of Open Access Journals (Sweden)

    Juana María Coha

    2014-06-01

    Full Text Available Se ha determinado, cuantitativamente, presencia de organismos Coliformes y Enterococos en el molusco Aulacomya ater "choro", como índice de contaminación entérica humana, en cada etapa de su preparación hasta "cebiche". Se han pracesado 1,152 especímenes de mercados de Lima y Callao. Los resultados reportan mayores promedios de contaminación para ambos grupos m'crobianos, en choros crudos (etapa a, de mercados ubicados en zonas de menor higiene y mayor población. La temperatura ambiental en meses de verano, demuestra gran incremento de esta microflora. La temperatura de cocción de la fracción previa al "cebiche" (etapa b, efímina totalmente los contaminantes, reapareciendo Coliformes en éste (etapa el, por los aditivos. El jugo de limón no actuó como bactericida eficaz.

  2. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 2.- análisis cualitativo.

    Directory of Open Access Journals (Sweden)

    Juana Coha

    2014-06-01

    Full Text Available En 64 muestras (1,152 especímenes del molusco Aulacomya ater "choro" de los mercados de Lima y Callao, se aislaron especies más representativas de tres principales grupos bacterianos: Entéricos, Enterococos y además, Micrococos. El porcentaje elevado de Escherichia coli en choros crudos (etapa a y "cebiche" (etapa c reafirman, como en el Estudio Cuantitativo, contaminación fecal humana; en menor cuantía, especies de Enterocococos, únicamente en choros crudos. Es notable la desigualdad de frecuencia de E. coli, Streptococcus del grupo D de Lancenfield y Staphylococcus aureus entre las etapas a y e; en el que este último microorganismo se manifiesta con mayor densidad en la etapa de "cebiche", como consecuencia de la manipulación de los aditivos.

  3. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition.

    Science.gov (United States)

    Führer, Eduardo; Rudolph, Anny; Espinoza, Claudio; Díaz, Rodrigo; Gajardo, Marisol; Camaño, Nuria

    2012-01-01

    The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L(-1) (LC(50-96 hours)). Concentrations between 0.2 and 1.61 μg L(-1) were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L(-1) stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N) ratio, with respect to the control group. A. ater proved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone. PMID:22619673

  4. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition on Aulacomya ater (Molina, 1782 (Bivalvia: Mytilidae as a Criteria for Effects of Organophosphate Pesticide Exposition

    Directory of Open Access Journals (Sweden)

    Eduardo Führer

    2012-01-01

    Full Text Available The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L-1 (LC50-96 hours. Concentrations between 0.2 and 1.61 μg L-1 were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L-1 stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N ratio, with respect to the control group. A. ater proved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone.

  5. Localized Th1-, Th2-,and inflamation-associated hepatic and pulmonary immune responses in Ascaris-infected swine are increased by retinoic acid.

    Science.gov (United States)

    Pigs infected with Ascaris suum were treated with all-trans retinoic acid (ATRA) on d–1, d+1, d+3 of infection. Control or infected pigs were given 100 (LD-ATRA) or 1,000 (HD-ATRA) µg/kg ATRA in corn oil, or corn oil alone, and sacrificed at 7 and 14 days after inoculation (DAI) with infective eggs...

  6. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.

  7. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    OpenAIRE

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credi...

  8. The adhesive protein of Choromytilus chorus (Molina, 1782) and Aulacomya ater (Molina, 1782): a proline-rich and a glycine-rich polyphenolic protein.

    Science.gov (United States)

    Burzio, L A; Saéz, C; Pardo, J; Waite, J H; Burzio, L O

    2000-06-15

    The adhesive polyphenolic proteins from Aulacomya ater and Choromytilus chorus with apparent molecular masses of 135000 and 105000, respectively, were digested with trypsin and the peptides produced resolved by reversed phase liquid chromatography. About 5 and 12 major peptides were obtained from the protein of A. ater and C. chorus, respectively. The major peptides were purified by reverse-phase chromatography and the amino acid sequence indicates that both polyphenolic proteins consisted of repeated sequence motifs in their primary structure. The major peptides of A. ater contain seven amino acids corresponding to the consensus sequence AGYGGXK, whereas the tyrosine was always found as 3, 4-dihydroxyphenylalanine (Dopa), the X residue in position 6 was either valine, leucine or isoleucine, and the carboxy terminal was either lysine or hydroxylysine. On the other hand, the major peptides of C. chorus ranged in size from 6 to 21 amino acids and the majority correspond to the consensus sequence AKPSKYPTGYKPPVK. Both proteins differ markedly in the sequence of their tryptic peptides, but they share the common characteristics of other adhesive proteins in having a tandem sequence repeat in their primary structure. PMID:11004549

  9. Evidence for absorption of kelp detritus by the ribbed mussel Aulacomya ater using a new /sup 51/Cr-labelled microsphere technique

    Energy Technology Data Exchange (ETDEWEB)

    Stuart, V.; Field, J.G.; Newell, R.C.

    1983-09-15

    A modification of the /sup 51/Cr:/sup 14/C twin-labelling technique is described in which the food source is labelled with /sup 14/C but the /sup 51/Cr is enclosed in a polymeric resin membrane and presented as microspheres of a similar diameter to the food particles. This eliminates the major uptake of /sup 51/Cr which is transferred to the ctenidia and palps of the suspension-feeding mussel Aulacomya ater (Molina) from detritus labelled with /sup 51/Cr. The results suggest that although bacterial cultures based on isolates of kelp bacteria can be absorbed with an efficiency of 67 to 70%, the debris itself is also absorbed with an efficiency of approximately 50%. The kelp debris, which forms an important component of the particulate matter potentially available for consumers, may thus represent an important source of carbon for the filter feeding community adjacent to kelp beds. In contrast to the results obtained in other studies with artificial food sources, the data for kelp debris suggest that A. ater is able to maintain a positive scope for grwoth at the concentrations of suspended organic matter which occur under natural conditions in the kelp bed environment.

  10. El regreso a la escuela, Sigamos adelante: Lo que significa para las familias americanas "No dejar atras a ningun nino" (Back to School, Moving Forward: What "No Child Left Behind" Means for America's Families).

    Science.gov (United States)

    Department of Education, Washington, DC. Office of the Secretary.

    This pamphlet for parents Spanish presents the components of the "No Child Left Behind" policy of the George W. Bush administration. Prefaced with remarks by President Bush and Secretary of Education Rod Paige, the pamphlet discusses the importance of high academic standards and provides guidance for parents in interpreting test scores. The…

  11. A Gestão de Pessoas e as Estratégias de Atração, Desenvolvimento e Retenção de Profissionais: O Caso Petrobras

    OpenAIRE

    Nildes Pitombo Leite; Fabio Pitombo Leite; Lindolfo Galvão de Albuquerque

    2013-01-01

    Este estudo de caso, ancorado na abordagem qualitativa e com nível de análise organizacional, investigou a gestão de pessoas dentro de unidades com estruturas organizacionais remotas (i.e., longe dos centros urbanos) e não remotas da PETROBRAS – Petróleo Brasileiro S/A. A pesquisa foi realizada em três plataformas marítimas, três bases e na unidade operacional da selva Amazônica, envolvendo 31 respondentes, entre diretores, gerentes, profissionais de RH, supervisores e coordenadores. Esses r...

  12. Attraction of Astylus variegatus (Germ. (Coleoptera: Melyridae by volatile floral attractants Atração de Astylus variegatus (Germ. (Coleoptera: Melyridae por atraentes florais voláteis

    Directory of Open Access Journals (Sweden)

    Maurício Ursi Ventura

    2007-06-01

    Full Text Available The beetle Astylus variegatus (Germ. (Coleoptera: Melyridae is frequently found in flowers feeding on pollen. Responses of A. variegatus to volatile floral attractants were studied in common beans (Phaseolus vulgaris L. fields. Traps originally designed to capture Diabrotica speciosa (Germ. (Coleoptera: Chrysomelidae, consisted of plastic bottles (2 L with 150 holes (5-mm diameter yellow gold painted and containing inside a plastic strip (3.5 ´ 25 cm with Lagenaria vulgaris (L. powder (0.28% B cucurbitacin - feeding stimulant and arrestant for diabroticites sprayed with carbaril insecticide. Treatments consisted of 1,4-dimethoxybenzene (one or two dispensers per trap, 1,4-dimethoxybenze + indole, 1,4-dimethoxybenzene + cinnameldehyde and control. Volatile average release rates (over ten days was approximately 32 mg day-1 per dispenser under laboratory conditions. 1,4-dimethoxybenzene-lured traps caught significantly more beetles than the control, three and seven days after trap setting. Ten days after the onset of the experiment, there were no differences in number of beetles caught by treatments. Captures were higher in the 1,4-dimethoxybenzene + cinnamaldehyde treatment than in 1,4-dimethoxybenzene only in the first assessment. Adding indole to 1,4-dimethoxybenzene did not improve beetle captures.O besouro Astylus variegatus (Germ. (Coleoptera: Melyridae é freqüentemente encontrado em flores onde se alimenta de pólen. Respostas de A. variegatus a atraentes voláteis florais foram estudadas em campos de feijão, Phaseolus vulgaris L. Armadilhas, originalmente desenvolvidas para capturar Diabrotica speciosa (Germ. (Coleoptera: Chrysomelidae, consistiram de garrafas plástica (2 L com 150 perfurações (5 mm de diâmetro pintadas com tinta amarelo ouro contendo no seu interior uma fita plástica (3,5 ´ 25,0 cm com pó seco de frutos de Lagenaria vulgaris (L. (0,28% de cucurbitacina B estimulante alimentar e arrestante para diabroticíneos pulverizados com inseticida carbaril. Os tratamentos foram: 1,4-dimetoxibenzeno (um ou dois liberadores por armadilha; 1,4-dimetoxibenzeno + indol; 1,4-dimetoxibenzeno + cinamaldeído e testemunha (sem volátil. As taxas de liberação dos semioquímicos (por 10 dias foram de aproximadamente 32 mg dia-1 por liberador em condições de laboratório. Armadilhas iscadas com 1,4-dimetoxibenzeno capturaram mais insetos que a testemunha, três e sete dias após instalação das armadilhas. Dez dias após o início dos experimentos, não foram verificadas diferenças entre os tratamentos, no número de besouros capturados. Capturas foram maiores no tratamento com 1,4-dimetoxibenzeno + cinamaldeído do que no 1,4-dimetoxibenzeno sozinho na primeira avaliação. Adição do indole ao 1,4-dimetoxibenzeno não aumentou as capturas.

  13. Attraction of Neomegalotomus parvus (Westwood)(Heteroptera: alydidae) to cow urine and ammonia Atração de Neomegalotomus parvus (Westwood) (Heteroptera: alydidae) por urina de vaca e amônia

    OpenAIRE

    Jovenil José da Silva; Iara Cintra de Arruda-Gatti; Adriana Yatie Mikami; Aline Pissinati; Antônio Ricardo Panizzi; Mauricio Ursi Ventura

    2010-01-01

    The alydid bug parvus (Westwood) is not easily detected in the field and the discovery of attractants may be a suitable way to monitor this species. The attraction of N. parvus to traps (transparent, transparent green and yellow) baited with cow urine and ammonia was studied in two field trials. Traps were placed near a terrace with pigeon pea plants (Cajanus cajan L.). Tap water, NaCl 10% aqueous solution (w/v), cow urine, and ammonia (NH4OH 1% aqueous solution) were tested as attractants in...

  14. RDH10 is the Primary Enzyme Responsible for the First Step of Embryonic Vitamin A Metabolism and Retinoic Acid Synthesis

    OpenAIRE

    Farjo, Krysten M.; Moiseyev, Gennadiy; Nikolaeva, Olga; Sandell, Lisa L.; Trainor, Paul A; Ma, Jian-xing

    2011-01-01

    Retinoic acid (atRA) signaling is essential for regulating embryonic development, and atRA levels must be tightly controlled in order to prevent congenital abnormalities and fetal death which can result from both excessive and insufficient atRA signaling. Cellular enzymes synthesize atRA from Vitamin A, which is obtained from dietary sources. Embryos express multiple enzymes that are biochemically capable of catalyzing the initial step of Vitamin A oxidation, but the precise contribution of t...

  15. Ethanol Effects On Physiological Retinoic Acid Levels

    OpenAIRE

    Napoli, Joseph L.

    2011-01-01

    All-trans-retinoic acid (atRA) serves essential functions during embryogenesis and throughout post-natal vertebrate life. Insufficient or excess atRA causes teratogenic and/or toxic effects in the developing embryo: interference with atRA biosynthesis or signaling likely underlies some forms of cancer. Many symptoms of vitamin A (atRA precursor) deficiency and/or toxicity overlap with those of another pleiotropic agent—ethanol. These overlapping symptoms have prompted research to understand w...

  16. Sweet’s syndrome during the treatment of acute promyelocytic leukemia with all-trans retinoic acid

    OpenAIRE

    Park, Chi Jun; Bae, Young Deok; Choi, Ji Yong; Heo, Pil Seog; Lee, Keun Seok; Park, Young Suk; Lee, Jung-Ae

    2001-01-01

    All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet’s syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet’s syndrome associated with ATRA ...

  17. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion

  18. All-Trans Retinoic Acid Inhibits Human Colorectal Cancer Cells RKO Migration via Downregulating Myosin Light Chain Kinase Expression through MAPK Signaling Pathway.

    Science.gov (United States)

    Zuo, Li; Yang, Xiaoping; Lu, Man; Hu, Ruolei; Zhu, Huaqing; Zhang, Sumei; Zhou, Qing; Chen, Feihu; Gui, Shuyu; Wang, Yuan

    2016-10-01

    All-trans-retinoic acid (ATRA) inhibits the invasive and metastatic potentials of various cancer cells. However, the underlying mechanism is unclear. Here, we demonstrate that ATRA inhibited colorectal cancer cells RKO (human colon adenocarcinoma cell) migration by downregulating cell movement and increasing cell adhesion. ATRA inhibited the expression and activation of myosin light chain kinase (MLCK) in RKO cells, while the expression level of MLC phosphatase (MLCP) had no change in RKO cells treated with or without ATRA. The expression and activity of MLC was also inhibited in RKO cells exposed to ATRA. Intriguingly, ATRA increased the expression of occludin messenger RNA (mRNA) and protein and its localization on cell membrane. However, ATRA did not change the expression of zonula occludens 1 (ZO-1), but increased the accumulation of ZO-1 on RKO cells membrane. ML-7, an inhibitor of MLCK, significantly inhibited RKO cell migration. Furthermore, knockdown of endogenous MLCK expression inhibited RKO migration. Mechanistically, we showed that MAPK-specific inhibitor PD98059 enhanced the inhibitory effect of ATRA on RKO migration. In contrast, phorbol 12-myristate 13-acetate (PMA) attenuated the effects of ATRA in RKO cells. Moreover, knocking down endogenous extracellular signal-regulated kinase (ERK) expression inhibited MLCK expression in the RKO cells. In conclusion, ATRA inhibits RKO migration by reducing MLCK expression via extracellular signal-regulated kinase 1/Mitogen-activated protein kinase (ERK1/MAPK) signaling pathway. PMID:27564600

  19. Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia.

    Science.gov (United States)

    Unal, Selma; Gümrük, Fatma; Cetin, Mualla; Hiçsönmez, Gönül

    2005-01-01

    All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.

  20. Apoptosis of Human Pancreatic Carcinoma Cells Induced By All-Trans Retinoic Acid and Interferon

    Institute of Scientific and Technical Information of China (English)

    Xiao-hua Wang; Yuan-qin Yin; Ping Ma; Cheng-guang Sui; Fan-dong Meng; Jiang You-hong

    2009-01-01

    Objective: To investigate the apoptosis of human pancreatic carcinoma PC3 cells induced by the combination of all-trans retinoic acid (ATRA) with interferon alpha (IFN-α). Methods: PC3 cells were treated with ATRA and IFN-α. The inhibitory rate of PC3 cell proliferation was detected using MTT method. Cellular apoptosis was determined with flow cytometry. The percentage of PC3 cell apoptosis was assayed using TUNEL methods. Results: ATRA and IFN-α could inhibit cellular proliferation and induces cellular apoptosis of PC3 cells. The inhibitory effect was stronger when the ATRA and IFN-α were combined as a therapy. Conclusion: ATRA inhibits the proliferation of PC3 cells and induce the apoptosis of PC3 cells. The combination of IFN-α with ATRA may enhance these effects on PC3 cells.

  1. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

  2. Pharmacogenomic analysis of retinoic-acid induced dyslipidemia in congenic rat model

    OpenAIRE

    Krupková, Michaela; Liška, František; Šedová, Lucie; Křenová, Drahomíra; Křen, Vladimír; Šeda, Ondřej

    2014-01-01

    Background All-trans retinoic acid (ATRA, tretinoin) is a vitamin A derivative commonly used in the treatment of diverse conditions ranging from cancer to acne. In a fraction of predisposed individuals, the administration of ATRA is accompanied by variety of adverse metabolic effects, particularly by the induction of hyperlipidemia. We have previously derived a minimal congenic SHR.PD-(D8Rat42-D8Arb23)/Cub (SHR-Lx) strain sensitive to ATRA-induced increase of triacylglycerols and cholesterol ...

  3. Effect of Retinoic Acid in a Mouse Model of Allergic Rhinitis

    OpenAIRE

    Son, Hye-Lim; Park, Hyang-Rim; Park, Yong-Jin; Kim, Soo-Whan

    2015-01-01

    Purpose All-trans retinoic acid (ATRA) modulates immune responses by affecting T cells. Several studies have revealed that allergic inflammation of the lower airways is negatively associated with the vitamin A concentration. However, the role of ATRA in allergic inflammation of the upper airways is unclear. We investigated the effects of ATRA in an allergic rhinitis mouse model. Methods BALB/c mice except control groups (CON group) were sensitized with and challenged intra-nasally with Dermat...

  4. PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations

    Science.gov (United States)

    Li, Yuan; Qi, Xian Rong; Maitani, Yoshie; Nagai, Tsuneji

    2009-02-01

    The purpose of this study was to characterize the properties in vitro, i.e. release, degradation, hemolytic potential and anticancer activity, and in vivo disposition of all-trans-retinoic acid (ATRA) in rats after administration of ATRA-loaded micelle-like nanoparticles. The amphiphilic block copolymers consisted of a micellar shell-forming mPEG block and a core-forming PLA block. The mPEG-PLA nanoparticles prepared by an acetone volatilization dialysis procedure were identified as having core-shell structure by 1H NMR spectroscopy. Critical association concentration, drug contents, loading efficiency, particle size and ξ potential were evaluated. The release of ATRA from the nanoparticles and the degradation of PLA were found to be mostly associated with the compositions of the nanoparticles. ATRA release was faster at smaller molecular weight of copolymer and lower drug contents. In vitro, the incorporation of ATRA in mPEG-PLA nanoparticles reduced the hemolytic potential of ATRA. Furthermore, anticancer activity of ATRA against HepG2 cell was increased by encapsulation, which showed an enhancement of tumor treatment of ATRA. In vivo, after intravenous injection to rats, the levels of ATRA in the blood stream and the bioavailability were higher for ATRA-loaded mPEG-PLA nanoparticles than those for ATRA solution. In conclusion, the structure of the mPEG-PLA diblock copolymer could be modulated to fit the demand of in vitro and in vivo characterizations of nanoparticles. The mPEG-PLA nanoparticles' loading ATRA have a promising future for injection administration.

  5. Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

    OpenAIRE

    Kwon, Oh Sang; Pyo, Hyun Keol; Oh, Youn Jin; Han, Ji Hyun; Lee, Se Rah; Chung, Jin Ho; Eun, Hee Chul; Kim, Kyu Han

    2007-01-01

    Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal...

  6. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    Science.gov (United States)

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.—Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. PMID:19890016

  7. Scrotal ulceration following all-trans retinoic acid therapy for acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Illias Tazi

    2011-01-01

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in most cases of acute promyelocytic leukemia. Toxicity of ATRA has been shown to be mild, consisting of headache, dry skin, dermatitis, and gastrointestinal disorders. We describe a case of scrotal ulceration with ATRA use in a Moroccan patient, an occurrence that has been rarely reported in the medical literature. The pathogenesis of scrotal ulceration remains unknown. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  8. Effect of differents baits as attractant for blowflies (diptera at Valonguinho, Universidade Federal Fluminense, Niterói, RJ, Brazil Efeito de diferentes iscas na atração de califorídeos (diptera no campus do Valonguinho, Universidade Federal Fluminense, Niterói, RJ, Brasil

    Directory of Open Access Journals (Sweden)

    José M. D'almeida

    2007-12-01

    Full Text Available It was carried out a survey of blowflies in a área of the Campus (Valonguinho of the Universidade Federal Fluminense, Niterói, Rio de Janeiro. The collections were performed with traps, using baits of fish (sardine, bovine liver, shrimps and banana. Were collected 6015 flies, Chrysomya megacephala and Lucilia eximia were the most frequent (50.55% and 21.52%, respectively. The flies were more abundant in February and March and the most attractive bait was fish (38.32%.Foi realizado um estudo sobre califorideos no Campus do Valonguinho, Universidade Federal Fluminense. A pesquisa foi efetuada de dezembro de 2003 a novembro de 2004, com coletas feitas com armadilhas utilizando iscas à base de peixe (sardinha, fígado bovino, camarão e banana. Foram coletados 6015 califorideos, Chrysomya megacephala e Lucilia eximia foram as mais freqüentes (50,55% e 21, 52%, respectivamente. A isca mais atrativa foi peixe (38,32% com picos populacionais em fevereiro e março.

  9. Population structure, growth and production of a recent brachiopod from the Chilean fjord region

    KAUST Repository

    Baumgarten, Sebastian

    2013-12-04

    Magellania venosa, the largest recent brachiopod, occurs in clusters and banks in population densities of up to 416 ind m-2 in Comau Fjord, Northern Chilean fjord region. Below 15 m, it co-occurs with the mytilid Aulacomya atra and it dominates the benthic community below 20 m. To determine the question of why M. venosa is a successful competitor, the in situ growth rate of the brachiopod was studied and its overall growth performance compared with that of other brachiopods and mussels. The growth in length was measured between February 2011 and March 2012 after mechanical tagging and calcein staining. Settlement and juvenile growth were determined from recruitment tiles installed in 2009 and from subsequent photocensus. Growth of M. venosa is best described by the general von Bertalanffy growth function, with a maximum shell length (L∞) of 71.53 mm and a Brody growth constant (K) of 0.336 year-1. The overall growth performance (OGP index = 5.1) is the highest recorded for a rynchonelliform brachiopod and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM ind-1 year-1 at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM year-1 m-2 (1-57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass of the population (P/B--ratio) is low (0.535) and M. venosa may play only a minor role in the food chain. Settling dynamics indicates that M. venosa is a pioneer species with low juvenile mortality. The coexistence of the brachiopod and bivalve suggests that brachiopod survival is affected by neither the presence of potential brachiopod predators nor that of space competitors (i.e. mytilids).

  10. The Effects of Quercetin and Retinoic acid on Skeletal System of Rat Embryos in Prenatal Period

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    Nahid Gohari-Behbahani

    2014-12-01

    Full Text Available Background: Prenatal rat embryo exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-trans-retinoic acid (atRA. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of atRA was evaluated. Materials and Methods: In this experimental study, 40 pregnant rats were divided into 7 groups. Control group received normal saline and test groups received dimethylsulfoxide (DMSO, quercetin (75 mg/kg, quercetin (200 mg/kg, atRA (25 mg/kg, atRA (25 mg/kg plus quercetin (75 mg/kg and atRA (25 mg/kg plus quercetin (200 mg/kg, intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Results: Cleft palate, exencephaly and spina bifida incidence were 30.76%, 61.53% and 30.76% range in group which received only atRA. Cleft palate, exencephaly and spina bifida incidence were 11.11%, 16.66% and 5.55% in group which received atRA plus quercetin (75 mg/kg. However, cleft palate, exencephaly and spina bifida incidence were 10.52%, 10.52% and 0% in group which received atRA plus quercetin (200 mg/kg. The means of weight and length of fetuses from rat that received atRA plus quercetin (75 mg/kg were significantly greater than those received only atRA. Conclusion: It is concluded that quercetin decreased teratogenicity induced by atRA, but this subject needs more detailed evaluation.

  11. All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats.

    Science.gov (United States)

    Zhang, Chao; Kong, Xiaohong; Ning, Guangzhi; Liang, Zhipin; Qu, Tongjun; Chen, Feiran; Cao, Daigui; Wang, Tianyi; Sharma, Hari S; Feng, Shiqing

    2014-04-01

    Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRA's ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.

  12. Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Jin Man Kim; Sang Wook Kang; Su-Mi Shin; Duck Su Kim; Kyong-Kyu Choi; Eun-Cheol Kim; Sun-Young Kim

    2014-01-01

    All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol?L21 ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.

  13. In vitro induction and differentiation of umbilical cord mesenchymal stem cells into neuron-like cells by alltrans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Wei; Jin; Yao-Peng; Xu; An-Huai; Yang; Yi-Qiao; Xing

    2015-01-01

    AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) into neuron-like cells, although it is understood that all-trans retinoic acid(ATRA) regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis.METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured h UC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry.RESULTS: The data showed that low concentrations of ATRA(0.5 μmol, 0.25 μmol) had no effect on the number of cells. However, treatment with 1.0 μmol or 2.0 μmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 μmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24 h. We further showed that 0.5 μmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells.CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of h UC-MSCs. These findings have implications on the use of ATRA-differentiated h UC-MSCs for the study of neural degeneration diseases.

  14. Catalase Induced by All-Trans Retinoic Acid Is Involved in Antiproliferation of 36B10 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2010-11-15

    All-trans retinoic acid (ATRA) has antiproliferative effects against brain tumor cells. Recently, ATRA has been reported to induce catalase. We investigated whether catalase induction by ATRA is associated with its antiproliferative effects. 36B10 cells were exposed to 0-50{mu}M ATRA for 24 or 48 hours and mRNA, protein, and activity of catalase were measured. Reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescin diacetate. A clonogenic assay was used to confirm the cytotoxic effect. The mRNA, protein, and activity of catalase were found to increase in a concentration- and incubation- time-dependent manner. The increase in catalase activity induced by ATRA was decreased by the addition of 3-amino-1,2,4-triazole (ATZ). ROS was also increased with ATRA and decreased by the addition of ATZ. The decrease in cell survival induced by ATRA was partly rescued by ATZ. Catalase induction by ATRA is involved in ROS overproduction and thus inhibits the proliferation of 36B10 cells.

  15. All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia : a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies

    NARCIS (Netherlands)

    Sanz, Miguel A.; Montesinos, Pau; Kim, Haesook T.; Ruiz-Argueelles, Guillermo J.; Undurraga, Maria S.; Uriarte, Maria R.; Martinez, Lem; Jacomo, Rafael H.; Gutierrez-Aguirre, Homero; Melo, Raul A. M.; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M.; Vellenga, Edo; Holowiecka, Alexandra; Gonzalez-Huerta, Ana J.; Fernandez, Pascual; De la Serna, Javier; Brunet, Salut; De Lisa, Elena; Gonzalez-Campos, Jose; Ribera, Jose M.; Krsnik, Isabel; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C.; Lo-Coco, Francesco; Lowenberg, Bob; Rego, Eduardo M.

    2015-01-01

    Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diag

  16. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui;

    2013-01-01

    While all-trans retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) has been the paradigm of targeted therapy for oncogenic transcription factors, the underlying mechanisms remain largely unknown, and a significant number of patients still relapse and become ATRA resistant. We...

  17. Acute effects of all-trans-retinoic acid in ischemic injury

    Science.gov (United States)

    All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. We investigated the relatively acute effects of ATRA (100 nM and 1 µM) on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelli...

  18. The Achilles tendon resting angle as an indirect measure of Achilles tendon length following rupture, repair, and rehabilitation

    Directory of Open Access Journals (Sweden)

    Michael R. Carmont

    2015-04-01

    Conclusion: The ATRA increases following injury, is reduced by surgery, and then increases again during initial rehabilitation. The angle also correlates with patient-reported symptoms early in the rehabilitation phase and with heel-rise height after 1 year. The ATRA might be considered a simple and effective means to evaluate Achilles tendon function 1 year after the rupture.

  19. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    Science.gov (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  20. EXPERIMENTAL STUDY OF THE DIFFERENTIATION HPV16 SUBGENES-IMMORTALIZED HUMAN ENDOCERVICAL CELLS INDUCED BY ALL-TRANS-RETINOIC ACID

    Institute of Scientific and Technical Information of China (English)

    LI Yi-ming; ZHAO Yong; LIN Xiao

    2005-01-01

    Objective: To investigate the differentiation-inducing effects of all-trans-retinoic (ATRA) to HPV16 subgenesimmortalized human endocervical cells (H8 cell) in vitro. Methods: HPV16 subgenes-immortalized human endocervical cells(H8 cells) were cultured in vitro. After treated with ATRA, the proliferation of immortalized human endocervical cells was measured by MTT assay; morphological changes were observed using M and TEM; cell cycle was analyzed by FCM;expression of Ki67 was tested using immunocytochemistry and the activity of telomerase was tested using PCR-ELISA.Results: ATRA could inhibit proliferation of H8 cells significantly and induce their morphodifferentiation. According to FCM, H8 cells accumulated in G1 phase and expression of Ki67 and activity of telomerase reduced significantly after treatment with ATRA. Conclusion: ATRA could induce the differentiation of H8 cell line obviously, which might be achieved by inhibiting proliferation, blocking cell cycle, and reducing activity of telomerase.

  1. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2016-01-01

    Full Text Available Background. Acute promyelocytic leukemia is characterized by t(15;17. This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA, a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

  2. Eosinophils from Murine Lamina Propria Induce Differentiation of Naive T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

    Directory of Open Access Journals (Sweden)

    Hong-Hu Chen

    Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

  3. The effect pathway of retinoic acid through regulation of retinoic acid receptor in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Qiao Wu; Zheng-Ming Chen; Wen-Jin Su

    2001-01-01

    AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.``

  4. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  5. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta

    Science.gov (United States)

    Huo, Lijun; Cui, Dongmei; Yang, Xiao; Gao, Zhenya; Trier, Klaus

    2013-01-01

    Purpose All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. Methods HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 μmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence. Results After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARβ), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK. Conclusions ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta. PMID:23946634

  6. Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    LU Tai-ying; LI Wen-cai; CHEN Ren-yin; FAN Qing-xia; WANG Liu-xing; WANG Rui-lin; LU Shi-xin; MENG Hui

    2011-01-01

    Background The potential application of retinoic acid receptor activators,such as all trans-retinoic acid (ATRA),for treating various cancers have been studied both pre-clinically and clinically.Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown.We have explored the anticancer effect of ATRA in ESCC,and in this study,the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line,EC9706,in nude mice.Methods The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice.Reverse transcription-polymerase chain reaction (RT-PCR),Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.Results Compared to the control group,the tumor inhibition rates in the low dose ATRA,high dose ATRA,and 5-FU groups were 83.21%,88.32%,91.02%,respectively.The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P <0.05).The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31,CD34,and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P <0.05).Conclusions ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice.These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction,which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.

  7. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

    Science.gov (United States)

    Campione, Elena; Gaziano, Roberta; Marino, Daniele; Orlandi, Augusto

    2016-01-01

    Purpose Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. PMID:27199548

  8. Effect of all-trans retinoic acid 0n drug sensitivity and expression of survivin in LoVo cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background All-trans retinoic acid(ATRA)can influence the tumor cell proliferation cycle,and some chemotherapeutic drugs are cycle specific.In this study,we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells.Methods The cell cycle of LoVo cells was evaluated using flow cytometry(FCM).Cell viability was analyzed using the MTT assay.The morphologic changes in the treated LoVo cells were measured with acridine orange (AO)/ethidium bromide(EB)staining.Expression of survivin in LoVo cells was analyzed by immunofluorescence assay.Results After LoVo cells were treated with ATRA,the G0/G1 ratio of the tumor cells increased and the cell ratio of Sand G2/M-phase decreased.Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil(5-FU)or mitomycin c(MMC) and was evaluated by fluorescence microscopy.Expression level of survivin in the tumor cells decreased after ATRA combination treatment.Conclusions ATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells.The combination of ATRA and 5-FU or MMC promoted cell apoptosis,and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.

  9. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Li Xiang-Xin

    2014-01-01

    Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

  10. Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor.

    Directory of Open Access Journals (Sweden)

    Aurore Gely-Pernot

    2015-10-01

    Full Text Available All-trans retinoic acid (ATRA is instrumental to male germ cell differentiation, but its mechanism of action remains elusive. To address this question, we have analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors (RXRA, RXRB and RXRG or all ATRA receptors (RARA, RARB and RARG. We demonstrate that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the set of defects observed both upon ablation of RAR in spermatogonia. We also show that ATRA activates RAR and RXR bound to a conserved regulatory region to increase expression of the SALL4A transcription factor in spermatogonia. Our results reveal that this major pluripotency gene is a target of ATRA signaling and that RAR/RXR heterodimers are the functional units driving its expression in spermatogonia. They add to the mechanisms through which ATRA promote expression of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia differentiation. Importantly, they indicate also that meiosis eventually occurs in the absence of a RAR/RXR pathway within germ cells and suggest that instructing this process is either ATRA-independent or requires an ATRA signal originating from Sertoli cells.

  11. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yun; Shen, Shao-Ming; Zhang, Fei-Fei; Wu, Zhao-Xia; Han, Bin [Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn [Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer ANP32B inhibited ATRA activated transcriptional activity of RAR{alpha}. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RAR{alpha}). These data will shed new insights into understanding the biological functions of ANP32B protein.

  12. Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2005-10-28

    Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma (IFNgamma) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNgamma induced a faster, higher, and more stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNgamma than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNgamma receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARalpha ligand, regulates IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling pathway, from the plasma membrane to the nuclear transcription factors.

  13. Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chen Wantao

    2008-06-01

    Full Text Available Abstract Background Antisense oligonucleotides against hTR (As-ODN-hTR have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo. Methods In situ human oral squamous cell carcinoma (OSCC models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined. Results Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues. Conclusion The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.

  14. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein

    Directory of Open Access Journals (Sweden)

    Taguchi Takahiro

    2010-12-01

    Full Text Available Abstract Background Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor (GIST patients. Unfortunately, most patients responding to imatinib will eventually exhibit imatinib-resistance, the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid (ATRA on GIST cell lines. Methods Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT, its downstream proteins, and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham. Results and conclusion In this work, for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells, rounded-up cells, and activated the caspase-3 protein. In further examination, we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover, ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal, AKT activity, but not MAPK activity. We also have demonstrated that combination of ATRA with imatinib showed additive effect by isobologram, suggesting that the combination of ATRA and imatinib may be a novel potential therapeutic option for GIST treatment. Furthermore, the scracht assay result suggested that ATRA was a potential reagent to prevent the invasion or metastasis of GIST cells.

  15. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes.

    Science.gov (United States)

    Song, Xiuzu; Xu, Aie; Pan, Wei; Wallin, Brittany; Kivlin, Rebecca; Lu, Shan; Cao, Cong; Bi, Zhigang; Wan, Yinsheng

    2008-08-01

    The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

  16. Study of the synergistic effects of all-transretinoic acid and C-phycocyanin on the growth and apoptosis of A549 cells.

    Science.gov (United States)

    Li, Bing; Gao, Mei-Hua; Lv, Cong-Yi; Yang, Peng; Yin, Qi-Feng

    2016-03-01

    In the present study, we investigated the effects of the combination of all-transretinoic acid (ATRA) and natural nontoxic C-phycocyanin (C-PC) on the growth of A549 lung cancer cells in vitro and in vivo. Furthermore, the anticancer mechanism of the drug combination was revealed. Results showed both C-PC and ATRA could inhibit the growth of A549 cells in vivo. The combination of ATRA+C-PC could yield a higher inhibition rate. C-PC exerted a major effect on the proliferation of human embryo lung cells, but ATRA at a high concentration exerted an inhibitory effect. In addition, ATRA+C-PC could decrease the CDK4 mRNA level, but upregulated caspase-3 protein expression and induced cell apoptosis. A mouse model with tumor was constructed by a subcutaneous injection to the left axilla of nu nude (NU/NU) mice. Compared with the control group, the tumor weight was decreased in the single-drug treatment group and was the lowest in the combination group. C-PC+ATRA could upregulate tumor necrosis factor levels and downregulate Bcl-2 expression and the cyclin D1 gene in the tumor. C-PC could promote T cells' activities and spleen weight, but a single use of ATRA exerted an opposite effect. The dosage of ATRA could be reduced when combined with C-PC to reduce the toxic side-effects. In summary, the antitumor effects of the C-PC+ATRA combination were more significant than a single drug in vivo and in vitro. PMID:25812039

  17. The effects of PAHs and N-PAHs on retinoid signaling and Oct-4 expression in vitro.

    Science.gov (United States)

    Beníšek, Martin; Kubincová, Petra; Bláha, Luděk; Hilscherová, Klára

    2011-02-01

    Polycyclic aromatic hydrocarbons (PAHs) and their N-heterocyclic analogs (N-PAHs) are important environmental contaminants with negative effects in living organisms, including teratogenicity and embryotoxicity. Though most studies linked their embryotoxicity with aryl hydrocarbon receptor (AhR) and cytochrome P450 activation, the exact mechanism is not known. Other mechanisms such as disruption of retinoid signaling were recently suggested to be of importance. This study investigated PAHs and N-PAHs interference with retinoid signaling in vitro by modulating all-trans retinoic acid (ATRA) mediated response in a reporter gene assay using P19/A15 cell line. Further, effects on pluripotency and differentiation processes were evaluated by measuring octamer-4 (Oct-4), an important pluripotency marker and master differentiation factor. Two of the studied compounds, benz[a]anthracene and benz[c]acridine significantly up-regulated ATRA-mediated response in the co-exposure with a range of ATRA concentrations. Another structural N-PAH variant, 1,7-phenanthroline, downregulated ATRA-mediated response at most of tested ATRA concentrations and exposure times. Interesting concentration-dependent biphasic effects (i.e. downregulation with subsequent up-regulation to control levels) were observed at co-exposures of ATRA and parent PAH phenanthrene. Non significant Oct-4 modulation in co-exposure with ATRA was observed at compounds, which potentiated ATRA-mediated effects in the reporter gene assay. On the other hand, 1,7-phenanthroline and phenanthrene significantly suppressed Oct-4 levels in higher tested concentrations. Our results further extend the knowledge of PAH and N-PAH in vitro effects and indicate that these environmental toxicants may have influence on differentiation process and embryonic development by interfering with ATRA signaling and by modulating levels of Oct-4. PMID:21111795

  18. RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

    Institute of Scientific and Technical Information of China (English)

    Lei Guo; Yu-yan Zhao; Shi-liang Zhang; Kui Liu; Xiao-yu Gao

    2008-01-01

    Objective To evaluate the effects of retinoic acid (RA) on expression of bone morphogenetic protein 7 (BMP-7)in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA (ATRA) was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expres-sion in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein ex-pressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA (45.5%) was significantly higher than 50 mg/kg ATRA (12.5%, P<0.05). BMP-7 mRNA expression de-creased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mR.NA and protein levels in MC-3T3-E1cells treated with 1 × 10-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated ceils (P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.

  19. Characterization and performance of short cationic antimicrobial peptide isomers.

    Science.gov (United States)

    Juba, Melanie; Porter, Devin; Dean, Scott; Gillmor, Susan; Bishop, Barney

    2013-07-01

    Cationic antimicrobial peptides (CAMPs) represent an ancient defense mechanism against invading bacteria, with peptides such as the cathelicidins being essential elements of vertebrate innate immunity. CAMPs are typically associated with broad-spectrum antimicrobial potency and limited bacterial resistance. The cathelicidin identified from the elapid snake Naja atra (NA-CATH) contains a semi-conserved repeated 11-residue motif (ATRA motif) with a sequence pattern consistent with formation of an amphipathic helical conformation. Short peptide amides (ATRA-1, -1A, -1P, and -2) generated based on the pair of ATRA motifs in NA-CATH exhibited varied antimicrobial potencies. The small size of the ATRA peptides, coupled with their varied antimicrobial performances, make them interesting models to study the impact various physico-chemical properties have on antimicrobial performance in helical CAMPs. Accordingly, the D- and L-enantiomers of the peptide ATRA-1A, which in earlier studies had shown both good antimicrobial performance and strong helical character, were investigated in order to assess the impact peptide stereochemistry has on antimicrobial performance and interaction with chiral membranes. The ATRA-1A isomers exhibit varied potencies against four bacterial strains, and their conformational properties in the presence of mixed zwitterionic/anionic liposomes are influenced by anionic lipid content. These studies reveal subtle differences in the properties of the peptide isomers. Differences are also seen in the abilities of the ATRA-1A isomers to induce liposome fusion/aggregation, bilayer rearrangement and lysing through turbidity studies and fluorescence microscopy. The similarities and differences in the properties of the ATRA-1A isomers could aid in efforts to develop D-peptide-based therapeutics using high-performing L-peptides as templates.

  20. Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid

    OpenAIRE

    White, Jeffrey C.; Shankar, V. Narayanaswamy; Highland, Margaret; Epstein, Miles L; DeLuca, Hector F.; Clagett-Dame, Margaret

    1998-01-01

    Vitamin A is required for reproduction and normal embryonic development. We have determined that all-trans-retinoic acid (atRA) can support development of the mammalian embryo to parturition in vitamin A-deficient (VAD) rats. At embryonic day (E) 0.5, VAD dams were fed purified diets containing either 12 μg of atRA per g of diet (230 μg per rat per day) or 250 μg of atRA per g of diet (4.5 mg per rat per day) or were fed the purified diet supplemented with a source of retinol (100 units of re...

  1. Synergistic effect of all-trans-retinoic acid and arsenic trioxide on growth inhibition and apoptosis in human hepatoma, breast cancer, and lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Le-Min Lin; Bao-Xin Li; Jian-Bing Xiao; Dan-Hua Lin; Bao-Feng Yang

    2005-01-01

    AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As2O3)-induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors.METHODS: Human hepatoma cell lines HepG2, Hep3B,human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As2O3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis were measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH)and glutathione-S-transferase (GST) activities were determined using commercial kits.RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1,and 10 μmol/L) could synergistically potentiate As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As2O3 or As2O3+ATRA, while AGZY-83-a with higher GSH or GST activities was less sensitive to As2O3or As2O3+ATRA. Treatment with 2 μmol/L As2O3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 μmol/L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As2O3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As2O3 and ATRA for 72 h as compared to As2O3 alone.CONCLUSION: ATRA can strongly potentiate As2O3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As2O3 or As2O3+ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergistically potentiates As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis.

  2. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Directory of Open Access Journals (Sweden)

    Mohammed Al Huneini

    2013-05-01

    Full Text Available We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA for the treatment of acute promyelocytic leukemia (APL. Between October 2007 and March 2010, three males and one female (age range 19-35 years were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

  3. Treatment of an acute promyelocytic leukemia relapse using arsenic trioxide and all-trans-retinoic in a 6-year-old child.

    Science.gov (United States)

    Rock, Nathalie; Mattiello, V; Judas, C; Huezo-Diaz, P; Bourquin, J P; Gumy-Pause, F; Ansari, M

    2014-03-01

    In adult therapy, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are recognized as active treatment of relapsed acute promyelocytic leukemia (APL). The efficacy of this combination in pediatric APL has not yet been well established. We report the case of a 6-year-old girl with relapsed APL, with a PML-RARα mutation, treated with a combination of ATO and ATRA. Over a period of 5 months, she received in total, 75 doses of intravenous ATO and 40 doses of oral ATRA. Currently, 22 months after relapse, she is still in complete remission. Here, we describe treatment of a relapsed APL in a child with limited treatment of ATO and ATRA and review the literature. PMID:24498972

  4. MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy.

    Science.gov (United States)

    Aslam, Muhammad N; McClintock, Shannon; Khan, Shazli P; Perone, Patricia; Allen, Ronald; Ouillette, Peter D; Dame, Michael K; Cheng, Jason X; Kunkel, Steven L; Varani, James

    2015-08-01

    MDI 301 is a novel 9-cis retinoic acid derivative in which the terminal carboxylic acid group has been replaced by a picolinate ester. MDI 301, a retinoic acid receptor-α - agonist, suppressed the growth of several human myeloid leukemia cell lines (HL60, NB4, OCI-M2, and K562) in vitro and induced cell-substrate adhesion in conjunction with upregulation of CD11b. Tumor growth in HL60-injected athymic nude mice was reduced. In vitro, MDI 301 was comparable to all-trans retinoic acid (ATRA) whereas in vivo, MDI 301 was slightly more efficacious than ATRA. Most importantly, unlike what was found with ATRA treatment, MDI 301 did not induce a cytokine response in the treated animals and the severe inflammatory changes and systemic toxicity seen with ATRA did not occur. A retinoid with these characteristics might be valuable in the treatment of promyelocytic leukemia, or, perhaps, other forms of myeloid leukemia. PMID:26010252

  5. Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression

    Science.gov (United States)

    The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive propertiesofatRAwhichfunctionstoregulate levels ofcellcycleproteinsessentialfortheGliS transition...

  6. Plaat

    Index Scriptorium Estoniae

    2008-01-01

    Laseringi kauplustes müügilolevatest heliplaatidest: Bizarre "Cafe De Flor", Hocico "Memorias Atras", Portishead "Third", Alanis Morissette "Flavors Of Entanglement", Radiohead "The Best Of", Kelder "Vikerkaar ja latimeeria"

  7. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    Directory of Open Access Journals (Sweden)

    Navneet Gill

    2013-01-01

    Conclusion: From above findings, it can be concluded that ATRA exerts anti-inflammatory and anti-hyperalgesic effect, possibly through activation of PPAR-β/δ and subsequent reduction of oxido-nitrosative stress.

  8. FAQ about Recreational Therapy/Therapeutic Recreation

    Science.gov (United States)

    ... is the relationship between recreational therapy and therapeutic recreation? Therapeutic Recreation is the field ​​Recreational ... for individuals with disabilities." About the American Therapeutic Recreation Association: The American Therapeutic Recreation Association (ATRA) is ...

  9. Protein phosphatase 2A associates with Rb2/p130 and mediates retinoic acid-induced growth suppression of ovarian carcinoma cells

    DEFF Research Database (Denmark)

    Vuocolo, Scott; Purev, Enkhtsetseg; Zhang, Dongmei;

    2003-01-01

    Levels of Rb2/p130 protein are increased 5-10-fold following all-trans-retinoic acid (ATRA) treatment of the retinoid-sensitive ovarian adenocarcinoma cell line CAOV3, but not the retinoid-resistant adenocarcinoma cell line SKOV3. We found that this increase in Rb2/p130 protein levels in ATRA......-treated CAOV3 cells was the result of an increased protein stability. Moreover, Rb2/p130 exhibited a decreased ubiquitination following ATRA treatment. Because phosphorylation frequently mediates ubiquitination of proteins, we examined the serine/threonine phosphatase activity in our CAOV3 cells following ATRA...... treatment. A significant increase in Ser/Thr phosphatase activity was found, which correlated with a rise in the level of protein phosphatase 2A (PP2A) catalytic subunit-alpha. In addition, co-immunoprecipitation and glutathione S-transferase pull-down studies demonstrated that PP2A and Rb2/p130 associate...

  10. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  11. Budgetary impact of treating acute promyelocytic leukemia patients with first-line arsenic trioxide and retinoic acid from an Italian payer perspective.

    Directory of Open Access Journals (Sweden)

    Morgan Kruse

    Full Text Available The objective of this study was to estimate the net cost of arsenic trioxide (ATO added to all-trans retinoic acid (ATRA compared to ATRA plus chemotherapy when used in first-line acute promyelocytic leukemia (APL treatment for low to intermediate risk patients from the perspective of the overall Italian healthcare systemA Markov model was developed with 3 health states: stable disease, disease event and death. Each month, patients could move from stable to disease event or die from either state. After a disease event, patients discontinued initial treatment and switched to the other regimen as second-line therapy. Treatment regimens, efficacy and adverse events were derived from published sources and expert opinion; unit costs were collected from standard Italian sources. Clinical outcomes and costs for pre-ATO and post-ATO scenarios were combined with population and product utilization information to calculate the total budgetary impact using a 3-year time horizon; one-way sensitivity analyses were conducted. Three-year cumulative pharmacy costs for ATO+ATRA were €46,700 per-patient versus €6,500 for ATRA+chemotherapy; however, medical costs for ATO+ATRA were €12,300 per-patient versus €30,200 for ATRA+chemotherapy. The total budgetary impact was estimated to be an additional €127,300, €312,500 and €477,800 in the first, second and third years, respectively. The model was most sensitive to changes in the cost of the ATO+ATRA regimen during the consolidation phase. Budgetary impact models are valuable to payers making formulary decisions regarding the access and affordability of new medicines. The cost of treatment analysis showed that pharmacy costs for ATO+ATRA were higher than for ATRA+chemotherapy, while all other evaluated costs were lower for ATO+ATRA treated patients. The average budgetary impact was €305,900 per year overall, representing a 3.5% increase. Further research is needed to determine the cost-effectiveness of

  12. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins

    OpenAIRE

    Ying-Jung Chen; Chia-Yu Tsai; Wan-Ping Hu; Long-Sen Chang

    2016-01-01

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electr...

  13. Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions.

    Science.gov (United States)

    Lu, Ling; Lan, Qin; Li, Zhiyuan; Zhou, Xiaohui; Gu, Jian; Li, Qiang; Wang, Julie; Chen, Maogen; Liu, Ya; Shen, Yi; Brand, David D; Ryffel, Bernhard; Horwitz, David A; Quismorio, Francisco P; Liu, Zhongmin; Li, Bin; Olsen, Nancy J; Zheng, Song Guo

    2014-08-19

    Recent studies have demonstrated that thymus-derived naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize atRA stabilizes human natural Tregs (nTregs) under inflammatory conditions. atRA prevents human nTregs from converting to Th1 and/or Th17 cells and sustains their Foxp3 expression and suppressive function in vitro or in vivo following encounters with IL-1 and IL-6. Interestingly, adoptive transfer of human nTregs pretreated with atRA significantly enhanced their suppressive effects on xenograft-vs.-host diseases (xGVHDs), and atRA- but not rapamycin-pretreated nTregs sustained the functional activity against xGVHD after stimulation with IL-1/IL-6. atRA suppresses IL-1 receptor (IL-1R) up-regulation, accelerates IL-6R down-regulation, and diminishes their signaling events as well as prevents the up-regulation of STIP1 homology and U-Box containing protein 1 on Foxp3(+) cells following IL-1/IL-6 stimulation. atRA also increases histone acetylation on Foxp3 gene promoter and CpG demethylation in the region of Foxp3 locus (i.e., Treg-specific demethylated region). These results strongly implicate that nTregs primed with atRA may represent a novel treatment strategy to control established chronic immune-mediated autoimmune and inflammatory diseases. PMID:25099355

  14. All-Trans Retinoic Acid Induces DU145 Cell Cycle Arrest through Cdk5 Activation

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    Eugene Lin

    2014-05-01

    Full Text Available Background/Aims: All-trans retinoic acid (ATRA, the active form of vitamin A, plays an important role in the growth arrest of numerous types of cancer cells. It has been indicated that cyclin-dependent kinase 5 (Cdk5 activity can be affected by ATRA treatment. Our previous results demonstrate the involvement of Cdk5 in the fate of prostate cancer cells. The purpose of this study is to examine whether Cdk5 is involved in ATRA-induced growth arrest of the castration-resistant cancer cell line DU145 through up-regulating Cdk inhibitor protein, p27. Methods: DU145 cells were treated with ATRA, and cell proliferation, protein expression, and protein localization of Cdk5/p27 were examined. Cell proliferation and cell cycle distribution were also determined under Cdk5 inhibition induced by inhibitor or knockdown. Results: ATRA treatment inhibited DU145 cell proliferation and significantly increased p27 expression through Cdk5 up-regulation. Immunocytochemical data showed that a Cdk5 inhibitor reduced ATRA-triggered nuclear distribution of p27 in DU145 cells. The proliferation inhibition and G1 phase accumulation of DU145 cells were significantly increased by ATRA treatment, whereas Cdk5 inhibitor and siRNA could reverse these effects. Conclusions: Our results demonstrate that ATRA induced growth inhibition in castration-resistant prostate cancer cells through activating Cdk5 and p27. We hope this finding will increase the knowledge of prostate cancer treatment and can be applied in patients' nutritional control in the future.

  15. All-trans retinoic acid impairs the vasculogenic mimicry formation ability of U87 stem-like cells through promoting differentiation

    OpenAIRE

    LING, GENG-QIANG; LIU, YI-JING; Ke, Yi-Quan; Chen, Lei; JIANG, XIAO-DAN; JIANG, CHUAN-LU; Ye, Wei

    2015-01-01

    The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was previously reported to be promoted by cancer stem-like cells (SLCs). All-trans retinoic acid (ATRA), a potent reagent which drives differentiation, was reported to be able to eradicate cancer SLCs in certain malignancies. The aim of the present study was to investigate the effects of ATRA on the VM formation ability of U87 glioblastoma SL...

  16. Genetic and pathologic aspects of retinoic acid-induced limb malformations in the mouse

    OpenAIRE

    Lee, Grace S.; Liao, Xiaoyan; Shimizu, Hirohito; Collins, Michael D.

    2010-01-01

    Because all-trans retinoic acid (atRA) is teratogenic in all species tested and many of the specific defects induced are common across the phylogenetic spectrum, it would be logical to predict that murine strain differences in teratology to this agent are minimal. However, for specific defects, strain susceptibilities are vastly different. Studies with atRA have shown stark differences between C57BL/6 and SWV mouse strains in susceptibility to postaxial forelimb ectrodactyly and ectopic hindl...

  17. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta

    OpenAIRE

    Huo, Lijun; Cui, Dongmei; Yang, Xiao; Gao, Zhenya; Trier, Klaus; Zeng, Junwen

    2013-01-01

    Purpose All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. Methods HSFs w...

  18. All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

    International Nuclear Information System (INIS)

    NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

  19. Genital ulcers during treatment with ALL-trans retinoic acid for acute promyelocytic leukemia.

    Science.gov (United States)

    Fukuno, Kenji; Tsurumi, Hisashi; Goto, Hideko; Oyama, Masami; Tanabashi, Shinobu; Moriwaki, Hisataka

    2003-11-01

    Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  20. In Situ Catalyst Modification in Atom Transfer Radical Reactions with Ruthenium Benzylidene Complexes.

    Science.gov (United States)

    Lee, Juneyoung; Grandner, Jessica M; Engle, Keary M; Houk, K N; Grubbs, Robert H

    2016-06-01

    Ruthenium benzylidene complexes are well-known as olefin metathesis catalysts. Several reports have demonstrated the ability of these catalysts to also facilitate atom transfer radical (ATR) reactions, such as atom transfer radical addition (ATRA) and atom transfer radical polymerization (ATRP). However, while the mechanism of olefin metathesis with ruthenium benzylidenes has been well-studied, the mechanism by which ruthenium benzylidenes promote ATR reactions remains unknown. To probe this question, we have analyzed seven different ruthenium benzylidene complexes for ATR reactivity. Kinetic studies by (1)H NMR revealed that ruthenium benzylidene complexes are rapidly converted into new ATRA-active, metathesis-inactive species under typical ATRA conditions. When ruthenium benzylidene complexes were activated prior to substrate addition, the resulting activated species exhibited enhanced kinetic reactivity in ATRA with no significant difference in overall product yield compared to the original complexes. Even at low temperature, where the original intact complexes did not catalyze the reaction, preactivated catalysts successfully reacted. Only the ruthenium benzylidene complexes that could be rapidly transformed into ATRA-active species could successfully catalyze ATRP, whereas other complexes preferred redox-initiated free radical polymerization. Kinetic measurements along with additional mechanistic and computational studies show that a metathesis-inactive ruthenium species, generated in situ from the ruthenium benzylidene complexes, is the active catalyst in ATR reactions. Based on data from (1) H, (13)C, and (31)P NMR spectroscopy and X-ray crystallography, we suspect that this ATRA-active species is a RuxCly(PCy3)z complex.

  1. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice

    International Nuclear Information System (INIS)

    Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise

  2. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice.

    Science.gov (United States)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning; Wang, Miao; Chen, Mu; Hou, Jinsong; Huang, Hongzhang

    2016-08-26

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. PMID:27343556

  3. All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation

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    Birong Zhou

    2012-01-01

    Full Text Available Background. All-trans-retinoic acid (atRA is effective for many proliferative diseases. We investigated the protective effects of atRA against atherosclerosis. Methods. Rabbits were randomly allocated to receive basal diet or an HFD for 4 weeks. HFD group then received rosuvastatin (3 mg/day, atRA (5 mg/kg/day, or the same volume of vehicle, respectively, for next 8 weeks. Results. HFD group showed increases in plasma lipids and aortic plaque formation. P-selectin expression and fibrinogen binding on platelets or deposition on the intima of the aorta also increased significantly as did the levels of TNF-α, IL-6, and fibrinogen in plasma. After 8 weeks of treatment with atRA, there was a significant decrease in plasma lipids and improvement in aortic lesions. AtRA also inhibited the expression of P-selectin and fibrinogen binding on platelets and deposition on the intima of the aorta. Conclusion. AtRA can ameliorate HFD-induced AS in rabbits by inhibiting platelet activation and inflammation.

  4. Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus

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    van Hoek Monique L

    2011-05-01

    Full Text Available Abstract Background Chronic, infected wounds typically contain multiple genera of bacteria, including Staphylococcus aureus, many of which are strong biofilm formers. Bacterial biofilms are thought to be a direct impediment to wound healing. New therapies that focus on a biofilm approach may improve the recovery and healing rate for infected wounds. In this study, cathelicidins and related short, synthetic peptides were tested for their anti-microbial effectiveness as well as their ability to inhibit the ability of S. aureus to form biofilms. Results The helical human cathelicidin LL-37 was tested against S. aureus, and was found to exhibit effective anti-microbial, anti-attachment as well as anti-biofilm activity at concentrations in the low μg/ml range. The effect of peptide chirality and associated protease-resistance was explored through the use of an all-D amino acid peptide, D-LL-37, and in turn compared to scrambled LL-37. Helical cathelicidins have been identified in other animals such as the Chinese cobra, Naja atra (NA-CATH. We previously identified an 11-residue imperfectly repeated pattern (ATRA motif within the sequence of NA-CATH. A series of short peptides (ATRA-1, -2, -1A, as well as a synthetic peptide, NA-CATH:ATRA1-ATRA1, were designed to explore the significance of the conserved residues within the ATRA motif for anti-microbial activity. The CD spectrum of NA-CATH and NA-CATH:ATRA1-ATRA1 revealed the structural properties of these peptides and suggested that helicity may factor into their anti-microbial and anti-biofilm activities. Conclusions The NA-CATH:ATRA1-ATRA1 peptide inhibits the production of biofilm by S. aureus in the presence of salt, exhibiting anti-biofilm activity at lower peptide concentrations than NA-CATH, LL-37 and D-LL-37; and demonstrates low cytoxicity against host cells but does not affect bacterial attachment. The peptides utilized in this anti-biofilm approach may provide templates for a new group of

  5. Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.

    Science.gov (United States)

    March, Thomas H; Cossey, Patricia Y; Esparza, Dolores C; Dix, Kelly J; McDonald, Jacob D; Bowen, Larry E

    2004-01-01

    A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus

  6. Retinoic acid receptor agonists regulate expression of ATP-binding cassette transporter G1 in macrophages.

    Science.gov (United States)

    Ayaori, Makoto; Yakushiji, Emi; Ogura, Masatsune; Nakaya, Kazuhiro; Hisada, Tetsuya; Uto-Kondo, Harumi; Takiguchi, Shunichi; Terao, Yoshio; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Yogo, Makiko; Uehara, Yoshinari; Kagechika, Hiroyuki; Nakanishi, Tsuyoshi; Ikewaki, Katsunori

    2012-04-01

    ABC transporter G1 (ABCG1) plays a pivotal role in HDL-mediated cholesterol efflux and atherogenesis. We investigated whether, and how, retinoic acid receptors (RARs) regulate ABCG1 expression in macrophages. All-trans retinoic acid (ATRA), an RAR ligand, increased ABCG1 protein levels and apoA-I/HDL-mediated cholesterol efflux from the macrophages. Both ATRA and other RAR agonists, TTNPB and Am580, increased major transcripts driven by promoter B upstream of exon 5, though minor transcripts driven by promoter A upstream of exon 1 were only increased by ATRA. The stimulatory effects of ATRA on ABCG1 expression were completely abolished in the presence of RAR/RXR antagonists but were only partially canceled in the presence of an LXR antagonist. Adenovirus with overexpressed oxysterol sulfotransferase abolished the LXR pathway, as previously reported, and ATRA-responsiveness in ABCA1/ABCG1 expressions were respectively attenuated by 38 and 22% compared to the control virus. Promoter assays revealed that ABCG1 levels were regulated more by promoter B than promoter A, and ATRA activated promoter B in a liver X receptor-responsive element (LXRE)-dependent manner. Further, LXRE-B in intron 7, but not LXRE-A in intron 5, enhanced ATRA responsiveness under overexpression of all RAR isoforms-RARα/β/γ. In contrast, the activation of promoter B by TTNPB depended on LXRE-B and RARα, but not on RARβ/γ. Finally, chromatin immunoprecipitation and gel-shift assays revealed a specific and direct repeat 4-dependent binding of RARα to LXRE-B. In conclusion, RAR ligands increase ABCA1/G1 expression and apoA-I/HDL-mediated cholesterol efflux from macrophages, and modulate ABCG1 promoter activity via LXRE-dependent mechanisms.

  7. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    Science.gov (United States)

    Zhang, Ting; Xiong, Hui; Zohra Dahmani, Fatima; Sun, Li; Li, Yuanke; Yao, Li; Zhou, Jianping; Yao, Jing

    2015-04-01

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects.

  8. A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomi Hirako

    Full Text Available We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.

  9. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-07-17

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway.

  10. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

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    Campione E

    2016-04-01

    Full Text Available Elena Campione,1 Roberta Gaziano,2 Daniele Marino,2 Augusto Orlandi3 1Department of Dermatology, 2Department of Microbiology, 3Department of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy Purpose: Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results: We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion: This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. Keywords: all-trans retinoic acid, fungistatic activity, fungal infections

  11. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    International Nuclear Information System (INIS)

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH–ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH–ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH–ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH–ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects. (paper)

  12. Induction of apoptosis and change of bcl—2 expression in macrophage Ana—1 cells by all—trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    YINDELING; XIUHAIREN; 等

    1996-01-01

    Macrophage cells play an important role in the initiation and regulation of the immune response.All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids)affect a large number of biological processes.Recently,retinoids have been shown promise in the therapy and prevention of various cancers.However,many interesting questions related to the activities of retinoids remain to be answered:(I) Molecular mechanisms by which retinoids exert their effects;(Ⅱ)why the clinical uses of retinoids give undesirable side effects of varying severity with a higher frequency of blood system symptoms;(Ⅲ)little is known for its impacts on macrophage cells etc.We set up this experiment,therefore,to examine the apoptosis of ATRA on macrophage Ana-1 cell line.Apoptosis of the cells was quantitated,after staining cells with propidium iodide(PI),by both accounting nuclear condensation and flow cytometry.When the cells were treated with ATRA at or higher than 1μM for more than 24h,significant amount of the apoptotic cells was observed.Induction of apoptosis of Ana-1 cells by ATRA was in time-and dose-dependent manners,exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD).ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2,as detected by Northern blot analysis.The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD.In conclusion,ATRA can induce apoptosis in macrophage cells,which may be helpful in understanding of immunological functions retinoids.

  13. All-TRANS RETINOIC ACID INTERFERES DEVELOPMENT OF PULMONARY HYPERTENSION INDUCED BY MONOCROTALINE IN RATS

    Institute of Scientific and Technical Information of China (English)

    秦玉明; 周爱卿; 贲晓明; 沈捷; 梁瑛; 李奋

    2001-01-01

    Objective To determine whether all-trans retinoic acid (atRA) affects the metabolism of collagen in main pulmonary artery and exerts an inhibitory effect in rats with pulmonary hypertension induced by monocrotaline . Methods All rats (n=72) were divided into 3 groups as control, model, and atRA . In model and atRA groups, rats (n=48) were assigned at random to be given a single subcutaneous injection of monocrotaline (60mgg/kg) and administrated with either atRA (30rng·kg-1·d-1) for atRA group or saline through oral-gastro intubation for model group. In control group, rats (n=24) received a single subcutaneous injection of an equal volume of 0. 9% saline. On day 7, 14,21 and 28 after monocrotaline or saline injection, cardiovascular catheters were inserted into the pulmonary artery of rats in each group to examine their mean pulmonary artery pressure, in addition with their hydroxyproline content determined by chromometry. Results In comparison with the control rats, the mean pulmonary artery pressure of rats in model group increased significantly on day 21 and up to the peak on day 28 (P<0.01), while their hydroxyproline contents decreased significantly on day 14 ( P < 0.05) and increased significantly on day 21 and 28. The atRA group when compared with the model group show reduction in the content of hydroxyproline and the mean pulmonary artery pressure ( P < 0.01 ). Conclusion The atRA inhibits the accumulation of collagen in main pulmonary artery and interferes the development of pulmonary hypertension which might elicit favorable geometric remodeling of rat pulmonary hypertension induced by monocrotaline.

  14. Identification and characterization of an antennae-specific aldehyde oxidase from the navel orangeworm.

    Directory of Open Access Journals (Sweden)

    Young-Moo Choo

    Full Text Available Antennae-specific odorant-degrading enzymes (ODEs are postulated to inactivate odorant molecules after they convey their signal. Different classes of insect ODEs are specific to esters, alcohols, and aldehydes--the major functional groups of female-produced, hydrophobic sex pheromones from moth species. Esterases that rapidly inactive acetate and other esters have been well-studied, but less is known about aldehyde oxidases (AOXs. Here we report cloning of an aldehyde oxidase, AtraAOX2, from the antennae of the navel orangeworm (NOW, Amyelois transitella, and the first activity characterization of a recombinant insect AOX. AtraAOX2 gene spans 3,813 bp and encodes a protein with 1,270 amino acid residues. AtraAOX2 cDNA was expressed in baculovirus-infected insect Sf21 cells as a ≈280 kDa homodimer with 140 kDa subunits. Recombinant AtraAOX2 degraded Z11Z13-16Ald and plant volatile aldehydes as substrates. However, as expected for aldehyde oxidases, recombinant AtraAOX2 did not show specificity for Z11Z13-16Ald, the main constituent of the sex pheromone, but showed high activity for plant volatile aldehydes. Our data suggest AtraAOX2 might be involved in degradation of a diversity of aldehydes including sex pheromones, plant-derived semiochemicals, and chemical cues for oviposition sites. Additionally, AtraAOX2 could protect the insect's olfactory system from xenobiotics, including pesticides that might reach the sensillar lymph surrounding the olfactory receptor neurons.

  15. Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat.

    Directory of Open Access Journals (Sweden)

    Nadja Blagitko-Dorfs

    Full Text Available All-trans retinoic acid (ATRA has only limited single agent activity in AML without the PML-RARα fusion (non-M3 AML. In search of a sensitizing strategy to overcome this relative ATRA resistance, we investigated the potency of the HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60 and primary AML blasts. Entinostat alone induced robust differentiation of both cell lines, which was enhanced by the combination with ATRA. This "priming" effect on ATRA-induced differentiation was at least equivalent to that achieved with the DNA hypomethylating agent decitabine, and could overall be recapitulated in primary AML blasts treated ex vivo. Moreover, entinostat treatment established the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of the RARβ2 gene, an essential mediator of retinoic acid (RA signaling in different solid tumor models. Similarly, RARβ2 promoter hypermethylation (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent could be partially reversed by decitabine in the two cell lines. Re-induction of the epigenetically silenced RARβ2 gene was achieved only when entinostat or decitabine were given prior to ATRA treatment. Thus in this model, reactivation of RARβ2 was not necessarily required for the differentiation effect, and pharmacological RARβ2 promoter demethylation may be a bystander phenomenon rather than an essential prerequisite for the cellular effects of decitabine when combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to the differentiation-inducing effects of ATRA, entinostat is at least as active as decitabine, and both act in part independently from RARβ2. Further investigation of this treatment combination in non-M3 AML patients is therefore warranted, independently of RARβ2 gene silencing by DNA methylation.

  16. Effects of TrkB-BDNF signal pathway on synthesis and secretion of vascular endothelial growth factor in human neuroblastoma cells%TrkB-BDNF信号通路对神经母细胞瘤细胞分泌血管内皮生长因子的影响

    Institute of Scientific and Technical Information of China (English)

    李坤霞; 李爱敏; 张继红

    2011-01-01

    Objective To study the effects of TrkB-BDNF signal pathway on the synthesis and secretion of vascular endothelial growth factor (VEGF) in human neuroblastoma cells (NB). Methods TrkB protein expression in SY5Y cells before and after all-trans-retinoicacid (ATRA) treatment was detected by Western blot. p-TrkB protein expression in SY5Y cells before and after the treatment of ATRA along with BDNF was also detected by Western blot. VEGF concentrations in the SY5Y cell culture supernatants were measured using ELISA after the treatment with ATRA, BDNF, tyrosine kinase inhibitor K252a and PI3k inhibitor LY294002. Results TrkB protein was undetectable in SY5Y cells before ATRA treatment. After the treatment of 1, 10 and 100 nM/L ATRA for five days, TrkB protein was expressed in SY5Y cells and the TrkB protein level increased with the increasing ATRA concentration. p-TrkB protein was not expressed in SY5Y cells treated only with 10 nM/L ATRA, but it was detectable after the treatment of ATRA along with BDNF. VEGF concentrations in the group treated with ATRA + BDNF were significantly higher than those in the untreated control and the ATRA alone treatment groups ( P < 0.01 ). VEGF concentrations in the K252a pretreated ATRA + BDNF group were significantly lower than those in the group treated with ATRA + BDNF ( P < 0.05 ). VEGF concentrations in the LY294002 treatment group (ATRA + LY294002 + BDNF group) were also significantly lower than those in the group treated with ATRA + BDNF ( P < 0. 01 ). Conclusions Activation of TrkB-BDNF signal pathway may increase the synthesis and secretion of VEGF in human NB cells. The synthesis and secretion of VEGF can be inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway PI3K/Akt with LY294002.%目的:探讨TrkB-BDNF信号通路对神经母细胞瘤(NB)细胞SH-SYSY分泌血管内皮生长因子(VEGF)的影响.方法:Western blot方法检测全反式维甲酸(ATRA

  17. Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells.

    Science.gov (United States)

    Falanga, A; Consonni, R; Marchetti, M; Locatelli, G; Garattini, E; Passerini, C G; Gordon, S G; Barbui, T

    1998-07-01

    All-trans-retinoic acid (ATRA) downregulates the expression of two cellular procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human promyelocytic leukemia cells. To evaluate whether or not changes of the procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto-differentiation process, we have characterized the effect of ATRA on the TF and CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4-derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental cells of three synthetic retinoid analogues, ie: AM580 (selective for the retinoic acid receptor [RAR] alpha), capable to induce the granulocytic differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437 (selective for RARgamma), both lacking this capability. Cells were treated with either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on cell differentiation was evaluated by morphologic changes, cell proliferation, nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33 and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient plasmas. Further TF and CP have been characterized and quantified in cell-sample preparations by chromogenic and immunological assays. In the first series of experiments, ATRA downregulates both TF and CP in NB4 parental cells, as expected. However, in the differentiation-resistant cell lines, it induced a significant loss of TF but had little or no effect on CP. In a second series of experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto-differentiating effects and did not affect CP levels. On the other hand, in the same cells the TF expression was reduced by ATRA

  18. Reduction of stimulated sodium iodide symporter expression by estrogen receptor ligands in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Jang, DooRye; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Katzenellenbogen, John A., E-mail: jkatzene@illinois.ed [Department of Chemistry, University of Illinois, Urbana, IL 61801 (United States); Kim, Dong Wook, E-mail: kimdw@chonbuk.ac.k [Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2011-02-15

    Purpose: The sodium iodide symporter (NIS) mediates active iodide uptake in lactating breast tissue, and when its levels are enhanced by all-trans retinoic acid (atRA), NIS has been proposed as a target for the imaging and radiotherapy of breast cancer. Importantly, the estrogen receptor {alpha} (ER{alpha}) is an important regulator of atRA induced NIS gene expression in breast cancer cells. In this study, we investigated the effect of an ER agonist (17{beta}-estradiol, E{sub 2}) or antagonist [trans-hydroxytamoxifen (TOT) or raloxifene (RAL)] treatment on the regulation of NIS gene expression and iodide uptake in an ER{alpha}-positive breast cancer (MCF-7) model. Methods: NIS functional activity was measured in vitro by {sup 125}I uptake assay after incubation with E{sub 2} (from 10{sup -15} to 10{sup -5} M), TOT (from 5x10{sup -8} to 5x10{sup -6} M), or RAL (from 5x10{sup -8} to 5x10{sup -6} M) in the presence or absence of atRA (10{sup -7} M). Under the same conditions, NIS mRNA expression was examined by reverse transcriptase polymerase chain reaction. Athymic mice with MCF-7 xenograft tumors were treated with atRA alone or atRA together with E{sub 2} to evaluate the change of {sup 125}I uptake in tumor tissues in vivo. Results: In the iodide uptake study in cells, E{sub 2}, TOT, or RAL treatment alone did not stimulate {sup 125}I uptake. However, when iodide uptake was stimulated by atRA, cotreatment with E{sub 2}, TOT or RAL decreased {sup 125}I uptake in a concentration-dependent manner. The hormone effects on NIS mRNA expression levels in MCF-7 cells were similar. The results of the in vivo biodistribution study showed that {sup 125}I uptake was reduced 50% in tumor tissues of mice treated with atRA/E{sub 2} as compared to tumors treated only with atRA. Conclusion: Our results suggest that combination treatment of atRA and ER ligands could limit the functional activity of the NIS gene induced by atRA, thereby compromising its use as a target for diagnosis

  19. A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells.

    Science.gov (United States)

    Song, Guanhua; Shi, Lulu; Guo, Yuqi; Yu, Linchang; Wang, Lin; Zhang, Xiaoyu; Li, Lianlian; Han, Yang; Ren, Xia; Guo, Qiang; Bi, Kehong; Jiang, Guosheng

    2016-01-19

    All-trans retinoic acid (ATRA) treatment yields cure rates > 80% through proteasomal degradation of the PML-RARα fusion protein that typically promotes acute promyelocytic leukemia (APL). However, recent evidence indicates that ATRA can also promote differentiation of leukemia cells that are PML-RARα negative, such as HL-60 cells. Here, gene expression profiling of HL-60 cells was used to investigate the alternative mechanism of impaired differentiation in APL. The expression of peptidylarginine deiminase 4 (PADI4), encoding PAD4, a protein that post-translationally converts arginine into citrulline, was restored during ATRA-induced differentiation. We further identified that hypermethylation in the PADI4 promoter was associated with its transcriptional repression in HL-60 and NB4 (PML-RARα positive) cells. Functionally, PAD4 translocated into the nucleus upon ATRA exposure and promoted ATRA-mediated differentiation. Mechanistic studies using RNAi knockdown or electroporation-mediated delivery of PADI4, along with chromatin immunoprecipitation, helped identify PU.1 as an indirect target and SOX4 as a direct target of PAD4 regulation. Indeed, PAD4 regulates SOX4-mediated PU.1 expression, and thereby the differentiation process, in a SOX4-dependent manner. Taken together, our results highlight an association between PAD4 and DNA hypermethylation in APL and demonstrate that targeting PAD4 or regulating its downstream effectors may be a promising strategy to control differentiation in the clinic. PMID:26673819

  20. Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

    Institute of Scientific and Technical Information of China (English)

    Xia LIU; Lei L(U); Bei-bei TAO; Ai-ling ZHOU; Yi-chun ZHU

    2011-01-01

    Aim:To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy.Methods:Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments,kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements.Results:The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, piasmin activity remained unchanged following atRA treatment.Conclusion:Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

  1. All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription-Independent Mechanism

    Science.gov (United States)

    Quintero Barceinas, Reyna Sara; García-Regalado, Alejandro; Aréchaga-Ocampo, Elena; Villegas-Sepúlveda, Nicolás; González-De la Rosa, Claudia Haydée

    2015-01-01

    All-trans retinoic acid (ATRA) has been used as an antineoplastic because of its ability to promote proliferation, inhibition, and differentiation, primarily in leukemia; however, in other types of cancer, such as lung cancer, treatment with ATRA is restricted because not all the patients experience the same results. The ERK signaling pathway is dysregulated in cancer cells, including lung cancer, and this dysregulation promotes proliferation and cell invasion. In this study, we demonstrate that treatment with ATRA can activate the ERK signaling pathway by a transcription-independent mechanism through a signaling cascade that involves RARα and PI3K, promoting growth, survival, and migration in lung cancer cells. Until now, this mechanism was unknown in lung cancer cells. The inhibition of the ERK signaling pathway restores the beneficial effects of ATRA, reduces proliferation, increases apoptosis, and blocks the cell migration process in lung cancer cells. In conclusion, our results suggest that the combination of ATRA with ERK inhibitor in clinical trials for lung cancer is warranted. PMID:26557664

  2. Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing.

    Science.gov (United States)

    Comptour, Aurélie; Rouzaire, Marion; Belville, Corinne; Bonnin, Nicolas; Daniel, Estelle; Chiambaretta, Frédéric; Blanchon, Loïc; Sapin, Vincent

    2016-01-01

    Vitamin A and its active forms (retinoic acids/RAs) are known to have pro-healing properties, but their mechanisms of action are still poorly understood. This work aimed to identify the cellular and molecular processes by which atRA (all-trans RA) improves wound healing, using an in vivo model of mouse corneal alkali burns and an in vitro cellular human corneal epithelial injury model. Regulation by atRA has been studied on most of the cellular events that occur in wound healing. We investigated the direct influence of atRA on a specific target gene known to be involved in the extracellular matrix (ECM) dynamics, one of the pathways contributing to epithelial repair. Our results demonstrate that atRA promotes corneal epithelial wound healing by acting preferentially on migration. The induction of lysyl oxidase-like 4 (LOXL4) expression by atRA in the corneal epithelium environment was established as essential in the mechanism of atRA-dependent wound healing. Our study describes for the first time a direct link between a retinoic-induced gene and protein, LOXL4, and its general clinical pro-healing properties in ECM dynamics. PMID:27597564

  3. Elevated TrkA receptor expression is associated with all-trans retinoic acid-induced neuroblastoma differentiation.

    Science.gov (United States)

    Gao, Q; Chen, C F; Dong, Q; Hou, L; Chen, X; Zhi, Y L; Li, X; Lu, H T; Zhang, H Y

    2015-10-27

    Neuroblastoma is the most common and one of the deadliest among pediatric tumors; however, a subset of infants with neuroblastoma display spontaneous regression. The mechanism of spontaneous regression remains to be elucidated. TrkA plays an essential role in the differentiation and functionality of neurons; abundant TrkA expression is associated with favorable prognosis of neuroblastoma. All-trans retinoic acid (ATRA), a first-line drug for acute promyelocytic leukemia (APL) treatment, has been shown to induce differentiation and inhibit cell growth. Neuroblastoma tissues in our hospital inpatient were collected, primary cell culture was performed, and the cells were separated and purified to be cell line. Trypan blue exclusion was used to count the numbers of cells alive, morphological changes were observed under the phase-contrast microscope. RT-PCR was used to determine the expression level of TrkA. In this study, a human neuroblastoma cell line was successfully established; in addition, we demonstrated that ATRA induces growth arrest and promotes the differentiation of neuroblastoma cells. In addition, ATRA was shown to significantly increase the levels of TrkA mRNA expression. Therefore, we concluded that the elevated expression of the TrkA receptor is associated with ATRA-induced growth arrest and differentiation o neuroblastoma cells. The results of this study provide a theoretical basis for the clinical application of differentiation-inducing ATRA for neuroblastoma therapy.

  4. Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663

    Directory of Open Access Journals (Sweden)

    Zhuan Zhou

    2011-04-01

    Full Text Available Abstract Background Differentiation of the acute myeloid leukemia (AML cell line HL-60 can be induced by all trans-retinoic acid (ATRA; however, the mechanism regulating this process has not been fully characterized. Methods Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation. Results Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV backbone incorporating the spleen focus forming virus (SFFV-F promoter to drive miR-663 expression, as the CMV (Cytomegalovirus promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro. Conclusions Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies

  5. Vav promotes differentiation of human tumoral myeloid precursors

    International Nuclear Information System (INIS)

    Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders

  6. An Improved Method for Directional Differentiation and Efficient Production of Neurons from Embryonic Stem Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yufeng; FANG Feng; DONG Yongsui; LI Ge; ZHEN Hong; YI Wenlong; XIANG Zhidan

    2005-01-01

    To establish a method of directional differentiation and efficient production of neurons from embryonic stem cells (ES cells) in vitro, based on the 4-/4+ protocol described by Bain, a new method was established to induce ES cells differentiating into neurons by means of three-step differentiation using all-trans retinoic acid (ATRA) combined with astrocyte-conditioned medium (ACM) in Vitro. The totipotency of ES cells was identified by observation of cells' morphology and formations of teratoma in immunocompromised mice. The cells' differentiation was evaluated continuously by the detection of the specific cellular markers of neural stem ceils, neurons and astrocytes,including nestin, NSE and GFAP using immunohistochemistry assay. The NSE positive cells' ratio of the differentiated cells was determined by flow cytometry. It was found that the transparent circular clusters surrounding embryoid bodies induced with combining induction protocol formed just after 24 h and gradually enlarged later. This phenomenon could not be observed in EBs induced only by ATRA. The NSE positive cells' ratio irthe cells induced with ATRA and ACM was higher than that of the cells induced by ATRA at different time points of differentiation, and finally reached up to 73.5 % among the total differentiated population. It was concluded that ES cells could be induced into neurons with high purity and yield by means of inducing method combining with ATRA and ACM.

  7. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.

    Science.gov (United States)

    Martelli, Maria Paola; Gionfriddo, Ilaria; Mezzasoma, Federica; Milano, Francesca; Pierangeli, Sara; Mulas, Floriana; Pacini, Roberta; Tabarrini, Alessia; Pettirossi, Valentina; Rossi, Roberta; Vetro, Calogero; Brunetti, Lorenzo; Sportoletti, Paolo; Tiacci, Enrico; Di Raimondo, Francesco; Falini, Brunangelo

    2015-05-28

    Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. PMID:25795919

  8. Effects of All-trans Retinoic Acid on hTERT Gene Expression and Telomerase Activity of HL-60 Cells

    Institute of Scientific and Technical Information of China (English)

    HEDongmei; ZHANGYuan

    2003-01-01

    Objective: To investigate the effects of all-trans retinoic acid (ATRA) on human telomerase reverse transcriptase (hTERT) protein expression and telomerase activity in HL-60 cells. Methods: The expression of hTERT protein was assayed by immunofluorescence using fluoresce isothiocyanate label and telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay with HL-60 cells untreated or treated with ATRA. Cell cycle was analyzed by flow cytometry. Results: After treatment with 1μmol/L ATRA for 24, 48, 72 h, mean fluorescence intensity of hTERT protein in HL-60 cells was 61.87±4.36, 37.47±2.85, 33.45±2.37,respectively. There was a significant decrease in hTERT protein expression compared to the cells untreated, and the effect had statistically significant difference (P<0.05).Telomerase activity was decreased significantly in HL-60 cells treated with 1μmol/L ATRA for 48, 72h as compared to the cells untreated (P<0.05). Conclusion: ATRA could inhibit telomerase activity and hTERT gene expression in HL-60 cells.

  9. Study of Bcl-2 siRNA Enhancement of Sensitivity of HL-60 Cells to All Trans Retinoic Acid

    Institute of Scientific and Technical Information of China (English)

    Haiyan Hu; Yuan Zhang; Dongmei He

    2008-01-01

    OBJECTIVE To study whether siRNA targeting against the Bcl-2gene can enhance sensitivity of HL-60 cells to all trans retinoic acid (ATRA).METHODS siRNA, which is a leading sequence selected by previous experiments, was transferred into HL-60 cells. At 6 h after transfection, the cells were cultured with ATRA. The cell growth of the HL-60 cells was measured by the MTT assay at 24,48, 72 h. The level of the Bcl-2 protein and ROS (reactive oxygen species) as well as membrane potential of the mitochondria were determined by flowcytometry.RESULTS siRNA significantly increased the inhibitory effect of ATRA on growth of the HL-60 cells. The combination of siRNA with ATRA resulted in a decrease in the Bcl-2 protein level and an increase in the ROS level as well as significantly lowering the mitochondrial membrane potential of the HL-60 cells (P < 0.05).CONCLUSION Effective siRNA targeting of Bcl-2 increases the sensitivity of HL-60 leukemic cells to ATRA by inhibiting the expression of the Bcl-2 protein.

  10. Growth Inhibition and Apoptosis Induced by Retinoic Acid Combined with Interferon Alpha-2a on Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    QIANLi-xin; LIUXun-liang; ZHOUJian-wei; MonicaLiebert; ZOUChang-chun; ZOUChang-ping

    2004-01-01

    To identify new favorable agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer and invesligate the effects of combination of relinoids and interferon α-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods: Four bladder cancer cell lines, grade 1 to 3,and two retinoids, all-trans-retinoic acid(ATRA) ,9.cis retinoic acid(9cRA) ,combined with inteferon α-2a(INF),were used in the study.We compared the competence of these agents to inhibit growth, induce apoptosis, affect the exptession of nuclear retinoid receptors, and modulate STAT1 protein. Resu/ts: Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction, even at higher concentration (10-5M).The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INF α-2a.Combination of ATRA and IFNa-2a induced ~ and Slat 1 expression in three bladder cancer cell lines, ~: The results demonstrated that INFw2a synergize with the inhibitory effect of ATRA and 9c RA on the growth intn'bition and apoptosis of bladder cancer cells in vitro, which suggested that it has a potenlJal intexest for the trealment of transitimml cell carcinmna of bladder.

  11. In silico modelling of a cancer stem cell-targeting agent and its effects on tumour control during radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2016-01-01

    Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA’s cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy. PMID:27573059

  12. Apoptotic effect and mechanisms of AHPN on human skin malignant melanoma cell A375

    Institute of Scientific and Technical Information of China (English)

    Min Pan; Zhenhui Peng; Shengxiang Xiao; Jianwen Ren; Yan Liu; Xiaoli Li; Zhengxiao Li

    2008-01-01

    Objective: To study apoptotic effects of synthetic retinoic acid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid(AHPN) on human skin malignant melanoma A375 cells in comparison with the natural iigand all-trans-retinoic acid(ATRA) in vitro and the mechanisms related to the actions of AHPN. Methods:MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results:Firstly, AHPN promoted apoptosis and G1 arrest in A375 cells compared with ATRA. Secondly, the activity of NF-kB in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conelusion:AHPN,in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-kB.

  13. Potential role of nuclear receptor ligand all-trans retinoic acids in the treatment of fungal keratitis

    Institute of Scientific and Technical Information of China (English)

    Hong-Yan; Zhou; Wei; Zhong; Hong; Zhang; Miao-Miao; Bi; Shuang; Wang; Wen-Song; Zhang

    2015-01-01

    ·Fungal keratitis(FK) is a worldwide visual impairment disease. This infectious fungus initiates the primary innate immune response and, later the adaptive immune response. The inflammatory process is related to a variety of immune cells, including macrophages, helper T cells, neutrophils, dendritic cells, and Treg cells, and is associated with proinflammatory, chemotactic and regulatory cytokines. All-trans retinoic acids(ATRA)have diverse immunomodulatory actions in a number of inflammatory and autoimmune conditions. These retinoids regulate the transcriptional levels of target genes through the activation of nuclear receptors.Retinoic acid receptor α(RAR α), retinoic acid receptor γ(RAR γ), and retinoid X receptor α(RXR α) are expressed in the cornea and immune cells. This paper summarizes new findings regarding ATRA in immune and inflammatory diseases and analyzes the perspective application of ATRA in FK.

  14. AcEST: BP921136 [AcEST

    Lifescience Database Archive (English)

    Full Text Available 04|PA2N_NAJAT Phospholipase A2 natratoxin OS=Naja atra Align length 87 Score (bit) 36.2 E-value 0.099 Report...NAJAT Phospholipase A2 natratoxin OS=Naja atra PE... 36 0.099 sp|Q9I900|PA2D_NAJSP Phospholipase A2, acidic ...S=Na... 30 9.2 sp|P17434|NIFB_RHOCA FeMo cofactor biosynthesis protein nifB OS=... 30 9.2 >sp|A4FS04|PA2N_NA...JAT Phospholipase A2 natratoxin OS=Naja atra PE=1 SV=2 Length = 119 Score = 36.2 bits (82), Expect = 0.099 I

  15. In Situ Catalyst Modification in Atom Transfer Radical Reactions with Ruthenium Benzylidene Complexes.

    Science.gov (United States)

    Lee, Juneyoung; Grandner, Jessica M; Engle, Keary M; Houk, K N; Grubbs, Robert H

    2016-06-01

    Ruthenium benzylidene complexes are well-known as olefin metathesis catalysts. Several reports have demonstrated the ability of these catalysts to also facilitate atom transfer radical (ATR) reactions, such as atom transfer radical addition (ATRA) and atom transfer radical polymerization (ATRP). However, while the mechanism of olefin metathesis with ruthenium benzylidenes has been well-studied, the mechanism by which ruthenium benzylidenes promote ATR reactions remains unknown. To probe this question, we have analyzed seven different ruthenium benzylidene complexes for ATR reactivity. Kinetic studies by (1)H NMR revealed that ruthenium benzylidene complexes are rapidly converted into new ATRA-active, metathesis-inactive species under typical ATRA conditions. When ruthenium benzylidene complexes were activated prior to substrate addition, the resulting activated species exhibited enhanced kinetic reactivity in ATRA with no significant difference in overall product yield compared to the original complexes. Even at low temperature, where the original intact complexes did not catalyze the reaction, preactivated catalysts successfully reacted. Only the ruthenium benzylidene complexes that could be rapidly transformed into ATRA-active species could successfully catalyze ATRP, whereas other complexes preferred redox-initiated free radical polymerization. Kinetic measurements along with additional mechanistic and computational studies show that a metathesis-inactive ruthenium species, generated in situ from the ruthenium benzylidene complexes, is the active catalyst in ATR reactions. Based on data from (1) H, (13)C, and (31)P NMR spectroscopy and X-ray crystallography, we suspect that this ATRA-active species is a RuxCly(PCy3)z complex. PMID:27186790

  16. Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid.

    Science.gov (United States)

    Silvis, Anne M; McCormick, Michael L; Spitz, Douglas R; Kiningham, Kinsley K

    2016-04-01

    Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10μM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2(•-) and H2O2, which correlated with increased levels of MnSOD activity and immuno-reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96h indicating that as the cells became more differentiated, steady-state levels of H2O2 increased in the absence of increases in peroxide-scavenging antioxidants (i.e., glutathione, glutathione peroxidase, and catalase). In addition, ATRA-induced stimulation of NF-M at 48 and 72h was enhanced by decreasing SOD activity using siRNA directed at MnSOD. Finally, treatment with ATRA for 96h in the presence of MnSOD siRNA or PEG-catalase inhibited ATRA induced increases in NF-M expression. These results provide strong support for the hypothesis that changes in steady-state levels of O2(•-) and H2O2 significantly contribute to the process of ATRA-induced differentiation in neuroblastoma, and suggest that retinoid therapy for neuroblastoma could potentially be enhanced by redox-based manipulations of superoxide metabolism to improve patient outcome.

  17. All-trans retinoic acid as a single agent induces complete remission in a patient with acute leukemia of M2a subtype

    Institute of Scientific and Technical Information of China (English)

    陈子兴; 王阳; 王玮; 贡静霞; 薛永权

    2002-01-01

    Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.

  18. All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo.

    Science.gov (United States)

    Ma, Hayley S; Greenblatt, Sarah M; Shirley, Courtney M; Duffield, Amy S; Bruner, J Kyle; Li, Li; Nguyen, Bao; Jung, Eric; Aplan, Peter D; Ghiaur, Gabriel; Jones, Richard J; Small, Donald

    2016-06-01

    FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)(+) LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD(+) cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD(+) cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD(+) patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces Bcl6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with FLT3 mutations. PMID:27103744

  19. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.

    Science.gov (United States)

    Wu, Lizhi; Chaudhary, Sandeep C; Atigadda, Venkatram R; Belyaeva, Olga V; Harville, Steven R; Elmets, Craig A; Muccio, Donald D; Athar, Mohammad; Kedishvili, Natalia Y

    2016-01-01

    UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. The results of this study indicate that treatment with UAB30 results in upregulation of genes responsible for the uptake and metabolism of all-trans-retinol to all-trans-retinoic acid (ATRA), the natural agonist of RAR nuclear receptors. Consistent with the increased expression of these genes, the steady-state levels of ATRA are elevated in human skin rafts. In ultraviolet B (UVB) irradiated mouse skin, the expression of ATRA target genes is found to be reduced. A reduced expression of ATRA sensitive genes is also observed in epidermis of mouse models of UVB-induced squamous cell carcinoma and basal cell carcinomas. However, treatment of mouse skin with UAB30 prior to UVB irradiation prevents the UVB-induced decrease in expression of some of the ATRA-responsive genes. Considering its positive effects on ATRA signaling in the epidermis and its low toxicity, UAB30 could be used as a chemoprophylactic agent in the treatment of non-melanoma skin cancer, particularly in organ transplant recipients and other high risk populations. PMID:27078158

  20. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    To compare survival in Acute Promyelocytic Leukemia (APL) patients treated with or without All-Trans Retinoic Acid (ATRA). Longitudinal, comparative study. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or PML/RAR macro re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other retinoids). All patients having history of cardiac failure (LVEF 150 macro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox (Proportional hazard) regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival (OS), Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality. (author)

  1. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.

    Directory of Open Access Journals (Sweden)

    Lizhi Wu

    Full Text Available UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. The results of this study indicate that treatment with UAB30 results in upregulation of genes responsible for the uptake and metabolism of all-trans-retinol to all-trans-retinoic acid (ATRA, the natural agonist of RAR nuclear receptors. Consistent with the increased expression of these genes, the steady-state levels of ATRA are elevated in human skin rafts. In ultraviolet B (UVB irradiated mouse skin, the expression of ATRA target genes is found to be reduced. A reduced expression of ATRA sensitive genes is also observed in epidermis of mouse models of UVB-induced squamous cell carcinoma and basal cell carcinomas. However, treatment of mouse skin with UAB30 prior to UVB irradiation prevents the UVB-induced decrease in expression of some of the ATRA-responsive genes. Considering its positive effects on ATRA signaling in the epidermis and its low toxicity, UAB30 could be used as a chemoprophylactic agent in the treatment of non-melanoma skin cancer, particularly in organ transplant recipients and other high risk populations.

  2. Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet's disease: a study in Algerian patients.

    Science.gov (United States)

    Djeraba, Zineb; Boumedine, Karim; Arroul-Lammali, Amina; Otmani, Fifi; Belguendouz, Houda; Touil-Boukoffa, Chafia

    2014-02-01

    Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD. PMID:24369064

  3. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  4. Protective effect of ginsenoside Rb1 against intestinal ischemia-reperfusion induced acute renal injury in mice.

    Directory of Open Access Journals (Sweden)

    Qian Sun

    Full Text Available Ginsenoside Rb1 (RB1, the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA was used as an inhibitor of NF-E2-related factor-2 (Nrf2 signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1 sham group, (2 IIR group, (3 RB1 group, (4 sham + ATRA group, (5 IIR + ATRA group, and (6 RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO. Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN, serum creatinine (Scr and neutrophil gelatinase-associated lipocalin (NGAL, which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1 and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE pathway.

  5. Study of irradiation creep of vanadium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Smith, D.L. [Argonne National Lab., IL (United States)] [and others

    1997-08-01

    Thin-wall tubing was produced from the 832665 (500 kg) heat of V-4 wt.% Cr-4 wt.% Ti to study its irradiation creep behavior. The specimens, in the form of pressurized capsules, were irradiated in Advanced Test Reactor and High Flux Isotope Reactor experiments (ATR-A1 and HFIR RB-12J, respectively). The ATR-A1 irradiation has been completed and specimens from it will soon be available for postirradiation examination. The RB-12J irradiation is not yet complete.

  6. Leukocyte and leukocyte function

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950368 A study on the relationship hetween morphol-ogy and gene hepterogeneity in acute promyelocyticleukemia.XIONG Shumin(熊树民),et al.shanghaiHematol Instit & Ruijin Hosp,Shanghai,200025.ChinJ Intern Med 1995;34(3):165-168.Aucte promyelocytic leukemia (APL) can be treatedby all-trans retinoic acid (ATRA) with high completeremission rate.50 cases of APL diagnosed morphologi-cally were studied on their cytogenetics,molecular bi-ology and response to treatment with ATRA.Fortyfive cases showed chromosomal translocation t(5;17)and PML/RAR α fusion gene (PML+RARα+APL)

  7. Long-distance retinoid signaling in the zebra finch brain.

    Directory of Open Access Journals (Sweden)

    Tina C Roeske

    Full Text Available All-trans retinoic acid (ATRA, the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1 ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2 Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN, receptor expression is dynamically regulated in a circadian and age-dependent manner. (3 High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the

  8. Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated Hepatic and Pulmonary Immune Responses in Ascaris suum-Infected Swine Are Increased by Retinoic Acid▿ †

    OpenAIRE

    Dawson, Harry; Solano-Aguilar, Gloria; Beal, Madeline; Beshah, Ethiopia; Vangimalla, Vandana; Jones, Eudora; Botero, Sebastian; Joseph F. Urban

    2009-01-01

    Pigs infected with Ascaris suum or controls were given 100 μg (low-dose) or 1,000 μg (high-dose) all-trans retinoic acid (ATRA)/kg body weight in corn oil or corn oil alone per os on days after inoculation (DAI) −1, +1, and +3 with infective eggs. Treatment with ATRA increased interleukin 4 (IL4) and IL12p70 in plasma of infected pigs at 7 DAI and augmented bronchoalveolar lavage (BAL) eosinophilia observed at 7 and 14 DAI. To explore potential molecular mechanisms underlying these observatio...

  9. Effect of All-trans Retinoic Acid on Liver Fibrosis Induced by Common Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hui WANG; Zili DAN; Haiyan JIANG

    2008-01-01

    Summary: The aim of this study was to investigate the effect and possible mechanism of all-trans retinoic acid (ATRA) on liver fibrosis induced by common bile duct ligation (CBDL) in rats. Fifty-three female Wistar rats were randomly divided into 5 groups: sham operation group (group J, 5 animals) and groups A, B, C and D (12 animals in each group). The rats in groups A, B, C and D were subjected to CBDL to induce liver fibrosis, while those in group J to sham operation. From the 3rd week the rats in groups B, C and D respectively received daily administration of ATRA via gastric tube at three different doses [0.1, 1.5 and 7.5 mg/kg body weight (BW)]. Animals were sacrificed at 6th week. Rats' liver tissues were observed for pathologic changes under a light microscope. The protein levels of type Ⅰ collagen (COL Ⅰ), matrix metalloproteinase-2 (MMP2), MMP13 and tissue inhibitors of metalloproteinase-1 (TIMP-1) in liver tissues were determined by immunohistochemical techniques. The expression levels of TGF-β1 and CTGF mRNA in liver tissues were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that loss of normal hepatic architecture and formation of obvious fibrosis were observed in group A, while ATRA treatment for 4 weeks notably alleviated the pathological changes of hepatocytes. The expression of COL Ⅰ and TIMP-1 proteins in group A was increased, while decreased in ATRA-treated CBDL groups (P<0.05). ATRA (1.5 and 7.5 mg/kg BW) reduced the expression levels of COL Ⅰprotein more greatly than that of 0.1 mg/kg BW (P<0.05). ATRA treatment increased the protein levels of MMP2 and MMP13. The expression levels of TGF-β1 and CTGF mRNA in group A were increased. In comparison with group A, the mRNA levels of TGF-β1 and CTGF in ATRA-treated CBDL groups were significantly decreased (P<0.05). It was concluded that ATRA could inhibit CBDL-induced liver fibrosis in rats by suppressing the expression of TGF

  10. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells.

    Directory of Open Access Journals (Sweden)

    Zhenya Gao

    Full Text Available All-trans retinoic acid (ATRA plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2 and matrix metalloproteinase 2 (MMP-2 and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19 cells.The effects of ATRA (concentrations from 10-9 to 10-5 mol/l on the expression of retinoic acid receptors (RARs in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10-9 to 10-5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR and enzyme-linked immunosorbent assay (ELISA. The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ.RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10-9 to 10-5 mol/l with a maximum effect observed at 10-6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10-6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135.ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated these cells to secrete BMP-2 and MMP-2.

  11. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    OpenAIRE

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 C...

  12. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    Science.gov (United States)

    Gao, Zhenya; Huo, Lijun; Cui, Dongmei; Yang, Xiao; Zeng, Junwen

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19) cells. Methods The effects of ATRA (concentrations from 10−9 to 10−5 mol/l) on the expression of retinoic acid receptors (RARs) in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10−9 to 10−5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ. Results RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10−9 to 10−5 mol/l) with a maximum effect observed at 10−6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10−6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135. Conclusion ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated

  13. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs. METHODOLOGY/PRINCIPAL FINDINGS: Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered. CONCLUSIONS/SIGNIFICANCE: We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  14. 酪氨酸激酶受体B-脑源性神经营养因子信号传导通路对神经母细胞瘤细胞分泌血管内皮生长因子及基质金属蛋白酶-9的影响%Effects of tyrosine kinase receptor B-brain-derived neurotrophic factor signal pathway on the secretion of vascular endothelial growth factor and matrix metalloproteinase-9 of neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    刘建英; 高惠敏; 李爱敏; 蔡维艳; 初清

    2013-01-01

    目的 探讨酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)-脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)信号传导通路对神经母细胞瘤(neuroblastoma,NB)细胞SH-SY5Y分泌血管内皮生长因子(vascular endothelial growth factor,VEGF)及基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的影响.方法 用全反式维甲酸(all-trans retinoic acid,ATRA)诱导SH-SY5Y细胞表达TrkB,加入外源性BDNF,从而激活TrkB-BDNF信号传导通路及其3条下游信号通路.再用特异性酪氨酸激酶抑制剂K252a阻断TrkB-BDNF信号传导通路;用磷脂酰肌醇-3激酶(phosphatidylinositol 3-hydrox y kinase,PBK)抑制剂LY294002、磷脂酶C抑制剂U73122、丝裂原活化蛋白激酶抑制剂U0126分别阻断TrkB-BDNF的3条相应下游信号传导通路.采用酶联免疫吸附法检测细胞培养上清液中VEGF及MMP-9含量.结果 ATRA+ BDNF组VEGF[(485.89±109.99) pg/ml]及MMP-9[(15.73±1.72) pg/ml]含量明显高于对照组及ATRA组(P <0.05);ATRA+ BDNF+ K252a组VEGF[(272.42±86.33) pg/ml]及MMP-9[(5.25±1.44) pg/ml]含量明显低于ATRA+ BDNF组(P<0.05),与对照组及ATRA组比较差异无统计学意义(P>0.05);ATRA+ BDNF+ LY294002组VEGF[(314.12±24.68) pg/ml]及MMP-9[(4.91±1.08) pg/ml]含量明显低于ATRA+ BDNF组(P<0.05),与对照组及ATRA组比较差异无统计学意义(P >0.05);ATRA+ BDNF+ U73122组VEGF[(444.08±64.49) pg/ml]及MMP-9[(13.28±3.38) pg/ml]含量与ATRA+ BDNF组比较差异无统计学意义(P>0.05).ATRA+ BDNF+ U0126组VEGF[(429.97±19.95) pg/ml]及MMP-9[(13.96±4.45) pg/ml]含量与ATRA+ BDNF组比较差异无统计学意义(P>0.05).结论 激活TrkB-BDNF信号传导通路可促进NB细胞合成、分泌VEGF及MMP-9.TrkB-BDNF信号传导通路可能通过进一步激活其下游PI3 K/Akt通路来促进VEGF及MMP-9的合成及分泌,用K252a阻断TrkB-BDNF信号通路、LY294002阻断其下游PI3K通路均可有效抑制NB细胞合成及分泌VEGF及MMP-9

  15. Acute and chronic exposure in mussel (aulacomya ater) and clam (semelle solida) with Cs137

    International Nuclear Information System (INIS)

    Two of the most common Peruvian benthonic molluscs, have been shown to be effective concentrators of Cesium-137 and have also proven useful as indicators of that radionuclide in their natural environment, according with results in this paper. However the clam is a better indicator, when determining environmental acute release of Cesium-137 due to reactor accidents, nuclear tests, accidents in nuclear ships, submarines and radioactive material transport, and the mussel for a continuous monitoring of environmental radio contaminant levels. (author). 11 refs

  16. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  17. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  18. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Science.gov (United States)

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Li, Zhengzhe; Chen, Yibang; Evans, Todd; Chuang, Peter; Das, Bhaskar; He, John Cijiang

    2011-01-01

    Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  19. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy : long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

    NARCIS (Netherlands)

    Sanz, Miguel A.; Montesinos, Pau; Vellenga, Edo; Rayon, Consuelo; de la Serna, Javier; Parody, Ricardo; Bergua, Juan M.; Leon, Angel; Negri, Silvia; Gonzalez, Marcos; Rivas, Concha; Esteve, Jordi; Milone, Gustavo; Gonzalez, Jose D.; Amutio, Elena; Brunet, Salut; Garcia-Larana, J.; Colomer, Dolors; Calasanz, Maria J.; Chillon, Carmen; Barragan, Eva; Bolufer, Pascual; Lowenberg, Bob

    2008-01-01

    A previous report of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia result

  20. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy : characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    Montesinos, Pau; Bergua, Juan M.; Vellenga, Edo; Rayon, Chelo; Parody, Ricardo; de la Serna, Javier; Leon, Angel; Esteve, Jordi; Milone, Gustavo; Deben, Guillermo; Rivas, Concha; Gonzalez, Marcos; Tormo, Mar; Diaz-Mediavilla, Joaquin; Gonzalez, Jose D.; Negri, Silvia; Amutio, Elena; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2009-01-01

    Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid ( ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prog

  1. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- a

  2. First report of (homo)anatoxin-a and dog neurotoxicosis after ingestion of benthic cyanobacteria in The Netherland

    NARCIS (Netherlands)

    Faassen, E.J.; Harkema, L.; Begeman, L.; Lürling, M.

    2012-01-01

    In April and May 2011, three dogs died and one dog became ill after swimming in Lake IJmeer (The Netherlands). At the time, the lake was infested with the benthic cyanobacterial species Phormidium. A Eurasian Coot (Fulica atra) and a Black-headed Gull (Chroicocephalus ridibundus) also died near Lake

  3. First report of (homo)anatoxin-a and dog neurotoxicosis after ingestion of benthic cyanobacteria in The Netherlands

    NARCIS (Netherlands)

    Faassen, E.J.; Harkema, H.; Begemann, L.L.J.; Lürling, M.F.L.L.W.

    2012-01-01

    In April and May 2011, three dogs died and one dog became ill after swimming in Lake IJmeer (The Netherlands). At the time, the lake was infested with the benthic cyanobacterial species Phormidium. A Eurasian Coot (Fulica atra) and a Black-headed Gull (Chroicocephalus ridibundus) also died near Lake

  4. 78 FR 7387 - Continuation of Farm Service Agency 2008 Farm Bill Programs

    Science.gov (United States)

    2013-02-01

    ... Income Loss Contract Program (MILC), Dairy Product Price Support Program (DPPSP), Dairy Indemnity Payment... eligible producers in October 2013. As the 2008 Farm Bill did not authorize advance direct payments for the... ATRA through September 30, 2013, with minor modifications. MILC compensates enrolled dairy...

  5. AcEST: DK958578 [AcEST

    Lifescience Database Archive (English)

    Full Text Available A0S7R2_ONCHC Class III peroxidase OS=Oncidium Gower Ra... 228 4e-58 tr|A5AGY5|A5A...>tr|A0S7R2|A0S7R2_ONCHC Class III peroxidase OS=Oncidium Gower Ramsey PE=2 SV=1 Length = 332 Score = 228 bit

  6. Experiment list: SRX014758 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SRX014758 hg19 Histone H3K27me3 Blood NB-4 Primary Tissue=Blood|Site of Extraction=Bone Marrow|Tissue Diagno...sis=Leukemia 15859913,93.5,4.4,416 GSM468188: H3K27me3 ChIP-seq NB4 24hoursATRA, JM

  7. Ultrastructural examination of the pycnidia and conidia of the genus Opegrapha (Arthoniales, Ascomycota

    Directory of Open Access Journals (Sweden)

    Anetta Wieczorek

    2013-12-01

    Full Text Available The paper presents a summary of examinations on the variation of pycnidia and conidia of the following Opegrapha species occurring in Poland: O. atra, O. calcarea, O. dolomitica, O. gyrocarpa, O. niveoatra, O. rupestris, O. varia, O. vermicellifera, O. viridis and O. vulgata.

  8. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujiki, Atsushi [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sugita, Kanji [Department of Pediatrics, University of Yamanashi, Yamanashi (Japan); Hosoi, Hajime [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  9. Current management of newly diagnosed acute promyelocytic leukemia.

    Science.gov (United States)

    Cicconi, L; Lo-Coco, F

    2016-08-01

    The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease. PMID:27084953

  10. Management of acute promyelocytic leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet

    NARCIS (Netherlands)

    M.A. Sanz (Miguel Angel); D. Grimwade (David); M.S. Tallman (Martin); B. Löwenberg (Bob); P. Fenaux (Pierre); E.H. Estey (Elihu); T. Naoe (Tomoki); E. Lengfelder (Eva); T. Büchner (Thomas); H. Döhner (Hartmut); A.K. Burnett (Alan); F. Lo-Coco (Francesco)

    2009-01-01

    textabstractThe introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with

  11. Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; van Crevel, Reinout;

    2015-01-01

    inhibited cytokine responses upon restimulation of monocytes, and this effect was exerted through increased expression of SUV39H2, a histone methyltransferase that induces the inhibitory mark H3K9me3. H3K9me3 at promoter sites of several cytokines was up-regulated by ATRA, and inhibition of SUV39H2 restored...

  12. Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

    Science.gov (United States)

    Perrotta, Ida; Perri, Mariarita; Santoro, Marta; Panza, Salvatore; Caroleo, Maria C; Guido, Carmela; Mete, Annamaria; Cione, Erika; Aquila, Saveria

    2015-01-01

    Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

  13. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    Science.gov (United States)

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  14. The Retinoic Acid Receptor-a Mediates Human T-Cell Activation and Th2 Cytokine Production

    Science.gov (United States)

    We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-g and TNF-a expression by activated human T cells and reducing the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated ...

  15. Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Juan Shen; Jing Bo Shi; Fei Hu Chen; Yuan Wang; Jing Jing Ruan; Yua Huang

    2009-01-01

    A series of retinoate and retinamide derivatives were designed, synthesized, and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays (FCM). All compounds showed cytotoxicity, especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-traus retinoic acid (ATRA). Furthermore, compound ld could induce NB4 cell lines differentiation efficiently.

  16. Inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Piao; Yang Shi; Pu-Jun Gao

    2003-01-01

    AIM: To study the inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell line SMMC-7721and to explore the mechanism of its effect.METHODS: SMMC-7721 cells were divided into two groups, one treated with all-trans retinoic acid (ATRA) for 5 days and the other as a control group. Light microscope and electron microscope were used to observe the morphological changes. Telomerase activity was analyzed with silver-stained telomere repeated assay protocal (TRAP). Expression of Caspase-3 was demonstrated with western blot.RESULTS: ATRA-treated cells showed differentiation features including small and pyknotic nuclei, densely stained chromatin and fewer microvilli. Besides, ATRA could inhibit the activity of telomerase, promote the expression of Caspase-3 and its activation.CONCLUSION: Telomerase activity and Caspase-3expression are changed in human hepatocellular carcinoma cell line SMMC-7721 treated with all-trans retinioc acid.The inhibition of telomerase activity and the activation of Caspase-3 may be the key steps through which ATRA inhibits the proliferation of SMMC-7721 cell line.

  17. Experimental study of the enhancement effect of aminopeptidase N inhibitor ubenimex on the differentiation induction activity of all-trans-retinoic acid in acute promyeiocytic leukemia cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    钱习军

    2006-01-01

    Objective To investigate the effect of aminopeptidase N inhibitor ubenimex on differentiation induction of alltrans -retinoic acid (ATRA) in acute promyelocytic leukemia (APL) cells and its mechanism. Methods The expression of CD11b was analyzed by flow cytometry and nitroblue-tetrazolium (NBT) reduction assay was per-

  18. Studies of antifungal activity of forsskalea tenacissima

    International Nuclear Information System (INIS)

    Antifungal activity of different extracts from Forsskalea tenacissima prepared by solvent-solvent extraction and vacuum liquid chromatography (VLC) was determined. Extracts were found to be active against Candida albicans, Trichophyton mentagrophyte, Allescheria boydii, Microsporum canis, Aspergillus niger, Drechslera rostrata, Nigrospora oryzae, Stachybotrys atra, Curvularia lunata, Trichophyton semii and Trichophyton schoenleinii. (author)

  19. Contrasting Roles For All-Trans Retinoic Acid in TGF-ß-mediated Induction of Foxp3 and Il10 Genes in Developing Regulatory T Cells

    Science.gov (United States)

    Extrathymic induction of regulatory T cells (Treg) is essential to the regulation of effector T cell responses in the periphery. TGF-ß has been shown to induce Foxp3-expressing Tregs both in vitro and in vivo. More recently, the vitamin A metabolite, all-trans retinoic acid (at-RA), has been found t...

  20. 甲基转移酶在恶性骨肉瘤体外诱导分化过程中的作用%Role of Methyltransferase in Differentiation Induction in vitro of Malignant Osteosarcoma Cells

    Institute of Scientific and Technical Information of China (English)

    张岩; 夏仁云; 陈安民; 冯尔宥; 俞孟

    2006-01-01

    Objective: To observe the change of DNA methyltransferase (Dnmt) in osteosarcoma cell linesdifferentiation induction in vitro, so as to explore the function and relativity of Dnmt in malignant os teosarcoma cell during differentiation induction in vitro. Methods: After in vitro differentiation induction by all trans-retinoic acid (ATRA), morphological and functional changes of the cells were observed. The expression levels of Dnmt and PCNA mRNA were detected by semi-quantitative RT-PCR. Changes of cell cycle were determined by flow cytometry (FCM). Results: After treatment with ATRA, the growth of MG-63 cell was inhibited. The cells underwent morphological and functional differentiation. Alkaline phosphatase activity of the cells was increased. The relative expression levels of Dnmt and PCNA mRNA were decreased remarkably in osteosarcoma cells with the time delayed. Osteosarcoma cells were arrested in G1 phase. Conclusion: ATRA could inhibit cell growth and induce differentiation of MG-63 cells in morphologic and function. The Dnmt regulation directly links to cell cycle and PCNA mRNA levels. Inhibition of the Dnmt mRNA expression in MG-63 cells may be one of the important mechanisms of ATRA inducing differentiation of osteosarcoma cells.

  1. Non-coding RNAs change their expression profile after Retinoid induced differentiation of the promyelocytic cell line NB4

    Directory of Open Access Journals (Sweden)

    Caporaso Maria G

    2010-01-01

    Full Text Available Abstract Background The importance of non-coding RNAs (ncRNAs as fine regulators of eukaryotic gene expression has emerged by several studies focusing on microRNAs (miRNAs. miRNAs represent a newly discovered family of non coding-RNAs. They are thought to be crucial players of human hematopoiesis and related tumorigenesis and to represent a potential tool to detect the early stages of cancer. More recently, the expression regulation of numerous long ncRNAs has been linked to cell growth, differentiation and cancer although the molecular mechanism of their function is still unknown. NB4 cells are promyelocytic cells that can be induced to differentiation upon retinoic acid (ATRA treatment and represent a feasible model to study changes of non coding RNAs expression between cancer cells and their terminally differentiated counterpart. Findings we screened, by microarray analysis, the expression of 243 miRNAs and 492 human genes transcribing for putative long ncRNAs different from miRNAs in NB4 cells before and after ATRA induced differentiation. Our data show that 8 miRNAs, and 58 long ncRNAs were deregulated by ATRA induced NB4 differentiation. Conclusion our data suggest that ATRA-induced differentiation lead to deregulation of a large number of the ncRNAs that can play regulatory roles in both tumorigenesis and differentiation.

  2. Field evidence for the potential of waterbirds as dispensers of aquatic organisms

    NARCIS (Netherlands)

    Charalambidou, I.; Santamaria, L.

    2005-01-01

    Field collections during November of green-winged teal (Anas crecca), mallard (Anas platyrhynchos), and coot (Fulica atra) feces in Denmark, England, and France were used to examine the potential of waterbirds to disperse aquatic plant, algae, and invertebrate species across Europe. A total of 216 f

  3. Retinoic acid exerts dual regulatory actions on the expression and nuclear localization of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2006-05-01

    Interferon regulatory factor-1 (IRF-1), a transcription factor and tumor suppressor involved in cell growth regulation and immune responses, has been shown to be induced by all-trans retinoic acid (ATRA). However, the factors controlling the cellular location and activity of IRF-1 are not well understood. In this study, we examined the expression of IRF-1 and its nuclear localization, DNA-binding activity, and target gene expression in human mammary epithelial MCF10A cells, a model of breast epithelial cell differentiation and carcinogenesis. Following initial treatment with ATRA, IRF-1 mRNA and protein were induced within 2 hrs, reached a peak (>30-fold induction) at 8 hrs, and declined afterwards. IRF-1 protein was predominantly cytoplasmic during this treatment. Although a second dose of ATRA or Am580 (a related retinoid selective for retinoic acid receptor-alpha [RARalpha]), given 16 hrs after the first dose, restimulated IRF-1 mRNA and protein levels to a similar level to that obtained by the first dose, IRF-1 was predominantly concentrated in the nucleus after restimulation. ATRA and Am580 also increased nuclear RARalpha, whereas retinoid X receptor-alpha (RXRalpha)--a dimerization partner for RARalpha, was localized to the nucleus upon second exposure to ATRA. However, ATRA and Am580 did not regulate the expression or activation of signal transducer and activator of transcription-1 (STAT-1), a transcription factor capable of inducing the expression of IRF-1, indicating an STAT-1-independent mechanism of regulation by ATRA and Am580. The increase in nuclear IRF-1 after retinoid restimulation was accompanied by enhanced binding to an IRF-E DNA response element, and elevated expression of an IRF-1 target gene, 2',5'-oligoadenylate synthetase-2. The dual effect of retinoids in increasing IRF-1 mRNA and protein and in augmenting the nuclear localization of IRF-1 protein may be essential for maximizing the tumor suppressor activity and the immunosurveillance

  4. Effects of all-trans-retinoic acid and resveratrol on the gene expression of lysine-specific histone demethylase 1 in human melanoma cells A375%白藜芦醇和全反式维A酸对人黑素瘤细胞株A375 LSD-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐观辉; 李建军; 张建青; 彭友华; 郑锦芬

    2011-01-01

    Objective: To investigate the effects of all-trans- retinoic acid (ATRA) and resveratrol (Res) on the expression of lysine- specific histone demethylase 1 (LSD- 1 ) in human melanoma cells A375. Methods: The inhibitive effects of ATRA and RES on human melanoma cells A375 were measured using MTT colorimetric assay. The morphology of A375 cells was observed by inverted microscope. The expression of LSD- 1 mRNA was detected by RT - PCR. Results: Both ATRA and Res inhibited proliferation of A375 cells. The mRNA of LSD - 1 was significantly decreased in A375 cells treated with 100 μmol/L Res and 25.0 μmol/L ATRA when compared to the control cells (P<0.05). However, there was no significant difference in down-regulation of LSD- 1 between 100 μmol/L Res and 25.0μmol/L ATRA ( P > 0.05). Conclusion: ATRA and Res can inhibit the expression of LSD1, which may play a role against tumors.%目的: 确定白藜芦醇(resveratrol,Res)和全反式维A酸(all-trans-retinoic acid,ATRA)对人黑素瘤细胞株A375赖氨酸特异性组蛋白去甲基化酶 1(LSD-1)基因表达的影响.方法: MTT比色法检测Res和ATRA对A375细胞增殖的抑制;倒置显微镜观察A375细胞形态的变化;RT-PCR方法检测LSD-1的mRNA的表达.结果: Res和ATRA均能抑制A375细胞的增殖.100 μmol/L Res及25.0 μmol/L ATRA均能显著减少人恶性黑素瘤细胞株A375中LSD-1的mRNA的表达, 与对照组比较差异均有统计学意义(P<0.05),但对LSD-1的下调作用无显著差异(P>0.05).结论: 抑制黑色素瘤细胞LSD-1的表达,可能是Res和ATRA抗肿瘤的途径之一.

  5. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  6. Effects of all-trans retinoic acid on airway responsiveness and airway remodeling in rats with asthma%全反视黄酸对哮喘大鼠气道反应性和气道重塑的影响

    Institute of Scientific and Technical Information of China (English)

    李文开; 李云; 钟礼立

    2011-01-01

    目的 观察全反视黄酸(ATRA)对哮喘大鼠气道反应性、气道重塑和肺组织基质金属蛋白酶-9(MMP-9)表达的影响,方法:40只大鼠随机分为5组,每组8只:盐水组、模型组、ATRA组、棉籽油组和布地奈德(BUD)组.后4组经卵清蛋白(OVA)致敏14 d后激发6周,构建大鼠慢性哮喘模型.ATRA组、棉籽油组和BUD组每次激发前分别给予ATRA 50 μg/kg,棉籽油1 mL和BUD 0.32 mg/kg,5组大鼠行气道反应性检测,并测定肺组织MMP-9表达和气道重塑情况.结果 ATRA干预组的气道反应性与盐水组比较差异无统计学意义(P>0.05),MMP-9表达高于盐水组,差异具有统计学意义(P<0.05).ATRA干预组的气道反应性和MMP-9表达均明显低于模型组,气道重塑改变减轻,差异具有统计学意义(P<0.05).结论 早期预防性ATRA于预通过减少肺组织MMP-9表达,可在一定程度上减轻哮喘大鼠的气道重塑和气道高反应性.%Objective To study the effects of all-trans retinoic acid ( ATRA) on airway responsiveness, airway remodeling and expression of matrix metalloproteinas-9 ( MMP-9 ) protein in rats with asthma. Methods Forty rats were randomly divided into five groups; asthma model, normal saline (control), ATKA treatment, cotton oil treatment and budesonide treatment (n =8 each). Asthma was induced by ovalbumin sensitization and challenge in the asthma model, and the ATRA, cotton oil or budesonide treatment groups. ATRA (50 fig/kg) , cotton oil (1 mL) or budesonide (0.32 mg/kg) was administered before ovalbumin challenge in the three treatment groups. Airway responsiveness was assessed. The lung tissues were sampled to detect airway remodeling and the expression of MMP-9 protein by immunohistochemistry. Results The expression of MMP-9 in lung tissues in the ATRA treatment group was significantly higher than that in the control group, but the airway responsiveness in the ATRA treatment group was not significantly different from that in the control

  7. Interference of PAHs and their N-heterocyclic analogs with signaling of retinoids in vitro.

    Science.gov (United States)

    Benísek, Martin; Bláha, Ludek; Hilscherová, Klára

    2008-12-01

    Retinoids are dietary hormones acting through nuclear receptors for retinoic acid, important especially during embryonic development. This study focuses on the disruption of signaling pathways of retinoids by polycyclic aromatic hydrocarbons (PAHs) and their N-heterocyclic analogs (N-PAHs), important environmental contaminants with numerous biological effects. In vitro test with P19/A15 cell line stably transfected with luciferase reporter gene under control of retinoic acid-responsive elements was used to investigate both direct activation of retinoic acid receptors and modulation of response induced by natural ligand all-trans retinoic acid (ATRA) by 26 PAHs and N-PAHs. While none of individual compounds alone activated retinoic acid receptors, many of them modulated ATRA-mediated activity both after 6 h and 24 h exposure. Majority of compounds active after 6h downregulated ATRA-mediated activity (most effective were two analogs of dibenz[a,h]anthracene with LOECs about 185 nM), while most compounds active after 24h upregulated the effects of ATRA (most effective benz[a]acridine and dibenz[a,i]acridine caused 400% induction of ATRA response). Quantitative structure-activity relationship analysis identified molecular volume and dipole moment as the most important descriptors of inhibitory effects after 6h, while length, total molecular energy, gap-HOMO/LUMO and Van der Waals energy are important descriptors for stimulatory effects of PAHs and N-PAHs. This study demonstrates those abundant pollutants such as PAHs and their analogs interfere in vitro with retinoid signaling, which could play role in some in vivo effects of these organic contaminants such as teratogenicity. PMID:18835432

  8. All-trans retinoic acid inhibited angiotensin Ⅱ-induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Yan HE; Ying HUANG; Li ZHOU; Li-min LU; Yi-chun ZHU; Tai YAO

    2006-01-01

    Aim:To determine whether all-trans retinoic acid (atRA) acts to modulate angiotensin Ⅱ (Ang Ⅱ) -induced cardiac fibroblast cell growth and collagen secretion.Methods:Cultured neonatal rat cardiac fibroblasts (CF) were used in the experiment.A 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell growth of the CF;and immunocytochemistry and Western blotting were used to measure the production and secretion of collagen and the expression of transforming growth factor-β1 (TGF-β1) by the CF.Results:atRA (1×10-7 to 1×10-5mol/L) inhibitedtheAngⅡ-induced increase in cell growth of CF (P<0.05).Ang Ⅱ stimulated the secretion of collagen types Ⅰ and Ⅲ by the CF. This eflfect was blocked by AT1 receptor antagonist losartan (1×10-6 mol/L) ,but notbyAT2 receptorantagonistPDl23319 (upto 1×10-6mol/L).Exposure of CF to atRA (1×10-5mol/L) attenuated the Ang Ⅱ-induced increase in the secretion of collagen types I and Ⅲ (P<0.05).atRA (1×10-5mol/L) also blocked the Ang Ⅱ-induced increase in the expression of TGF-β1.Conclusion:atRA inhibits the Ang Ⅱ-induced increase in cell growth and collagen secretion of neonatal rat CF.The effect of atRA is possibly mediated by lowering the TGF-β1 level.These observations support the notion that atRA is a potential candidate for the prevention and therapy of cardiac remodeling.

  9. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  10. All Trans-Retinoic Acid Mediates MED28/HMG Box-Containing Protein 1 (HBP1)/β-Catenin Signaling in Human Colorectal Cancer Cells.

    Science.gov (United States)

    Lee, Ming-Fen; Hsieh, Nien-Tsu; Huang, Chun-Yin; Li, Chun-I

    2016-08-01

    Vitamin A is required for normal body function, including vision, epithelial integrity, growth, and differentiation. All trans-retinoic acid (ATRA), a family member of vitamin A, has been explored in treating acute promyelocytic leukemia and other types of cancer. Dysregulated Wnt/β-catenin signaling and disrupted cadherin-catenin complex often contribute to colorectal malignancy. MED28, a mammalian Mediator subunit, is found highly expressed in breast and colorectal cancers. Our laboratory has also reported that MED28 regulates cell growth, migration, and invasion in human breast cancer cells. In the current study we investigated the effect of ATRA on MED28 and Wnt/β-catenin signaling in colorectal cancer. HCT116, HT29, SW480, and SW620, four human colorectal cancer cell lines representing different stages of carcinogenesis and harboring critical genetic changes, were employed. Our data indicated that regardless of genetic variations among these cells, suppression of MED28 reduced the expression of cyclin D1, c-Myc, and nuclear β-catenin, but increased the expression of E-cadherin and HMG box-containing protein 1 (HBP1) where HBP1 has been described as a negative regulator of the Wnt/β-catenin signaling. The reporter activity of an HBP1 promoter increased upon MED28 knockdown, but decreased upon MED28 overexpression. ATRA reduced the expression of MED28 and mimicked the effect of MED28 suppression in down-regulating Wnt/β-catenin signaling. Taken together, ATRA can reverse the suppressive effect of MED28 on HBP1 and E-cadherin and inactivate the Wnt/β-catenin pathway in colorectal cancer, suggesting a protective effect of ATRA against colorectal cancer. J. Cell. Physiol. 231: 1796-1803, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660958

  11. CX3CL1(+ Microparticles Mediate the Chemoattraction of Alveolar Macrophages toward Apoptotic Acute Promyelocytic Leukemic Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hui Tsai

    2014-02-01

    Full Text Available Background/Aims: During the resolution phase of inflammation, release of “find-me” signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4 cells. Methods/Results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+ apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. Conclusion: CX3CL1(+ apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

  12. Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with all-trans retinoic acid (ATRA), trichostatin A (TSA) or ATRA combined with TSA. Methods: After the induction with ATRA, TSA, or ATRA combined with TSA in different concentrations for 96 h, the iodine uptake of FTC-133 cells was observed. The concentrations for different groups were as follows: ATRA 1.0 ×10-6 mol/L(Alow group), ATRA 1.0 × 10-4 mol/L (Ahigh group), TSA 1.65 ×10-7 mol/L (T group), Alow + T group, Ahigh + T group and ethanol (control group). Cell quantities and morphology were observed by HE staining. FTC-133 cells were subcutaneously injected into nude mice. Twelve nude mice were randomly divided into 4 groups after tumor formation: ATRA group (2 mg/kg, intragastric administration), TSA group (10 mg/kg, intraperitoneal injection), combined therapy group (ATRA + TSA, the same doses as above) and saline control group (10 ml/kg, intragastric and intraperitoneal administration, respectively). Drugs were administered to the tumor-bearing mice according to the mouse body mass daily. At the 22nd day, the tumor-bearing mice were injected with 37 MBq 131I intraperitoneally. The biodistribution of 131I and gamma imaging were performed at 4, 6, 12 and 24 h after the injection respectively. Histopathological examinations of the tumor samples were taken after imaging completion. The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0. Results: The cellular iodine uptake were (23 885 ± 616.0) and (13 849 ±728.2) counts · min-1 · 10-6 cells in the Alow + T group and Ahigh + T group respectively, and the data were (985 ± 84.2) - (17 600 ± 782.7) counts · min-1 · 10-6 in the other groups (F=600.879, P<0.001). The % ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h. The % ID/g of

  13. AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells.

    Science.gov (United States)

    Gianní, M; Li Calzi, M; Terao, M; Guiso, G; Caccia, S; Barbui, T; Rambaldi, A; Garattini, E

    1996-02-15

    All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto

  14. Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

    Science.gov (United States)

    Topletz, Ariel R.; Tripathy, Sasmita; Foti, Robert S.; Shimshoni, Jakob A.; Nelson, Wendel L.

    2015-01-01

    All-trans-retinoic acid (atRA), the active metabolite of vitamin A, induces gene transcription via binding to nuclear retinoic acid receptors (RARs). The primary hydroxylated metabolites formed from atRA by CYP26A1, and the subsequent metabolite 4-oxo-atRA, bind to RARs and potentially have biologic activity. Hence, CYP26A1, the main atRA hydroxylase, may function either to deplete bioactive retinoids or to form active metabolites. This study aimed to determine the role of CYP26A1 in modulating RAR activation via formation and elimination of active retinoids. After treatment of HepG2 cells with atRA, (4S)-OH-atRA, (4R)-OH-atRA, 4-oxo-atRA, and 18-OH-atRA, mRNAs of CYP26A1 and RARβ were increased 300- to 3000-fold, with 4-oxo-atRA and atRA being the most potent inducers. However, >60% of the 4-OH-atRA enantiomers were converted to 4-oxo-atRA in the first 12 hours of treatment, suggesting that the activity of the 4-OH-atRA was due to 4-oxo-atRA. In human hepatocytes, atRA, 4-OH-atRA, and 4-oxo-atRA induced CYP26A1 and 4-oxo-atRA formation was observed from 4-OH-atRA. In HepG2 cells, 4-oxo-atRA formation was observed even in the absence of CYP26A1 activity and this formation was not inhibited by ketoconazole. In human liver microsomes, 4-oxo-atRA formation was supported by NAD+, suggesting that 4-oxo-atRA formation is mediated by a microsomal alcohol dehydrogenase. Although 4-oxo-atRA was not formed by CYP26A1, it was depleted by CYP26A1 (Km = 63 nM and intrinsic clearance = 90 μl/min per pmol). Similarly, CYP26A1 depleted 18-OH-atRA and the 4-OH-atRA enantiomers. These data support the role of CYP26A1 to clear bioactive retinoids, and suggest that the enzyme forming active 4-oxo-atRA may be important in modulating retinoid action. PMID:25492813

  15. Subsidized optimal ART for HIV-positive temporary residents of Australia improves virological outcomes: results from the Australian HIV Observational Database Temporary Residents Access Study

    Directory of Open Access Journals (Sweden)

    Kathy Petoumenos

    2015-02-01

    Full Text Available Introduction: HIV-positive (HIV+ temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD Temporary Residents Access Study (ATRAS and to determine the short- and long-term outcomes of receiving (subsidized optimal ART and the impact on onwards HIV transmission. Methods: ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD and the proportion with undetectable (<50 copies/ml HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load. Results: A total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml and the median CD4 cell count was 343 cells/µl (IQR: 222–479. At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load. Conclusions: The

  16. Effects of all-trans-retinoic add on chemotherapeutics sensibility and Survivin gene expression of human colon cancer LoVo cell line%全反式维甲酸对人结肠癌LoVo细胞化疗药物敏感性及Survivin基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    胡宝光; 郑宗珩; 卫洪波; 韩晓燕; 魏波; 黄江龙

    2011-01-01

    Objective To study the effects of all-trans-retinoic acid (ATRA) on chemotherapeutics sensibility and expression of Survivin in human LoVo colon cancer cell line, and to provide a theoretical basis for clinical application of ATRA.Methods Flow cytometer (FCM) was used to detect the cell cycle of LoVo colon cancer cell line after treated with various dose of ATRA (10-5 mol/L, 10-6 mol/L and 10-7 mol/L)for 24 h, 48 h, 72 h, 5 d, 9 d and 15 d respectively.The cells were divided into ATRA group (10-6 mol/L)and control group (cultured in routine medium RPMI1640).Meanwhile, each group were divided into subgroups respectively treated with 0 g/L, 2 g/L, 4 g/L and 6 g/L 5-fluorouracil(5-FU) , or with 0 mg/L, 200 mg/L, 400 mg/L and 600 mg/L mitomycin (MMC).MTT assay was used to detect the viability of cells so as to analyze the change in chemotherapeutics sensibility.Drug interactions were analyzed according to the interaction effects.Staining with acridine orange (AO) and ethidium bromide (EB) was used to study the apoptosis in control group(RPMI1640) , ATRA group (10-6 mol/L), 5-FU group (4 g/L), MMC group (400 mg/L), ATRA (10-6 mol/L) + 5-FU (4 g/L) group and ATRA (10-6 mol/L) + MMC (400 mg/L) group.The expression of Survivin in the LoVo cell line was investigated by immunofluorescence technique.Results Compared with the control group, the percentage of cell in Go-G1 phase increased after interference with various doses of ATRA for 24 hours, peaked at 48 h, and gradually decreased afterwards, while the percentage of cells in stages S and G2-M decreased, reach the trough at 48 h, and then increased gradually.Effects of 10-6 mol/L ATRA were most significant at all time spots.Compared with control group, 10-6 mol/L ATRA reduced cell survival rate (P<0.05),and the survival rates in control subgroups treated with various doses of 5-FU were significantly higher than those in ATRA group (all P<0.05).In MMC-treated control group, cell survival rate with 200 mg/L MMC was lower

  17. Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy.

    Science.gov (United States)

    Wu, Wei; Lin, Yan; Xiang, Lili; Dong, Weimin; Hua, Xiaoying; Ling, Yun; Li, Haiqian; Yan, Feng; Xie, Xiaobao; Gu, Weiying

    2016-06-01

    In our previous in vitro trials, decitabine and all-trans retinoic acid (ATRA) demonstrated synergistic effects on growth inhibition, differentiation, and apoptosis in SHI-1 cells; in K562 cells, ATRA enhanced the effect of decitabine on p16 demethylation, and the combination of the two drugs was found to activate RAR-β expression (p16 and RAR-β are two tumor suppressor genes). On the rationale of our in vitro trials, we used low-dose decitabine and ATRA to treat 31 myeloid neoplasms deemed ineligible for intensive chemotherapy. The regimen consisted of decitabine at the dose of 15 mg/m(2) intravenously over 1 h daily for consecutive 5 days and ATRA at the dose of 20 mg/m(2) orally from day 1 to 28 except day 4 to 28 in the first cycle, and the regimen was repeated every 28 days. After 6 cycles, decitabine treatment was stopped, and ATRA treatment was continued for maintenance treatment. Treated with a median of 2 cycles (range 1-6), 7 patients (22.6 %) achieved complete remission (CR), 7 (22.6 %) marrow CR (mCR), and 4 (12.9 %) partial remission (PR). The overall remission (CR, mCR, and PR) rate was 58.1 %, and the best response (CR and mCR) rate was 45.2 %. The median overall survival (OS) was 11.0 months, the 1-year OS rate was 41.9 %, and the 2-year OS rate was 26.6 %. In univariate analyses, age, performance status, comorbidities, white blood cell counts and platelets at diagnosis, percentage of bone marrow blasts, karyotype, and treatment efficacy demonstrated no impacts on OS (P > 0.05, each). Main side effects were tolerable hematologic toxicities. In conclusion, low-dose decitabine plus ATRA is a promising treatment for patients with myeloid neoplasms judged ineligible for intensive chemotherapy.

  18. 全反式维A酸对UVB照射的A375细胞酪氨酸酶代谢及铜锌超氧化物歧化酶的影响%Effects of all-trans retinoic ac id on tyrosinase metabolism and Cu/Zn superoxide dismutase mRNA expression in A375 cells irradiated by ultraviolet B

    Institute of Scientific and Technical Information of China (English)

    蒋帅; 魏大鹏; 罗志娟; 陈菊萍

    2012-01-01

    Objective To evaluate the effects of all-trans retinoic acid (ATRA) on melanin content,activity and protein expression of tyrosinase,mRNA expression of Cu/Zn superoxide dismutase (SOD) in A375 cells irradiated with ultraviolet B (UVB).Methods Cultured A375 cells were classified into 6 groups:ATRA+UVB group treated with ATRA after UVB irradiation,hydroquinone+UVB group treated with hydroquinone after UVB irradiation,UVB group and ATRA group treated with UVB irradiation and ATRA respectively,negative control group receiving no treatment.Melanin content and tyrosinase activity were determined by NaOH solubilization assay and dopa-oxidation assay respectively at 24,48 and 72 hours after the addition of ATRA into medium.Western blot was performed to detect the protein expression of tyrosinase,and real-time quantitative PCR to measure the mRNA expressions of tyrosinase and Cu/Zn SOD in A375 cells after 24-hour culture with ATRA.Results The melanin content and tyrosinase activity decreased in UVB-irradiated cells after being treated with ATRA for 24,48 and 72 hours.The protein (gray scale) and mRNA (2-△△Ct value) expression levels of tyrosinase were 0.72 ± 0.070 and 1.400 ± 0.135 respectively at 24 hours after UVB irradiation,decreased to 0.42 ± 0.056 (P <0.01) and 0.810 ± 0.062 (P < 0.01 ) respectively after additional treatment with ATRA.The mRNA expression level of Cu/Zn SOD was 0.323 ± 0.066 in A375 cells at 24 hours after UVB irradiation,and increased to 0.625 ±0.103 (P < 0.01 ) after additional treatment with ATRA.Conclusion ATRA can suppress UVB-induced increase in melanin synthesis and elevate Cu/Zn SOD level in A375 cells,likely through tyrosinase pathway.%目的 探讨全反式维A酸(ATRA)对中波紫外线(UVB)照射的人A375黑素瘤株细胞黑素含量、酪氨酸酶及铜锌超氧化物歧化酶(Cu/ZnSOD)的影响.方法 将培养的A375细胞分为6组:ATRA+UVB组:A375细胞照射UVB后加入全反式维A酸;氢醌+UVB组:照射UVB后

  19. Limited selection of sodium channel blocking toxin-producing bacteria from paralytic shellfish toxin-contaminated mussels (Aulacomya ater).

    Science.gov (United States)

    Vásquez, Mónica; Grüttner, Carol; Möeller, Blanca; Moore, Edward R B

    2002-01-01

    Paralytic shellfish toxins (PSTs) are sodium channel blocking (SCB) toxins, produced by cyanobacteria, as well as by marine dinoflagellates and their associated bacteria, and cause serious health and economic concern worldwide. In a previous study, approximately 70% of the bacteria enriched from PST-contaminated shellfish tissue and isolated on marine agar medium were observed to produce SCB toxins. In the study reported here, the high percentage of cultivable toxigenic bacteria is demonstrated to be obtained through a marked selection on marine agar medium. The cultivable as well as the total bacterial diversity associated with PST-contaminated shellfish collected from the Magallanes region in the south of Chile has been analysed. Approximately 80% of bacterial isolates, analysed by restriction analysis of PCR amplified ribosomal DNA (i.e., ARDRA fingerprinting), were limited to only two genotypic OTUs (operational taxonomic unit). Sequence determination and analysis of the 16S rDNA from representative isolates of both OTUs established them to be closely related to species of the Psychrobacter genus of the gamma-subclass of the Proteobacteria. The total bacterial diversity in the shellfish was further analysed, using a cultivation-independent strategy of extraction of total DNA from contaminated tissue, PCR-amplification of bacterial 16S rRNA genes, cloning of the PCR products and analysis of the cloned 16S rDNA sequence types by fingerprinting and sequencing. Only 2% of the cloned sequence types corresponded to species of the Psychrobacter genus. The 16S rDNA sequence types detected clustered with species of the y-Proteobacteria subclass, the Cytophaga-Flexibacter-Bacteroides (CFB), the Fusobacteria and the Firmicutes phyla. The level of diversity observed within the libraries of cloned 16S rDNA was markedly greater than that observed among isolates obtained through marine agar enrichment cultures from the same shellfish tissue. Additionally the predominant cloned 16S rDNA sequence types detected from samples of the surrounding seawater demonstrated no correlation with those observed in the PST-contaminated mussels. PMID:12238500

  20. RAI,one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    王雪皎; 张睿; 刘芝华; 王秀琴; 丁芳; 郭明洲; 吴旻

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  1. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  2. Differentiation of stem cells upon deprivation of exogenous FGF2

    DEFF Research Database (Denmark)

    Kjartansdóttir, Kristín Rós; Gabrielsen, Anette; Reda, Ahmed;

    2012-01-01

    Establishing a model for in vitro differentiation of human embryonic stem cells (hESCs) towards the germ cell lineage could be used to identify molecular mechanisms behind germ cell differentiation that may help in understanding human infertility. Here, we evaluate whether a lack of exogenous...... fibroblast growth factor 2 (FGF2) is supporting spontaneous differentiation of hESCs cultured on human foreskin fibroblast (hFF) monolayers towards germ cell lineage. Additionally to depriving the hESCs of exogenous FGF2, cells were stimulated with all-trans retinoic acid (ATRA). To get a more comprehensive...... impression on effects of removal of FGF2 and stimulation with ATRA, we combined the results of three cell lines for each experimental setting. When combining gene expression profiles of three cell lines for 96 genes, only 6 genes showed a significant up-regulation in all cell lines, when no FGF2 was added...

  3. Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver.

    Science.gov (United States)

    Qian, Linxi; Zolfaghari, Reza; Ross, A Catharine

    2010-07-01

    Several cytochrome P450 (CYP) enzymes catalyze the C4-hydroxylation of retinoic acid (RA), a potent inducer of cell differentiation and an agent in the treatment of several diseases. Here, we have characterized CYP2C22, a member of the rat CYP2C family with homology to human CYP2C8 and CYP2C9. CYP2C22 was expressed nearly exclusively in hepatocytes, where it was one of the more abundant mRNAs transcripts. In H-4-II-E rat hepatoma cells, CYP2C22 mRNA was upregulated by all-trans (at)-RA, and Am580, a nonmetabolizable analog of at-RA. In comparison, in primary human hepatocytes, at-RA increased CYP2C9 but not CYP2C8 mRNA. Analysis of the CYP2C22 promoter region revealed a RA response element (5'-GGTTCA-(n)5-AGGTCA-3') in the distal flanking region, which bound the nuclear hormone receptors RAR and RXR and which was required for transcriptional activation response of this promoter to RA in CYP2C22-luciferase-transfected RA-treated HepG2 cells. The cDNA-expressed CYP2C22 protein metabolized [3H]at-RA to more polar metabolites. While long-chain polyunsaturated fatty acids competed, 9-cis-RA was a stronger competitor. Our studies demonstrate that CYP2C22 is a high-abundance, retinoid-inducible, hepatic P450 with the potential to metabolize at-RA, providing additional insight into the role of the CYP2C gene family in retinoid homeostasis.

  4. BCL-xL/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells.

    Science.gov (United States)

    Perri, Mariarita; Yap, Jeremy L; Yu, Jianshi; Cione, Erika; Fletcher, Steven; Kane, Maureen A

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia-retinoic acid receptor, alpha fusion protein (PML-RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates > 80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As2O3 has increased survival further, patients that experience relapse and are refractory to atRA and/or As2O3 is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-xL) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-xL/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment.

  5. PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes.

    Directory of Open Access Journals (Sweden)

    Saravanan Kanakasabai

    Full Text Available Neural stem cells (NSCs are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS. Peroxisome proliferator-activated receptor gamma (PPARγ is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture. We found that in vitro culture of mouse NSCs in neurobasal medium with B27 in the presence of epidermal growth factor (EGF and basic fibroblast growth factor (bFGF induced their growth and expansion as neurospheres. Addition of all-trans retinoic acid (ATRA and PPARγ agonist ciglitazone or 15-Deoxy-Δ(12,14-Prostaglandin J(2 (15d-PGJ2 resulted in a dose-dependent inhibition of cell viability and proliferation of NSCs in culture. Interestingly, NSCs cultured with PPARγ agonists, but not ATRA, showed significant increase in oligodendrocyte precursor-specific O4 and NG2 reactivity with a reduction in NSC marker nestin, in 3-7 days. In vitro treatment with PPARγ agonists and ATRA also induced modest increase in the expression of neuronal β-III tubulin and astrocyte-specific GFAP in NSCs in 3-7 days. Further analyses showed that PPARγ agonists and ATRA induced significant alterations in the expression of many stemness and differentiation genes associated with neuro-glial differentiation in NSCs. These findings highlight the influence of PPARγ agonists in promoting neuro-glial differentiation of NSCs and its significance in the treatment of neurodegenerative diseases.

  6. Ascosphaera subglobosa, a new spore cyst fungus from North America associated with the solitary bee Megachile rotundata.

    Science.gov (United States)

    Wynns, Anja Amtoft; Jensen, Annette Bruun; Eilenberg, Jørgen; James, Rosalind

    2012-01-01

    Ascosphaera subglobosa (Eurotiomycetes: Onygenales) is newly described from the pollen provisions and nesting material of the solitary leaf-cutting bee Megachile rotundata in Canada and the western United States. This new species, related to A. atra and A. duoformis, is distinguished from other Ascosphaera species by its globose to subglobose ascospores, evanescent spore balls and unique nuclear ribosomal DNA sequences (ITS and LSU). PMID:21828215

  7. Retinoic Acid Drives Aryl Hydrocarbon Receptor Expression and Is Instrumental to Dioxin-Induced Toxicity during Palate Development

    OpenAIRE

    Jacobs, Hugues; Dennefeld, Christine; Féret, Betty; Viluksela, Matti; Håkansson, Helen; Mark, Manuel; Ghyselinck, Norbert B.

    2011-01-01

    Background: Palate development depends on complex events and is very sensitive to disruption. Accordingly, clefts are the most common congenital malformations worldwide, and a connection is proposed with fetal exposure to toxic factors or environmental contaminants, such as dioxins. There is increasing evidence that dioxin interferes with all-trans-retinoic acid (atRA), a hormone-like signal derived from vitamin A, which plays an essential role during embryonic development. Although similarit...

  8. The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells

    Energy Technology Data Exchange (ETDEWEB)

    Marzinke, Mark A. [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Clagett-Dame, Margaret, E-mail: dame@biochem.wisc.edu [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Pharmaceutical Science Division, University of Wisconsin-Madison, Madison, WI 53705-2222 (United States)

    2012-01-01

    The vitamin A metabolite all-trans retinoic acid (atRA) functions in nervous system development and regulates cell proliferation and differentiation. Neuroblastoma cells (SH-SY5Y and Neuro2a or N2A) exposed to atRA undergo growth inhibition and neuronal differentiation, both of which are preceded by an increase in Clmn mRNA. Treatment of N2A cells with atRA produces a reduction in phosphohistone 3 immunostaining and BrdU incorporation, both indicators of a reduction in cell proliferation. These effects are nearly eliminated in atRA-treated shClmn knockdown cells. Loss of Clmn in the mouse N2A cell line also results in a significant reduction of atRA-mediated neurite outgrowth, a response that can be rescued by reintroduction of the Clmn sequence. In contrast, ectopic overexpression of Clmn produces an increase in the cyclin dependent kinase inhibitor, p21{sup Cip1}, a decrease in cyclin D1 protein and an increase in hypophosphorylated Rb, showing that Clmn participates in G{sub 1}/S arrest. Clmn overexpression alone is sufficient to inhibit N2A cell proliferation, whereas both Clmn and atRA must be present to induce neurite outgrowth. This study shows that the atRA-responsive gene Clmn promotes exit from the cell cycle, a requisite event for neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer Calmin is a retinoic acid-responsive gene. Black-Right-Pointing-Pointer Calmin promotes cell cycle exit in N2A cells. Black-Right-Pointing-Pointer Calmin overexpression increases p21Cip1 and decreases cyclin D1. Black-Right-Pointing-Pointer Calmin is required for RA-induced growth inhibition and neurite outgrowth.

  9. Herbo-mineral ayurvedic treatment in a high risk acute promyelocytic leukemia patient with second relapse: 12 years follow up

    OpenAIRE

    Balendu Prakash; Parikh, Purvish M; Sanjoy K Pal

    2010-01-01

    A 47 year old diabetic male patient was diagnosed and treated for high risk AML-M3 at Tata Memorial Hospital (BJ 17572), Mumbai in September 1995. His bone marrow aspiration cytology indicated 96% promyelocytes with abnormal forms, absence of lymphocytic series and myeloperoxide test 100% positive. Initially treated with ATRA, he achieved hematological remission on day 60, but cytogenetically the disease persisted. The patient received induction and consolidated chemotherapy with Daunorubicin...

  10. Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

    Directory of Open Access Journals (Sweden)

    Jing-Bo Peng

    2014-01-01

    Full Text Available A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA in human plasma. Acitretin was used as the internal standard (IS. After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE, ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999 with a lower limit of quantitation (LLOQ of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers.

  11. Inorganic Carbon Turnover caused by Digestion of Carbonate Sands and Metabolic Activity of Holothurians

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Kenneth; Silverman, Jacob; Kravitz, Benjamin S.; Rivlin, Tanya; Schneider-Mor, Aya; Barbosa, Sergio; Byrne, Maria; Caldeira, Ken

    2013-11-20

    Recent measurements have shown that holothurians (sea cucumbers) play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this study inorganic additional aspects of carbon turnover were determined in laboratory incubations of Holothuria atra, H. leucospilota and Stichopus herrmanni from One Tree Reef, Great Barrier Reef. The pH values of the gut lumen ranged from 6.1 to 6.7 in animals with empty digestive tracts as opposed to 7.0 to 7.6 when digestive tracts were filled with sediment. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni of 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state for both aragonite and calcite minerals during laboratory incubations decreased markedly due to a greater increase in dissolved inorganic carbon (DIC) relative to total alkalinity (AT) as a result of respiration by the animals. Our results support the hypothesis that deposit feeders such as sea cucumbers play an important ecological role in the coral reef CaCO3 cycle.

  12. Microstructural examination of V–(Fe or Cr)–Ti alloys after thermal-creep or irradiation-creep tests

    OpenAIRE

    Fukumoto, K.; Takahashi, S.; KURTZ, R.J.; Smith, D. L.; Matsui, H

    2005-01-01

    Microstructural examinations have been performed on irradiation-creep and thermal-creep pressurized tube specimensof V–3Fe–4Ti–0.1Si in order to understand failure and creep mechanisms. There are no typical microstructuraldifferences between unstressed and pressurized creep tube specimens irradiated in ATR-A1 in the irradiation temperatureregime from 212 to 300 ℃. Failed thermal creep specimens show dislocation structures dependent on the tubespecimen geometry. This can be interpreted in term...

  13. Una interpretación numérica de la crónica de Huamán Poma de Ayala

    Directory of Open Access Journals (Sweden)

    Marcín Mróz

    1984-12-01

    Full Text Available Retoma de uno de los temas que ha atraído especial atención de distintos estudiosos siguiendo una línea de análisis iniciada por Juan Ossio en su tesis de 1970. El autor del presente artículo realiza una interpretación numérica de las edades de la humanidad según el gran cronista indio.

  14. A Novel mTORC1-Dependent, Akt-Independent Pathway Differentiates the Gut Tropism of Regulatory and Conventional CD4 T Cells.

    Science.gov (United States)

    Chen, Leo C; Nicholson, Yawah T; Rosborough, Brian R; Thomson, Angus W; Raimondi, Giorgio

    2016-08-15

    The vitamin A metabolite all-trans retinoic acid (ATRA) induces a gut-homing phenotype in activated CD4(+) conventional T cells (Tconv) by upregulating the integrin α4β7 and the chemokine receptor CCR9. We report that, in contrast to mouse Tconv, only ∼50% of regulatory T cells (Treg) upregulate CCR9 when stimulated by physiological levels of ATRA, even though Tconv and Treg express similar levels of the retinoic acid receptor (RAR). The resulting bimodal CCR9 expression is not associated with differences in the extent of their proliferation, level of Foxp3 expression, or affiliation with naturally occurring Treg or induced Treg in the circulating Treg pool. Furthermore, we find that exposure of Treg to the mechanistic target of rapamycin (mTOR) inhibitor rapamycin suppresses upregulation of both CCR9 and α4β7, an effect that is not evident with Tconv. This suggests that in Treg, ATRA-induced upregulation of CCR9 and α4β7 is dependent on activation of a mTOR signaling pathway. The involvement of mTOR is independent of Akt activity, because specific inhibition of Akt, pyruvate dehydrogenase kinase-1, or its downstream target glycogen synthase kinase-3 did not prevent CCR9 expression. Additionally, Rictor (mTOR complex [mTORC]2)-deficient Treg showed unaltered ability to express CCR9, whereas Raptor (mTORC1)-deficient Treg were unable to upregulate CCR9, suggesting the selective participation of mTORC1. These findings reveal a novel difference between ATRA signaling and chemokine receptor induction in Treg versus Tconv and provide a framework via which the migratory behavior of Treg versus Tconv might be regulated differentially for therapeutic purposes. PMID:27402696

  15. CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities

    OpenAIRE

    Lee, Young-jin; Jones, Letetia C.; Timchenko, Nikolai A.; Perrotti, Danilo; Tenen, Daniel G; Kogan, Scott C.

    2006-01-01

    CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them...

  16. Aproximaci??n a la s??ntesis de aureol, un meroterpeno bioactivo de origen marino

    OpenAIRE

    Rivas Basc??n, Nazaret

    2013-01-01

    El desarrollo de metodolog??as de s??ntesis sostenibles y eficientes hacia compuestos org??nicos con interesantes propiedades biol??gicas ha atra??do la atenci??n de los grupos de investigaci??n dedicados a la s??ntesis org??nica.1 En este contexto hemos abordado una aproximaci??n sint??tica hacia aureol mediante una metodolog??a de s??ntesis eficiente y compatible con el medio ambiente.

  17. Retinoic Acid Inhibits Airway Smooth Muscle Cell Migration

    OpenAIRE

    Day, Regina M.; Lee, Young H.; Park, Ah-Mee; Suzuki, Yuichiro J.

    2006-01-01

    Airway remodeling in chronic asthma is characterized by increased smooth muscle mass that is associated with the reduction of the bronchial lumen as well as airway hyperresponsiveness. The development of agents that inhibit smooth muscle growth is therefore of interest for therapy to prevent asthma-associated airway remodeling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth muscle cells (SMCs) from the systemic and pulmonary circulation. The present study investigated the...

  18. Retinoic Acid Biosynthesis Is Impaired in Human and Murine Endometriosis1

    OpenAIRE

    Pierzchalski, Keely; Taylor, Robert N.; Nezhat, Ceana; Jones, Jace W.; Napoli, Joseph L.; Yang, Guixiang; Kane, Maureen A.; Sidell, Neil

    2014-01-01

    Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-...

  19. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  20. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  1. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Marumi; Ikenaka, Yoshinori [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan); Ishizuka, Mayumi, E-mail: ishizum@vetmed.hokudai.ac.jp [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. Black-Right-Pointing-Pointer We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. Black-Right-Pointing-Pointer RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. Black-Right-Pointing-Pointer It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RAR{alpha}. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1-100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  2. The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

    Directory of Open Access Journals (Sweden)

    Rosier Randy N

    2004-03-01

    Full Text Available Abstract Background Nuclear factor kappa B (NFκB is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs. Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA and the pan-RAR antagonist, AGN193109. Results At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9 and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1, in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. Conclusion We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids.

  3. HEMOPOIETIC SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    2006261 Enhancement of all - trans retinoic acid -induced differentiation by bufalin in primary culture of acute promyelocytic leukmia cells. ZHOU Zhitu (周志图),et al. Dept Med Oncol, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Intern Med 2006; 45(4):314-317. Objective:To investigate the effect of bufalin combined with all -trans retinoic acid induced (ATRA) differentiation of acute promyelocytic leukemia ( API) cells

  4. Evolution of a FLT3-TKD mutated subclone at meningeal relapse in acute promyelocytic leukemia.

    Science.gov (United States)

    Bochtler, Tilmann; Fröhling, Stefan; Weichert, Wilko; Endris, Volker; Thiede, Christian; Hutter, Barbara; Hundemer, Michael; Ho, Anthony D; Krämer, Alwin

    2016-09-01

    Here, we report the case of an acute promyelocytic leukemia (APL) patient who-although negative for FLT3 mutations at diagnosis-developed isolated FLT3 tyrosine kinase II domain (FLT3-TKD)-positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-yr-old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA (ATRA plus idarubicin) protocol. Thirteen months after the start of ATRA maintenance, the patient suffered clinically overt meningeal relapse along with minute molecular traces of PML/RARA (promyelocytic leukemia/retinoic acid receptor alpha) in the bone marrow. Following treatment with arsenic trioxide and ATRA in combination with intrathecal cytarabine and methotrexate, the patient achieved a complete molecular remission in both cerebrospinal fluid (CSF) and bone marrow, which currently lasts for 2 yr after completion of therapy. Whole-exome sequencing and subsequent ultradeep targeted resequencing revealed a heterozygous FLT3-TKD mutation in CSF leukemic cells (p.D835Y, c.2503G>T, 1000/1961 reads [51%]), which was undetectable in the concurrent bone marrow sample. Interestingly, the FLT3-TKD mutated meningeal clone originated from a small bone marrow subclone present in a variant allele frequency of 0.4% (6/1553 reads) at initial diagnosis. This case highlights the concept of clonal evolution with a subclone harboring an additional mutation being selected as the "fittest" and leading to meningeal relapse. It also further supports earlier suggestions that FLT3 mutations may play a role for migration and clonal expansion in the CSF sanctuary site. PMID:27626069

  5. Lutzomyia gasparviannai Martins, Godoy & Silva, 1962, probable vector of Leishmania mexicana ssp. in Viana municipality, Espírito Santo State, Brazil

    Directory of Open Access Journals (Sweden)

    Aloísio Falqueto

    1985-12-01

    Full Text Available Dos flebótomos atraídos pelo Proechimys iheringi numa área onde esse roedor foi achado naturalmente infectado por Leishmania mexicana ssp., 98,1% foram Lutzomyia gasparviannai, o que sugere que essa espécie não antropofílica seja o transmissor entre os roedores mas não habitualmente ao homem.

  6. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    OpenAIRE

    Zhenya Gao; Lijun Huo; Dongmei Cui; Xiao Yang; Junwen Zeng

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cu...

  7. Thermal conditions during juvenile development affect adult dispersal in a spider

    OpenAIRE

    Bonte, Dries; Travis, Justin M. J.; Clercq, Nele De; Zwertvaegher, Ingrid; Lens, Luc

    2008-01-01

    Abstract: Understanding the causes and consequences of dispersal is a prerequisite for the effective management of natural populations. Rather than treating dispersal as a fixed trait, it should be considered a plastic process that responds to both genetic and environmental conditions. Here, we consider how the ambient temperature experienced by juvenile Erigone atra, a spider inhabiting crop habitat, influences adult dispersal. This species exhibits 2 distinct forms of dispersal, ballooning ...

  8. Retinoid- and sodium-butyrate– induced decrease in heat shock protein 70 membrane-positive tumor cells is associated with reduced sensitivity to natural killer cell lysis, growth delay, and altered growth morphology

    OpenAIRE

    Gehrmann, Mathias; Schönberger, Johann; Zilch, Tanja; Rossbacher, Lydia; Thonigs, Gerald; Eilles, Christoph; Multhoff, Gabriele

    2005-01-01

    Human tumors frequently present heat shock protein 70 (Hsp70) on their cell membranes, whereas corresponding normal tissues fail to do so. Therefore, an Hsp70 membrane-positive phenotype provided a tumor-specific marker. Moreover, membrane-bound Hsp70 provides a target structure for the cytolytic attack mediated by natural killer (NK) cells. Vitamin A derivatives 13-cis retinoic acid (13-RA) and all-trans retinoic acid (ATRA) and sodium-butyrate (SBU) are known for their redifferentiating cap...

  9. Radular marks produced by grazing gastropods of the rocky intertidal

    Directory of Open Access Journals (Sweden)

    Yván Reyes

    2014-06-01

    Full Text Available We had used artificial surfaces to examine the radular marks of four common grazing gastropods from Ancon Bay. In this work we show radular marks on dental wax surface of the trochid Tegula atra (Lesson, 1830, the fissurellid Fissurella peruviana Lamarck, 1822, the lottid Lottia ceciliana (Orbigny, 1841 and the littorinid Nodilittorina peruviana (Lamarck, 1822. In addition, the radular type is described to each species to relate it to the produced mark.

  10. Retinoid-dependent growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia cells. Expression and activation of caspases.

    Science.gov (United States)

    Gianni, M; Ponzanelli, I; Mologni, L; Reichert, U; Rambaldi, A; Terao, M; Garattini, E

    2000-05-01

    In the NB4 model of acute promyelocytic leukemia (APL), ATRA, 9-cis retinoic acid (9-cis RA), the pan-RAR and RARalpha-selective agonists, TTNPB and AM580, induce growth inhibition, granulocytic differentiation and apoptosis. By contrast, two RXR agonists, a RARbeta agonist and an anti-AP1 retinoid have very limited activity, ATRA- and AM580-dependent effects are completely inhibited by RAR antagonistic blockade, while 9-cis RA-induced cell-growth-inhibition and apoptosis are equally inhibited by RAR and RXR antagonists. ATRA, 9-cis RA and AM580 cause upregulation of the mRNAs coding for pro-caspase-1, -7, -8, and -9, which, however, results in increased synthesis of only pro-caspase-1 and -7 proteins. These phenomena are associated with activation of pro-caspase-6, -7 and -8, cytochrome c release from the mitochondria, inversion of Bcl-2/Bax ratio and degradation of PML-RARalpha. Caspase activation is fundamental for retinoid-induced apoptosis, which is suppressed by the caspase-inhibitor z-VAD.

  11. The Retinoic Acid Receptor-α mediates human T-cell activation and Th2 cytokine and chemokine production

    Directory of Open Access Journals (Sweden)

    Key Michael

    2008-04-01

    Full Text Available Abstract Background We have recently demonstrated that all-trans-retinoic acid (ATRA and 9-cis-retinoic acid (9-cis RA promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-γ and TNF-α expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA, and the retinoic acid receptor-α (RAR-α-selective agonist, AM580 but not with the RAR-β/γ ligand, 4-hydroxyphenylretinamide (4-HPR. Results The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-α-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-α-selective antagonist, RO 41–5253, inhibited these effects. Conclusion These results strongly support a role for RAR-α engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

  12. Effects of synthetic retinoids and retinoic acid isomers on the expression of alkaline phosphatase in F9 teratocarcinoma cells.

    Science.gov (United States)

    Gianni, M; Zanotta, S; Terao, M; Garattini, S; Garattini, E

    1993-10-15

    Expression of ALP in F9 teratocarcinoma cells is induced by all-trans retinoic acid (ATRA) (Gianni' et al., Biochem. J. 274: 673-678, 1991). The specific ligand for retinoic acid related receptors (RXRs), 9-cis retinoic acid (9-cis RA), and three synthetic analogs binding to the alpha, beta and gamma forms of the retinoic acid receptors (RARs), AM580, CD2019, and CD437, were used to study their effects on alkaline phosphatase (ALP) enzymatic activity and mRNA levels. At concentrations close to the Kd for their respective receptors, 9-cis RA, AM580 (the RAR alpha agonist) and CD437 (the RAR gamma agonist) clearly upregulate the expression of the ALP gene, whereas the effect of CD2019 (the RAR beta agonist) is very modest. A specific inhibitor of the RAR alpha, Ro 41-5253, completely blocks the induction of ALP triggered by AM580, while it has minor effects on the upregulation caused by ATRA, 9-cis RA, CD437 and CD2019. The induction of ALP observed with the various retinoids is inhibited by the contemporaneous treatment with dibutyryl cAMP. The levels of the RAR alpha and gamma transcripts are unaltered, while RAR beta mRNAs are induced by ATRA, AM580, CD437 and to a lower extent by 9-cis RA and CD2019.

  13. Tn5-mutagenesis and identification of atr operon and trpE gene responsible for indole-3-acetic acid synthesis in Azospirillum brasilense Yu62

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To bring more information about synthesis of indole-3-acetic acid (IAA) from Azospirillum brasilense, a Tn5-insertion library of A. brasilense Yu62 was constructed and subjected to screening for IAA producing mutants. Two mutants with decreased IAA levels, named as A3 and A24, were isolated. The sequence analysis of loci tagged showed that the Tn5-1063a was located in the atrA gene encoding GntR family transcriptional regulator and trpE gene encoding component I of anthranilate synthase respectively. At the same time, atrB encoding phosphotransferase and atrC encoding aminotransferase were cloned downstream the atrA gene and atrA,atrB and atrC were clustered in an operon. Mutagenesis and complementation studies showed that atrA and atrC were involved in IAA synthesis. IAA levels of trpE mutant and wild-type strain could be improved by adding anthranilate into the medium.

  14. Role of retinoids in the prevention and treatment of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Catherine; C; Applegate; Michelle; A; Lane

    2015-01-01

    Vitamin A and its derivatives, retinoids, have been widely studied for their use as cancer chemotherapeutic agents. With respect to colorectal cancer(CRC), several critical mutations dysregulate pathways implicated in progression and metastasis, resulting in aberrant Wnt/β-catenin signaling, gain-of-function mutations in K-ras and phosphatidylinositol-3-kinase/Akt, cyclooxygenase-2 over-expression, reduction of peroxisome proliferatoractivated receptor γ activation, and loss of p53 function. Dysregulation leads to increased cellular proliferation and invasion and decreased cell-cell interaction and differentiation. Retinoids affect these pathways by various mechanisms, many involving retinoic acid receptors(RAR). RAR bind to all-trans-retinoic acid(ATRA) to induce the transcription of genes responsible for cellular differentiation. Although most research concerning the chemotherapeutic efficacy of retinoids focuses on the ability of ATRA to decrease cancer cell proliferation, increase differentiation, or promote apoptosis; as CRC progresses, RAR expression is often lost, rendering treatment of CRCs with ATRA ineffective. Our laboratory focuses on the ability of dietary vitamin A to decrease CRC cell proliferation and invasion via RAR-independent pathways. This review discusses our research and others concerning the ability of retinoids to ameliorate the defective signaling pathways listed above and decrease tumor cell proliferation and invasion through both RAR-dependent and RAR-independent mechanisms.

  15. Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells

    Indian Academy of Sciences (India)

    Ji-Wang Zhang; Jian Gu; Zhen-Yi Wang; Sai-Juan Chen; Zhu Chen

    2000-09-01

    Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor (RAR) (including: PML-RAR, PLZF-RAR, NPM-RAR, NuMA-RAR or STAT5b-RAR) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.

  16. Influence of suppressor gene p16 on retinoic acid inducing cancer cell A549 differentiation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the role of suppressor gene p16 in the process of differential regulation of retinoic acid (RA) on the A549 lung cancer cells.Methods Tumor suppressor gene p16 was transferred into A549 cells and the cells were treated with all-trans retinoic acid (ATR) at the dosage of 5×10-6 mol/L for 4 d. After that, the proliferation and differentiation of A549 cells were examined by growth curve and cytometry analysis, the change of lung lineage-specific marker MUC1 was tested by immunohistochemical staining. Meanwhile, Western blot was used to observe the change of p16 protein expression in A549 cells treated with ATRA.Results ATRA could obviously inhibit the growth and induce the differentiation of A549 Cells that were transferred with p16 gene. There were more cells arrested in G1/G0 phase and the expression of MUG1 was markedly down-regulated than in control cells. The expression of p16 protein was up-regulated in A549 cells treated with ATRA.Conclusion Suppressor gene p16 could enhance the effects of RA and proliferated suppression and differential induction of A549 cells.

  17. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    Directory of Open Access Journals (Sweden)

    Yoshihiro Akimoto

    2014-06-01

    Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

  18. Relationship between struc-ture and function of JWA in the modulation of cell differ-entiation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To elucidate the structure characteristic, regulation of expression and the potential function of JWA——a novel retinoic acid responsible and cytoskeleton associate gene, a rat JWA homologue gene and a 621-bp JWA promoter fragment were cloned and analyzed. Using reverse transcription-polymerase chain reaction (RT-PCR), JWA mRNA expression in NIH3T3, K562 and human primary acute promyelocytic leukaemia (APL) cells have been investigated after treatment with all trans retinoic acid (ATRA), N-4-hydroxyphenyl-retinamide (4HPR), arsenic trioxide (As2O3), Phorbol-12-myristate-13-acetate (TPA) and dimethyl sulfoxide (DMSO). The results showed that there is a complete TPA responsive element (TRE) existed in the promoter of JWA at ?437 to ?443 bp; rat JWA homologue gene showed that there are four nucleotides different from human JWA within coding region. After treatment with TPA, an uneven pattern of JWA transcription existed in different cell lines, suggesting that even TPA induces cell differentiation in different cell lines, and it may be referred to different signal pathways. In ATRA pretreated APL cells, all the above chemicals induce cellular differentiation and down regulate JWA transcription in vitro. This suggests that pretreatment of ATRA on APL cells seems a precondition for turning on JWA involved signal pathway.

  19. Treatment with 5-Azacytidine Accelerates Acute Promyelocytic Leukemia Leukemogenesis in a Transgenic Mouse Model

    Science.gov (United States)

    Scaglioni, Pier Paolo; Cai, Lu Fan; Majid, Samia M.; Yung, Thomas M.; Socci, Nicholas D.; Kogan, Scott C.; Kopelovich, Levy; Pandolfi, Pier Paolo

    2011-01-01

    A key oncogenic force in acute promyelocytic leukemia (APL) is the ability of the promyelocytic leukemia–retinoic acid receptor α (PML-RARA) oncoprotein to recruit transcriptional repressors and DNA methyltransferases at retinoic acid–responsive elements. Pharmacological doses of retinoic acid relieve transcriptional repression inducing terminal differentiation/apoptosis of the leukemic blasts. APL blasts often harbor additional recurrent chromosomal abnormalities, and significantly, APL prevalence is increased in Latino populations. These observations suggest that multiple genetic and environmental/dietary factors are likely implicated in APL. We tested whether dietary or targeted chemopreventive strategies relieving PML-RARA transcriptional repression would be effective in a transgenic mouse model. Surprisingly, we found that 1) treatment with a demethylating agent, 5-azacytidine, results in a striking acceleration of APL; 2) a high fat, low folate/choline–containing diet resulted in a substantial but nonsignificant APL acceleration; and 3) all-trans retinoic acid (ATRA) is ineffective in preventing leukemia and results in ATRA-resistant APL. Our findings have important clinical implications because ATRA is a drug of choice for APL treatment and indicate that global demethylation, whether through dietary manipulations or through the use of a pharmacologic agent such as 5-azacytidine, may have unintended and detrimental consequences in chemopreventive regimens. PMID:21779489

  20. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Yonal Ipek

    2012-01-01

    Full Text Available Acute promyelocytic leukemia (APL is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa locus on chromosome 17, the great majority of which is t(15; 17(q24.1; q21.1 (Collins (1998, Melnick and Licht (1999, and Grimwade (1999. Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA is a subgroup of the retinoid family, which induces complete remission (CR in APL by causing differentiation and apoptosis in immature malignant promyelocytes rather than inducing cell death by cytotoxicity (Warrell et al. (1993, Liu et al. (2000, and Cassinat et al. (2001. ATRA-associated toxicity consisting of headache, fever, weakness, fatigue, dry skin, dermatitis, gastrointestinal disorders, and hypertriglyceridemia has been shown to be mild (Kurzrock et al. (1993. Herein, we describe a patient with APL that developed an erythematous reaction of the whole body followed by desquamation and exfoliation during ATRA therapy.

  1. Synchrotron small angle x-ray scattering study of dye-sensitized/-unsensitized TiO2 nanoparticle colloidal solution

    Institute of Scientific and Technical Information of China (English)

    Hong Xin-Guo; Du Lu-Chao; Ye Man-Ping; Weng Yu-Xiang

    2004-01-01

    The wide-gap semiconductor TiO2 nanoparticles with and without dye sensitization have been studied by small angle x-ray scattering using synchrotron radiation. Surface properties of the colloidal TiO2 nanoparticles have been analysed in terms of the surface fractal dimensions (Ds), showing that Ds changes from 3.25 to 2.34 when TiO2nanoparticles are sensitized by ATRA (all-trans-retinoic acid), which reveals that the surface of the particles become relatively smooth after dye sensitization. The size distribution of gyration radius of TiO2 nanoparticles in the colloids M(Rg) has been successfully determined by the Shull-Roess method. The main peak of M(Rg) for the unsensitized TiO2colloid is located at 2.1nm, corresponding to a spherical diameter of 5.4nm, and this value for the ATRA sensitized TiO2increases to 2.4nm, indicating a spherical diameter of 6.4nm. Such a size enlargement of TiO2 nanoparticles suggests that there is a coating of ATRA on the TiO2 surface, supporting the view that a monolayer of the dye has been attached to the surface of the TiO2 nanoparticle.

  2. THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE.

    Directory of Open Access Journals (Sweden)

    Pau Montesinos

    2011-12-01

    Full Text Available Differentiation syndrome (DS, formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO] in patients with acute promyelocytic leukemia (APL. The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Español de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005, in which more than one thousand patients were treated with ATRA plus idarubicin for induction.

  3. THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE.

    Directory of Open Access Journals (Sweden)

    Pau Montesinos

    2011-01-01

    Full Text Available

    Differentiation syndrome (DS, formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO] in patients with acute promyelocytic leukemia (APL. The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Español de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005, in which more than one thousand patients were treated with ATRA plus idarubicin for induction.

  4. STUDY ON EFFECTS OF QUERCETIN ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    钟璐; 陈芳源; 韩洁英; 邵念贤; 欧阳仁荣

    2003-01-01

    Objective To investigate the effect of quercetin on PML gene and protein expression and localization in leukemia cell lines. MethodsCell morphology was assayed by Wright,s stain and fluorescence stain, and PML Mrna expression by RT-PCR, PML protein localization by immuno fluorescence.ResultsNB4 and HL-60 cells differentiated morphologically after treatment with all trans retinoic acid (ATRA) while K562 cells did not differentiate. Typical apoptosis was found in each cell line after treatment with quercetin. Immuno fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with quercetin, the fusion protein disappeared in NB4 cells, PML protein relocated, then degraded. In HL-60 cells and K562 cells, PML protein also located and then degraded. The expression of PML Mrna was not changed in all three cell lines after treatment with ATRA or quercetin. ConclusionPML plays the role of differentiation and apoptosis inducer in leukemia cells at the translational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.

  5. NIR and visible investigation of some potential SERS-active substrates for studying antitumour agent all- trans retinoic acid

    Science.gov (United States)

    Beljebbar, A.; Sockalingum, G. D.; Morjani, H.; Angiboust, J. F.; Manfait, M.

    1997-01-01

    Red and near-infrared excited Fourier transform surface-enhanced Raman spectra of an anticancer agent, all- trans retinoic acid (ATRA), adsorbed on gold island films are reported. Best results have been obtained with plates 80 Å and 40 Å thick respectively in the red and near-infrared and at concentrations of 10 -5 and 5 × 10 -6 M with a spinning system. The use of near-infrared laser excitation with low photon energy, allows us to overcome the problems of isomerisation when the sample is exposed for a long time to the laser radiation. Comparison between the Raman and SERS spectra in the visible shows that the adsorption on the surface does not perturb the structure of ATRA and confirms the long range enhancement of the island films with this type of molecule. Spectral data show that while gold island films and colloids are appropriate substrates for use with red excitation, silver and gold colloids as well as gold island films exhibit satisfactory enhancement levels in the near-infrared. This study will in the future allow us to choose the appropriate system that will serve to investigate the interaction of ATRA with its target in vitro and the effect of this differentiating agent in human leukaemia cell lines such as K562 and HL60.

  6. All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.

    Science.gov (United States)

    Chien, Chiao-Yun; Yuan, Tze-An; Cho, Candy Hsin-Hua; Chang, Fang-Pei; Mao, Wan-Yu; Wu, Ruei-Ren; Lee, Hsuan-Shu; Shen, Chia-Ning

    2016-09-01

    Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control. PMID:27381866

  7. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    Science.gov (United States)

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  8. Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ai-Guo, E-mail: wangaiguotl@hotmail.com; Song, Ya-Nan; Chen, Jun; Li, Hui-Ling; Dong, Jian-Yi; Cui, Hai-Peng; Yao, Liang; Li, Xue-Feng; Gao, Wen-Ting; Qiu, Ze-Wen; Wang, Fu-Jin; Wang, Jing-Yu, E-mail: wangjingyus@163.com

    2014-09-26

    Highlights: • The activation of RAS/ERK is insufficient to inhibit RXRα function and deplete RA. • The retinoid metabolism-related genes are down-regulated by ras oncogene. • The atRA has no effect on preventing hepatic tumorigenesis or curing the developed hepatic nodules. - Abstract: Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week

  9. Pulmonary administration of integrin-nanoparticles regenerates collapsed alveoli.

    Science.gov (United States)

    Horiguchi, Michiko; Kojima, Hisako; Sakai, Hitomi; Kubo, Hiroshi; Yamashita, Chikamasa

    2014-08-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causes widespread and irreversible alveoli collapse. In search of a treatment target molecule, which is able to regenerate collapsed alveoli, we sought to identify a factor that induces differentiation in human alveolar epithelial stem cells using all-trans retinoic acid (ATRA), whose alveolar repair capacity has been reported in animal experiments. When human alveolar epithelial stem cells were exposed to ATRA at a concentration of 10μM for over seven days, approximately 20% of the cells differentiated into each of the type-I and type-II alveolar epithelial cells that constitute the alveoli. In a microarray analysis, integrin-α1 and integrin-β3 showed the largest variation in the ATRA-treated group compared with the controls. Furthermore, the effect of the induction of differentiation in human alveolar epithelial stem cells using ATRA was suppressed by approximately one-fourth by siRNA treatments with integrin α1 and integrin β3. These results suggested that integrin α1 and β3 are factors responsible for the induction of differentiation in human alveolar epithelial stem cells. We accordingly investigated whether integrin nanoparticles also had a regenerative effect in vivo. Elastase-induced COPD model mouse was produced, and the alveolar repair effect of pulmonary administration using nanoparticles of integrin protein was evaluated by X-ray CT scanning. Improvement in the CT value in comparison with an untreated group indicated that there was an alveolar repair effect. In this study, it was shown that the differentiation-inducing effect on human alveolar epithelial stem cells by ATRA was induced by increased expression of integrin, and that the induced integrin enhanced phosphorylation signaling of AKT, resulting in inducing differentiations. Furthermore, the study demonstrated that lung administration of nanoparticles with increased solubility and stability of integrin

  10. Hermit crab (Decapoda, Anomura attraction to dead gastropod baits in an infralittoral algae bank

    Directory of Open Access Journals (Sweden)

    Juarez C. B. Pezzuti

    2002-06-01

    Full Text Available Hermit crabs use gastropod shells as shelter and are adapted to follow chemical cues released from tissues of dead or injured gastropods as a way to find new and more adequate shells. The species composition, crab size, shell types adequacy and physical condition were compared between attracted individuals and crabs collected in previous samples. The previous sampling was carried out in five areas before each experiment. Then, five baits of crushed gastropods in nylon net bags were installed in these areas. Three samples were taken at 30min intervals, capturing all crabs within a circle of 60cm diameter. Attraction of hermit crabs was tested for four different gastropod baits to verify specificity of the chemical cues. Clibanarius antillensis, Pagurus brevidactylus and Paguristes tortugae were collected in the study area. Pagurus brevidactylus, the smallest species, turned out to be more attracted than the 2 other species. The results showed that attracted crabs utilized more gastropod shell types than that collected in previous samples, however shell utilization pattern did not differ between them. Attracted animals were slightly smaller (shield length than those collected in the previous samples but did not present significant differences in shell adequacy and condition. The four experimental baits attracted the crabs in similar ways not indicating a specific response from the crabs. The fact that attracted animals were smaller suggested that the attraction to dead gastropods might enable the acquisition of a new and larger shell and, consequently, chains of shell exchange between the attracted crabs.Ermitões utilizam conchas de gastrópodes para abrigo. Conchas novas e mais adequadas podem ser encontradas pelos ermitões pois estes são atraídos por substâncias químicas liberadas pelos tecidos de gastrópodes feridos ou mortos. A adequação, condição e tipo das conchas e a composição de espécies e o tamanho dos ermitões foram

  11. Identification of tumor invasion-related differentially expressed genes in different grades and all-trans retinoic acid-treated astrocytoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Yangyun Han; Chao You

    2008-01-01

    BACKGROUND: Although several genetic aberrations and gene expressional changes have been shown to exist in tumors and different grades of astrocytomas, as well as in normal tissues, the gene profiling and genetic pathways associated with malignant transformation and progression remain unclear. OBJECTIVE: To identity differentially expressed genes related to tumor invasion from various grades and all-trans retinoic acid (ATRA)-treated astrocytoma cell lines by cDNA microarray. DESIGN, TIME AND SETTING: In vitro gene experiment was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA from January to October 2007. MATERIALS: Two different grades of astrocytoma cell lines CHG-5 (WHO grade Ⅱ) and SHG-44 (WHOgrade Ⅳ) were developed by our laboratory; a cell differentiation-inducing agent ATRA and a human cDNA microarray technology were used to determine differentially expressed genes (City University of Hong Kong). METHODS: Total RNA was extracted using the Trizol test kit. Reverse transcription was performed using Superscript Ⅱ reverse transcriptase. The eDNA product (target DNA) was marked with fluorochromes Cy3 (normal SHG-44) and Cy5 (CHG-5 or ATRA-treated SHG-44), followed by chip hybridization. MAIN OUTCOME MEASURES: Gene expression profiles of CHG-5 vs. SttG-44 and ATRA-treated vs. Normal SHG-44 were performed to identify differentially expressed genes. Several of these genes were randomly selected for Northern Blot analysis. The identification of genes that were similarly regulated (overlapping) was performed by comparing gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS: No significant differences were observed between CHG5 and SHG-44 cell line morphology. Under confocal microscopy. GFAP staining intensity of CHG5 cells was greater than SHG-44 cells (t = 6.078, P = 0.004). Growth curve analysis demonstrated that the speed of SHG-44 cell

  12. The Influence of All-trans Retinoic Acid on Cardiac Function of Rats with Diabetic Cardiomyopathy%全反式维甲酸对糖尿病心肌病大鼠心功能的影响

    Institute of Scientific and Technical Information of China (English)

    黄俊华; 陈继洲; 陈红梅; 万雨明; 李霞; 尤媛媛

    2011-01-01

    Objective To investigate the influence of all-trans retinoic acid(ATRA) on cardiac function of rats with diabetic cardiomyopathy. Mothocls The diabetic model were established in 20 rats by intraperitoneal injection of streptozotocin ( 20 mg/kg). Then the rats were randomly divided into ATRA group and DCM group after 4 weeks. The rats in ATRA group were given ATRA with 20 mg/( kg · d) by intragastric administration,while equal volume purified water were given in DCM group. The left ventricular mass index(LVMI) ,left ventricular systolic pressure(LVSP) ,left ventricular end-diastolic pressure(LVEDP) ,the maximal rates of increase/decline of left ventricular pressure( ± dp/dtmax),the maximal rates of decrease of left ventricular pressure (-dp/dtmax) and the time of the maximal rates of decrease of left ventricular pressure (-dp/dtmax) were exminated at 8 weeks later. The myocardial ultrastrncture were observed with electron micrescope. Results All-trans retinoic acid could decreasethe values of LVMI,LVEDP and ( t-dp/dt ), while increase the LVSP, ( + dp/dtmax) and ( - dp/dtmax) of rats with diabetic. The electron micrescopy results showed collagen aceertion,bioblast dilatation in myocardial matrix were decreased,the break and solution of myofibril were slight,the myocardium was well-arranged,the dilatation of endotheliocyte in capillary were slight than in DCM group. Conclusion All-trans retinoic acid could improve the systolic and diastolic function of myocatdium,relieve myocardial hypertrophy in rats with diabetic cardiomyopathy.%目的:探讨全反式维甲酸(ATRA)对糖尿病心肌病(DCM)大鼠心功能的影响.方法:20只Wistar大鼠腹腔注射链脲佐菌素制作糖尿病模型,4周后随机取10只予ATRA 20mg/(Kg·d)灌胃(维甲酸组),另10只予等量纯净水(糖尿病组).8周后分别测量各组左室重量指数(LVMI),左室收缩压(LVSP)、左室舒张末期压(LV-EDP)、室内压最大上升速率(+dp/dtmax)、室

  13. Keratins 2 and 4/13 in reconstituted human skin are reciprocally regulated by retinoids binding to nuclear receptor RARalpha.

    Science.gov (United States)

    Virtanen, Marie; Sirsjö, Allan; Vahlquist, Anders; Törmä, Hans

    2010-07-01

    Disorders of keratinization are often treated with vitamin A derivatives (retinoids) which affect keratinocyte differentiation, including keratin (KRT) gene expression. In vivo, suprabasal keratinocytes normally express only keratin (K) 1, K2 and K10, but after topical application of all-trans retinoic acid (ATRA), the granular cells will additionally express K4 and K13, i.e. keratins normally present in oral mucosa and in cultured epidermal keratinocytes. To learn more about the retinoid regulation of keratin expression under in vivo-like conditions, we cultured keratinocytes on de-epidermized dermis in only 0.5% serum. These cells produce a normal-looking epidermis that expresses high mRNA levels of KRT1, KRT2 and KRT10, but minimal amounts of KRT4 and KRT13. Addition of ATRA to the medium for 48 h caused a dose-dependent increase in KRT4/KRT13 and a down-regulation of KRT2 mRNA. An increase in K4 protein was also found. The response was greater than the up-regulation of another retinoid-regulated gene, CRABPII. By studying 10 retinoids with different affinities for the retinoic acid receptors (RAR) and retinoid X receptors (RXR) isoforms, the reciprocal expression of KRT2 and KRT4/KRT13 could be connected with agonists for RARalpha. Two of these agonists, CD336/Am580 and CD2081, altered the expression profile with similar potency as the pan-RAR agonists ATRA and CD367. Co-addition of a pan-RAR antagonist (CD3106/AGN193109) markedly inhibited the induction of KRT4/KRT13 expression, whereas the down-regulation of KRT2 was less affected. In conclusion, RARalpha agonists elicit a reciprocal modulation of KRT2 and KRT4/KRT13 expression in human epidermis, but whether or not the keratin genes also possess RARalpha-specific regulatory elements is still unclear.

  14. Critical role of the H6-H7 loop in the conformational adaptation of all-trans retinoic acid and synthetic retinoids within the ligand-binding site of RARalpha.

    Science.gov (United States)

    Mailfait, S; Thoreau, E; Belaiche, D; Formstecher And B Sablonniè, P

    2000-06-01

    The pleiotropic effects of the natural and synthetic retinoids are mediated by the activation of the two subfamilies of nuclear receptors, the retinoic acid receptors (RARs) and the retinoic X receptors (RXRs). At the molecular level, these events begin with the specific ligand recognition by a nuclear receptor subtype. The adaptation of ligands to the receptor binding site leads to an optimal number of interactions for binding and selectivity which justifies elucidation of the structural requirements of the ligand binding pocket. To explore the contribution of H6-H7 loop folding in the ligand-induced conformational changes explained by the mouse-trap model, four RARalpha mutants were constructed. Ligand binding and transactivation studies revealed that three residues from the H6-H7 loop (Gly(301), Phe(302) and Gly(303)) are critical for the conformational adaptation of both synthetic agonists and antagonists. Model building and analysis of both RARalpha-ATRA and RARalpha-CD367 complexes demonstrate that accommodation of CD367 results in a less tight contact of the saturated ring of this ligand with the amino acid side chains of the receptor ligand-binding pocket compared with that of ATRA. According to the flexibility of the agonists tested (ATRA>TTNPB=Am580> CD367), we observed a decrease in binding that was dependent on ligand structure rigidity. In contrast, the binding and transactivating activities of the L266A mutant confirmed the structural constraints imposed by synthetic ligands on binding affinity for the receptor and revealed that subtle local rearrangements induced by specific conformational adaptation changes result in different binding affinities. Our results illustrate the dynamic nature of the interaction between RARalpha and its ligands and demonstrate the critical role of the H6-H7 loop in the binding of both synthetic retinoid agonists and antagonists.

  15. Neuregulins are essential for spermatogonial proliferation and meiotic initiation in neonatal mouse testis.

    Science.gov (United States)

    Zhang, JiDong; Eto, Ko; Honmyou, Asuka; Nakao, Kazuki; Kiyonari, Hiroshi; Abé, Shin-ichi

    2011-08-01

    The transition from mitosis to meiosis is unique to germ cells. In murine embryonic ovaries and juvenile testes, retinoic acid (RA) induces meiosis via the stimulated by retinoic acid gene 8 (Stra8), but its molecular pathway requires elucidation. We present genetic evidence in vivo and in vitro that neuregulins (NRGs) are essential for the proliferation of spermatogonia and the initiation of meiosis. Tamoxifen (TAM) was injected into 14-day post-partum (dpp) Sertoli cell-specific conditional Nrg1(Ser-/-) mutant mice. TAM induced testis degeneration, suppressed BrdU incorporation into spermatogonia and pre-leptotene primary spermatocytes, and decreased and increased the number of STRA8-positive and TUNEL-positive cells, respectively. In testicular organ cultures from 5-6 dpp wild-type mice and cultures of their re-aggregated spermatogonia and Sertoli cells, FSH, RA [all-trans-retinoic acid (ATRA), AM580, 9-cis-RA] and NRG1 promoted spermatogonial proliferation and meiotic initiation. However, TAM treatment of testicular organ cultures from the Nrg1(Ser-/-) mutants suppressed spermatogonial proliferation and meiotic initiation that was promoted by FSH or AM580. In re-aggregated cultures of purified spermatogonia, NRG1, NRG3, ATRA and 9-cis-RA promoted their proliferation and meiotic initiation, but neither AM580 nor FSH did. In addition, FSH, RAs and NRG1 promoted Nrg1 and Nrg3 mRNA expression in Sertoli cells. These results indicate that in juvenile testes RA and FSH induced meiosis indirectly through Sertoli cells when NRG1 and NRG3 were upregulated, as NRG1 amplified itself and NRG3. The amplified NRG1 and NRG3 directly induced meiosis in spermatogonia. In addition, ATRA and 9-cis-RA activated spermatogonia directly and promoted their proliferation and eventually meiotic initiation.

  16. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.

  17. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Anna Falanga

    2011-12-01

    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  18. Protective effect of all-trans retinoic acid on injury of human immortalized hepatocytes induced by sodium arsenite%全反式维甲酸对亚砷酸钠致人肝细胞损伤保护性作用的研究

    Institute of Scientific and Technical Information of China (English)

    孙惠昕; 胡新欣; 张微; 高彦辉; 孙殿军

    2012-01-01

    目的 观察全反式维甲酸(ATRA)对亚砷酸钠致人肝细胞系(HHL)-5细胞损伤的保护性作用,探讨可能机制.方法 采用细胞培养方法,体外培养HHL-5细胞48 h后进行实验,实验分为4组:正常组、ATRA组、亚砷酸钠组、ATRA+亚砷酸钠组.用细胞增殖实验(WST)观察HHL-5细胞的活力;生物化学方法测定各组HHL-5细胞内超氧化物歧化酶(SOD)、谷胱甘肤过氧化物酶(GSH-Px)的活力及丙二醛(MDA)的含量和细胞培养液中谷草转氨酶(AST)的活力;透射电镜观察各组细胞超微结构的变化.结果 亚砷酸钠组HHL-5细胞活力(0.57±0.02)与正常组(0.70±0.01)比较,差异有统计学意义(P< 0.05);SOD、GSH-Px、MDA、AST [(153.84±2.35 )U/mg Prot、(0.08±0.02)U/mg Prot、(4.15±0.50)nmol/mg Prot、(265.43±4.62)×103 U/L]与正常组[(237.41±18.30) U/mg Prot、(0.93±0.02)U/mg Prot、(2.26±0.40)nmol/mg Prot、(177±9.85)×103 U/L]比较,差异有统计学意义(P均.<0.05).ATRA+亚砷酸钠组HHL-5细胞活力(0.65±0.04)与亚砷酸钠组比较,差异有统计学意义(P<0.05);SOD、GSH-Px、MDA、AST[(286.85±3.39)U/mg Prot、(0.56±0.09)U/mg Prot、(3.36±0.37)nmol/mg Prot、(220.02±1.07)×103 U/L]与亚砷酸钠组比较,差异有统计学意义(P均< 0.05).电镜结果显示,亚砷酸钠组同正常组及ATRA组比较,细胞表面微绒毛减少,双层核膜结构不清,胞质内可见空泡样变,肝糖原凝集;ATRA+亚砷酸钠组上述损伤程度减轻.结论 ATRA通过提高HHL-5细胞内抗氧化酶的活力,清除或者减少氧自由基对细胞的损伤,从而发挥保护作用.%Objective To investigate the protective effect of all-trans retinoic acid (ATRA) on injury of human immortalized hepatocytes (HHL-5 cells ) induced by sodium arsenite and possible mechanisms.Methods After cultured for 48 h,HHL-5 cells were divided into four groups:normal group,ATRA group,sodium arsenite group and ATRA + sodium arsenite group.HHL-5 cell viability

  19. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Tamer M Fouad

    2011-01-01

    Full Text Available

    The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate

  20. Nuclear and mitochondrial multilocus phylogeny and survey of alkaloid content in true salamanders of the genus Salamandra (Salamandridae).

    Science.gov (United States)

    Vences, Miguel; Sanchez, Eugenia; Hauswaldt, J Susanne; Eikelmann, Daniel; Rodríguez, Ariel; Carranza, Salvador; Donaire, David; Gehara, Marcelo; Helfer, Véronique; Lötters, Stefan; Werner, Philine; Schulz, Stefan; Steinfartz, Sebastian

    2014-04-01

    The genus Salamandra represents a clade of six species of Palearctic salamanders of either contrasted black-yellow, or uniformly black coloration, known to contain steroidal alkaloid toxins in high concentrations in their skin secretions. This study reconstructs the phylogeny of the genus Salamandra based on DNA sequences of segments of 10 mitochondrial and 13 nuclear genes from 31 individual samples representing all Salamandra species and most of the commonly recognized subspecies. The concatenated analysis of the complete dataset produced a fully resolved tree with most nodes strongly supported, suggesting that a clade composed of the Alpine salamander (S. atra) and the Corsican fire salamander (S. corsica) is the sister taxon to a clade containing the remaining species, among which S. algira and S. salamandra are sister species. Separate analyses of mitochondrial and nuclear data partitions disagreed regarding basal nodes and in the position of the root but concordantly recovered the S. atra/S. corsica as well as the S. salamandra/S. algira relationship. A species-tree analysis suggested almost simultaneous temporal splits between these pairs of species, which we hypothesize was caused by vicariance events after the Messinian salinity crisis (from late Miocene to early Pliocene). A survey of toxins with combined gas chromatography/mass spectroscopy confirmed the presence of samandarine and/or samandarone steroidal alkaloids in all species of Salamandra as well as in representatives of their sister group, Lyciasalamandra. Samandarone was also detected in lower concentrations in other salamandrids including Calotriton, Euproctus, Lissotriton, and Triturus, suggesting that the presence and possible biosynthesis of this alkaloid is plesiomorphic within the Salamandridae. PMID:24412216

  1. Role of JWA in acute promyelocytic leukemia cell differentiation and apoptosis triggered by retinoic acid, 12-tetradecanoylphorbol-13-acetate and arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    JWA, a cytoskeleton associated gene, was primarily found to be regulated by all trans-retinoic acid (ATRA), 13 cis-retinoic acid (13 cis-RA) and 12-tetradecano- ylphorbol-13-acetate (TPA). Our previous data showed that JWA might be involved in both cellular differentiation and apoptosis induced by several chemicals. In this study, we addressed the possible mechanism of JWA in the regulation of cell differentiation and apoptosis in NB4, a human acute promyelocytic leukemia cell line. CD11b/CD33 expression and cell cycle were analyzed for detecting of cell differentiation and apoptosis. Both reverse-transcription polymerase chain reaction (RT-PCR) and Western blot assays were used for understanding the expressions of JWA. The results showed that under the indicated concentrations ATRA (10?6 mol/L) and As2O3 (10?6 mol/L) induced cell differentiation and apoptosis separately; while both 4HPR (10?6 mol/L) and TPA (10?7 mol/L) showed dual-directional effects on NB4 cells, they not only trigger cells' differentiation but also induce cells apoptosis at the same time. All chemicals up-regulated JWA expression whatever they trigger cells either differentiation or apoptosis; however, it seems that the chemicals have no effect on PML/RAR? in the treated NB4 cells. Anti-sense JWA oligonucleotide could partially block the ability of TPA in inducing cell differentiation and apoptosis via direct signal pathway. Interestingly, a high molecular weight JWA protein (JWAF) was identified only in de novo primary APL cells and it was also responsible for ATRA treatment. It raises questions of whether the JWAF is a novel APL specific marker and, how it was involved in the known mechanism of APL.

  2. Acute promyelocytic leukemia, study of predictive factors for Differentiation Syndrome, single center experience

    International Nuclear Information System (INIS)

    Reports about patients with acute promyelocytic leukemia from the Middle East are few; in this study we are reporting our single center experience of treating 29 patients over 6 years. Acute promyelocytic leukemia treatment response is markedly improved after the introduction of ATRA. Treatment related complication is still an important issue particularly Differentiation Syndrome. Prediction to its occurrence has been tried by other groups. We aimed to study all the possible predictive factors of acute promyelocytic leukemia. Our chemotherapy induction protocol is AIDA protocol which includes ATRA 45 mg/m2/d in divided doses every 12h, and Idarubicin 12 mg/ m2/d IV on days 3, 5, 7, and 9. Differentiation Syndrome occurred in 48.3% of patients and was mainly presented by pulmonary symptoms in 55.2%, 6 cases died during induction. None of the predictive factors studied showed a statistically significant difference between patients who developed Differentiation Syndrome and those who did not. Differentiation Syndrome did not affect overall survival. Cox regression showed an inverse yet a non significant association between PET- HEMA and overall survival probability (P = 0.168). In conclusion, Differentiation Syndrome has no clear predictive factor to date. The best approach is to hold ATRA and give dexamethasone which is quite effective as reported in the literature. PETHEMA risk model has a moderately significant prognostic value look for all possible predictive factors of Differentiation syndrome (DS) which were first described in 1992 by frankel et al. (4) and represented the major complication through this disease course: studies had reported conflicting results about this (5,6). In addition we will compare our data to other areas of the world

  3. Screening of differentially expressed genes related to differentiation and proliferation by gene expression profiling of different grade astrocytoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Yangyun Han; Chao You

    2008-01-01

    BACKGROUND: The detection of differential gene expression in brain is possible by cDNA microarray technology, and the screening of differentially expressed genes might provide a biological basis for gene-targeted therapy for tumors. OBJECTIVE: To detect the differential expression of genes among astrocytoma SHG-44 (WHO grade IV), CHG-5 (WHO grade II), and ATRA-treated SHG-44 cell lines by cDNA microarray. DESIGN: Laboratory experiments in vitro.SETTING: Department of Neurobiology, the Third Military Medical University. MATERIALS: The experiment was performed at the Department of Neurobiology in the Third Military Medical University of the Chinese PLA from January to October 2007. The SHG-44 cell line (WHO grade Ⅳ) was established by Prof. Ziwei Du, and the CHG-5 cell line (WHO grade II) was set up by Prof. Xiuwu Bian from the Third Military Medical University of the Chinese PLA. The cDNA microarray containing 9182 known genes was prepared and provided by Dr. Yang Zhong at the City University of Hong Kong. MAIN OUTCOME MEASURES: The identification of genes that were similarly regulated (overlapping) during tumor progression and differentiation, by comparison of gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS: Thirty-one overlapping genes were found to have similar regulatory effects on astrocytomas; among them, twenty genes were up-regulated and eleven were down-regulated in both comparisons between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. The four reported genes, SERPINF1, MAPK11, HIF1A and SOD2, were up-regulated in this study.CONCLUSION: The differentially expressed genes in different grade astrocytoma cell lines were revealed primarily by cDNA microarray; among them, five identified overlapping genes, SERPINF1, MAPK11, DCTN2, HIF1A and SOD2, were related to the malignant progression of astrocytoma cells.

  4. Transcriptional upregulation of restin by p53

    Institute of Scientific and Technical Information of China (English)

    WANG RuiHua; LU Fan; FU HaiYan; WU YouSheng; YANG GuoDong; ZHAO WenMing; Zhao ZhongLiang

    2007-01-01

    Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid ( ATRA ) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RP△p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.

  5. Inhibition of ALDH1A1 activity decreases expression of drug transporters and reduces chemotherapy resistance in ovarian cancer cell lines.

    Science.gov (United States)

    Januchowski, Radosław; Wojtowicz, Karolina; Sterzyńska, Karolina; Sosińska, Patrycja; Andrzejewska, Małgorzata; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

    2016-09-01

    The high mortality of ovarian cancer patients results from the failure of treatment caused by the inherent or acquired chemotherapy drug resistance. It was reported that overexpression of aldehyde dehydrogenase A1 (ALDH1A1) in cancer cells can be responsible for the development of drug resistance. To add the high expression of the drug transporter proteins the ALDHA1 is considered as a molecular target in cancer therapy. Therefore, we analysed drug-resistant ovarian cancer cell lines according to ALDHA1 expression and the association with drug resistance. The expression of ALDH1A1, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) was determined using a microarray and confirmed by Q-PCR, western blot and fluorescence analysis. ALDH1A1 activity was determined using an Aldefluor assay. The impact of all-trans retinoic acid (ATRA) and diethylaminobenzaldehyde (DEAB) on chemotherapy resistance was assessed by the MTT chemosensitivity assay. The most abundant expression of ALDH1A1 was noted in paclitaxel- and topotecan-resistant cell lines where two populations of ALDH-positive and ALDH-negative cells could be observed. Those cell lines also revealed the overexpression of P-gp and BCRP respectively, and were able to form spheres in non-adherent conditions. Pre-treatment with ATRA and DEAB reduced chemotherapy resistance in both cell lines. ATRA treatment led to downregulation of the ALDH1A1, P-gp and BCRP proteins. DEAB treatment led to downregulation of the P-gp protein and BCRP transcript and protein. Our results indicate that ALDH1A1-positive cancer cells can be responsible for drug resistance development in ovarian cancer. Developing more specific ALDH1A1 inhibitors can increase chemotherapy effectiveness in ovarian cancer.

  6. Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

    Directory of Open Access Journals (Sweden)

    Ryan J Blower

    Full Text Available Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense peptides. In this study, a number of cationic antimicrobial peptides (CAMPs were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2 and a short beta-defensin-derived peptide (Peptide 4 of hBD-3 were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

  7. Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

    Science.gov (United States)

    Blower, Ryan J; Barksdale, Stephanie M; van Hoek, Monique L

    2015-01-01

    Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense) peptides. In this study, a number of cationic antimicrobial peptides (CAMPs) were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis. PMID:26196513

  8. Virulence of mixed fungal infections in honey bee brood

    Directory of Open Access Journals (Sweden)

    Vojvodic Svjetlana

    2012-03-01

    Full Text Available Abstract Introduction Honey bees, Apis mellifera, have a diverse community of pathogens. Previous research has mostly focused on bacterial brood diseases of high virulence, but milder diseases caused by fungal pathogens have recently attracted more attention. This interest has been triggered by partial evidence that co-infection with multiple pathogens has the potential to accelerate honey bee mortality. In the present study we tested whether co-infection with closely related fungal brood-pathogen species that are either specialists or non-specialist results in higher host mortality than infections with a single specialist. We used a specially designed laboratory assay to expose honey bee larvae to controlled infections with spores of three Ascosphaera species: A. apis, the specialist pathogen that causes chalkbrood disease in honey bees, A. proliperda, a specialist pathogen that causes chalkbrood disease in solitary bees, and A. atra, a saprophytic fungus growing typically on pollen brood-provision masses of solitary bees. Results We show for the first time that single infection with a pollen fungus A. atra may induce some mortality and that co-infection with A. atra and A. apis resulted in higher mortality of honey bees compared to single infections with A. apis. However, similar single and mixed infections with A. proliperda did not increase brood mortality. Conclusion Our results show that co-infection with a closely related fungal species can either increase or have no effect on host mortality, depending on the identity of the second species. Together with other studies suggesting that multiple interacting pathogens may be contributing to worldwide honey bee health declines, our results highlight the importance of studying effects of multiple infections, even when all interacting species are not known to be specialist pathogens.

  9. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Ola Khorshid

    2011-12-01

    Full Text Available The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate, toxicity and OS.

  10. Moth sex pheromone receptors and deceitful parapheromones.

    Directory of Open Access Journals (Sweden)

    Pingxi Xu

    Full Text Available The insect's olfactory system is so selective that male moths, for example, can discriminate female-produced sex pheromones from compounds with minimal structural modifications. Yet, there is an exception for this "lock-and-key" tight selectivity. Formate analogs can be used as replacement for less chemically stable, long-chain aldehyde pheromones, because male moths respond physiologically and behaviorally to these parapheromones. However, it remained hitherto unknown how formate analogs interact with aldehyde-sensitive odorant receptors (ORs. Neuronal responses to semiochemicals were investigated with single sensillum recordings. Odorant receptors (ORs were cloned using degenerate primers, and tested with the Xenopus oocyte expression system. Quality, relative quantity, and purity of samples were evaluated by gas chromatography and gas chromatography-mass spectrometry. We identified olfactory receptor neurons (ORNs housed in trichoid sensilla on the antennae of male navel orangeworm that responded equally to the main constituent of the sex pheromone, (11Z,13Z-hexadecadienal (Z11Z13-16Ald, and its formate analog, (9Z,11Z-tetradecen-1-yl formate (Z9Z11-14OFor. We cloned an odorant receptor co-receptor (Orco and aldehyde-sensitive ORs from the navel orangeworm, one of which (AtraOR1 was expressed specifically in male antennae. AtraOR1•AtraOrco-expressing oocytes responded mainly to Z11Z13-16Ald, with moderate sensitivity to another component of the sex pheromone, (11Z,13Z-hexadecadien-1-ol. Surprisingly, this receptor was more sensitive to the related formate than to the natural sex pheromone. A pheromone receptor from Heliothis virescens, HR13 ( = HvirOR13 showed a similar profile, with stronger responses elicited by a formate analog than to the natural sex pheromone, (11Z-hexadecenal thus suggesting this might be a common feature of moth pheromone receptors.

  11. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells. PMID:26573109

  12. Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins: is there a perspective in lung cancer treatment?

    Directory of Open Access Journals (Sweden)

    Angela Alama

    Full Text Available Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated.We determined the activity of α-neurotoxins from Naja atra (short-chain neurotoxin, α-cobrotoxin and Naja kaouthia (long-chain neurotoxin, α-cobratoxin in vitro by cytotoxicity measurements in 5 lung cancer cell lines, by colony formation assay with α7nAChRs expressing and non-expressing cell lines and in vivo by assessing tumor growth in an orthotopic Non-Obese Diabetic/Severe Combined Immunodeficient (NOD/SCID mouse model system utilizing different treatment schedules and dosages.No statistically significant reduction in tumor growth was observed in the treatment arms in comparison to the control for both toxins. Paradoxically α-cobrotoxin from Naja atra showed the tendency to enhance tumor growth although, even in this case, the statistical significance was not reached.In conclusion our results show that, in contrast with other reports, the nAChR inhibitors α-cobratoxin from N. kaouthia and α-cobrotoxin from N. atra neither suppressed tumor growth nor prolonged the survival of the treated animals.

  13. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  14. Transcriptional upregulation of restin by p53

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid ( ATRA ) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RP?p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.

  15. Human trafficking and human (in)security : the role of the State of Myanmar as a security provider

    OpenAIRE

    Swe Zin Linn Phyu

    2012-01-01

    Dissertação de mestrado em Relações Internacionais O ser humano é confrontado com problemas de insegurança, tais como tráfico de seres humanos, migração ilegal, pobreza, degradação ambiental, pirataria e crimes transnacionais resultantes da globalização. A grande maioria das mulheres e jovens birmanesas são atraídas pelas redes de traficantes, que trabalham em grupos organizados ou individualmente. As vitimas são levadas para a Tailândia e vendidas como prostitutas. As causas e...

  16. Cambios en la actividad antioxidante en frutos de mortiño (vaccinium meridionale sw.) durante su desarrollo y maduración

    OpenAIRE

    Gaviria Montoya, Carlos; Hernández Arredondo, Juan David; Lobo Arias, Mario; Medina Cano, Clara Inés; Rojano, Benjamín Alberto

    2012-01-01

    Resumen. Los frutos de mortiño (Vaccinium meridionale Sw.) han atraído el interés de los consumidores debido a su alto contenido de compuestos polifenólicos y actividad antioxidante; sin embargo, no se ha realizado ninguna evaluación sobre los cambios durante su crecimiento y maduración. En este estudio se evaluó la variación en el contenido de fenoles y antocianinas totales y de la actividad antioxidante por las metodologías TEAC-ABTS, TEAC-DPPH, FRAP y ORAC. El fruto de mortiño presentó una...

  17. BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Cione, Erika [Department of Pharmacy, Health and Nutritional Sciences, Ed. Polifunzionale, University of Calabria, 87036 Rende, CS (Italy); Fletcher, Steven [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Kane, Maureen A., E-mail: mkane@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States)

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.

  18. Mejora de la competitividad del sistema portuario español mediante la optimización del servicio de manipulación de mercancías

    OpenAIRE

    Parra Serrano, María del Pilar

    2012-01-01

    El transporte marítimo, responsable de la canalización del 90% de los flujos comerciales internacionales, se organiza en torno a los puertos. Éstos, que resultan plataformas indispensables para el desarrollo de la economía, compiten entre sí para maximizar el tráfico atraído hacia sus instalaciones. El papel estratégico de los puertos tiene un expreso reconocimiento en el contexto de la Unión Europea, tanto desde la óptica del comercio como bajo el prisma del transporte. No en vano, por lo...

  19. Estudo ecotoxicológico da exposição ao chumbo e à nanopartícula de dióxido de titânio em Hoplias malabaricus

    OpenAIRE

    Rossi, Stéfani Cibele

    2013-01-01

    Resumo: O aumento do uso de nanomateriais em diversos produtos nas diferentes áreas, tais como eletrônicos, cosméticos, alimentos e medicamentos tem atraído a atenção da comunidade científica devido as propriedades desconhecidas desses materiais, tais como a cinética no ambiente e a interação com outras substâncias presentes no mesmo. Apesar de diferentes estudos terem demostrado baixa toxicidade das nanopartículas de dióxido de titânio (TiO2),outros apontam para um possível efeito modulador ...

  20. Caracterización de las antocianinas de la flor de ceibo como sensibilizadores naturales para su uso en celdas fotovoltaicas

    OpenAIRE

    María Paula Enciso; María Fernanda Cerdá Bresciano

    2014-01-01

    La energía solar es la fuente de energía más promisoria del futuro, ya que la conversión directa de luz solar en energía eléctrica mediante el uso de celdas solares posee muchas ventajas sobre los métodos usados en la actualidad, debido a que no genera desechos o contaminantes.En particular, las celdas solares sensibilizadas con pigmentos (DSSC) o celdas de Graetzel representan una alternativa a las convencionales celdas solares de silicio. En las últimas tres décadas han atraído considerable...

  1. INCENDIARIOS "Es preferible morir por el fuego, en combate, que morir en casa, por el hambre: Fidel Castro" Arson

    OpenAIRE

    Lisieux Elaine de BorbaTelles; Helena Dias de Castro Bins; Alcina Juliana Soares Barros; Franklin Escobar Córdoba

    2012-01-01

    Antecedentes. El concepto de fuego siempre ha atraído la atención del hombre. En la literatura abundan referencias a este término, que tanto puede representar poder y pasión como terror y destrucción. El incendio es un delito de fácil ejecución, pero de difícil investigación. La prevalencia de este delito es de 1,13%. La incidencia de este crimen está creciendo alrededor del mundo, provocando un impacto social importante por las pérdidas financieras, muertes, lesiones físicas y secuelas emoci...

  2. Es preferible morir por el fuego, en combate, que morir en casa, por el hambre: Fidel castro

    OpenAIRE

    Borba Telles, Lisieux Elaine de; Bins, Helena Dias de Castro; Barros, Alcina Juliana Soares; Escobar Córdoba, Franklin

    2012-01-01

    Antecedentes. El concepto de fuego siempre ha atraído la atención del hombre. En la literatura abundan referencias a este término, que tanto puede representar poder y pasión como terror y destrucción. El incendio es un delito de fácil ejecución, pero de difícil investigación. La prevalencia de este delito es de 1,13%. La incidencia de este crimen está creciendo alrededor del mundo, provocando un impacto social importante por las pérdidas financieras, muertes, lesiones físicas y secuelas emoci...

  3. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    OpenAIRE

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated dr...

  4. Armies sand Politics, Moscú, Pashentsev N., Evgeny, y Miniar-Beloruchev V. Constantine (coord.), Moscú, Russian Progressive Review, 2002, 398 pp.

    OpenAIRE

    Burgos, Elizabeth

    2005-01-01

    Las Fuerzas Armadas en América Latina, pese a la singularidad de su presencia en la vida política y a su peso en el seno del Estado, y, al carácter intervencionista de su acción, es un fenómeno que atrae poco a los investigadores. El debate se ha abordado, principalmente, desde el prisma de los Derechos Humanos. Sin embargo, en los últimos tiempos se observa un resuelto interés en los medios académicos por su estudio como elemento ineludible dentro del panorama político del contienente. Prueb...

  5. Estratégias de gestão coletiva de recursos naturais em assentamentos de reforma agrária da mesorregião da Mata Sul de Pernambuco-Brasil

    OpenAIRE

    Silva, Rosineide Vieira da

    2015-01-01

    Tese de Doutoramento em Gestão No decorrer da evolução e expansão econômica mundial dos últimos anos, evidenciam-se diferentes formas de articulação entre o desenvolvimento e os recursos da biodiversidade. A Zona da Mata Pernambucana já vivenciou no passado e presencia, na atualidade, processos de modernização agrária com padrões de origem nacional e internacional, que resultaram no processo de progressivo abandono das atividades agrícolas, com os antigos trabalhadores atraídos pelas novas...

  6. Atrayendo Talento: estrategias de Movilidad de los profesionales altamente cualificados en España

    OpenAIRE

    González Ramos, Ana M.

    2011-01-01

    En las últimas décadas, se ha realizado un gran esfuerzo centrado en la formación de los profesionales españoles altamente cualificados. Además, la competitividad económica y la evolución positiva de los indicadores de ciencia y la innovación tecnológica han atraído el talento extranjero. El presente artículo se centra en las estrategias protagonizadas por el personal altamente cualificado en el sistema nacional de I+D+I, así como en la adecuación de los programas de movilidad y la normativa ...

  7. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism

    OpenAIRE

    Ross, A. Catharine; Zolfaghari, Reza

    2011-01-01

    The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family—CYP26A1, CYP26B1, and CYP26C1—is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1...

  8. 4-Oxoretinol, a new natural ligand and transactivator of the retinoic acid receptors.

    OpenAIRE

    Achkar, C C; Derguini, F; Blumberg, B; Langston, A; Levin, A A; Speck, J; Evans, R M; Bolado, J; Nakanishi, K; Buck, J.; Gudas, L J

    1996-01-01

    All-trans-retinoic acid (at-RA) induces cell differentiation in a wide variety of cell types, including F9 embryonic teratocarcinoma cells, and can influence axial pattern formation during embryonic development. We now identify a novel retinoid synthetic pathway in differentiating F9 cells that results in the intracellular production of 4-oxoretinol (4-oxo-ROL) from retinol (vitamin A). Approximately 10-15% of the total retinol in the culture is metabolized to 4-hydroxyretinol and 4-oxo-ROL b...

  9. example of paclitaxel

    OpenAIRE

    Doktorovova, Slavomira; Lopes, Carla Martins; Souto, Eliana B

    2009-01-01

    Os vectores coloidais de natureza lipídica têm atraído particular atenção para o desenvolvimento de terapias mais seguras e eficazes aplicadas a várias doenças. As vantagens da utilização das nanopartículas lipídicas são exemplificadas utilizando o paclitaxel, um anticancerígeno particularmente interessante para o desenvolvimento de novas formas farmacêuticas mais adequadas para o tratamento do cancro. De facto, este fármaco apresenta problemas de insolubilidade aquosa e sérios...

  10. Novel targeted therapy for acute myeloid leukemia with a dual FLT3 and JAK2 inhibitor

    Institute of Scientific and Technical Information of China (English)

    Yin-jun LOU

    2012-01-01

    Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor.The use of all-trans retinoic acid (ATRA) and arsenic trioxide,which began from China,has resulted in revolution of the acute promyelocytic leukemia (APL) that appears curable in more than 70% of patients[1].However,the treatment regimen for nonAPL AML particularly in older patients has progressed little in the past two decades.Intensive efforts have been made toward the development of novel target agents,which are based on newfound pathophysiological events crucial for cancers.

  11. impacto na saúde oral

    OpenAIRE

    Silva, Bruna Loureiro Oliveira de Sousa e

    2012-01-01

    Os distúrbios alimentares traduzem-se em comportamentos, quer pela falta, quer pelo excesso da ingestão de alimentos O crescente aumento destes distúrbios, nomeadamente a obsessão pelos corpos magros, relaciona-se com o impacto que os media tem na sociedade, uma vez que a magreza é vista como mecanismo de atração sexual e mecanismo de integração social. Das desordens alimentares fazem parte a anorexia nervosa, a bulimia nervosa e a obesidade. Ao contrário da obesidade, a anorexia ne...

  12. Notas para reflexionar acerca de las identidades (sexuales) de varones que sociabilizan mediante internet

    OpenAIRE

    Peplo, Fernando Franco

    2013-01-01

    La sociabilidad virtual se ha transformado en una práctica habitual por parte de varones que se sienten sexualmente atraídos por otros varones porque ofrece anonimato, fluidez y la disponibilidad constante para iniciar vínculos. Estas características se tornan más relevantes en aquellas localidades pequeñas o medianas del interior del país puesto que “la discreción y la reserva” en relación a las experiencias homosexuales constituyen bienes muy preciados, en especial para aquellos sujetos que...

  13. Estudio de prefactibilidad para la creación y puesta en marcha de una empresa operadora de turismo de naturaleza en Urabá

    OpenAIRE

    Gallego Moscoso, Laura; Lizcano Alonso, Adriana del Pilar; Muñoz Zuluaga, Paula Andrea

    2013-01-01

    El Gobierno Nacional tiene clara su apuesta en materia de turismo: sofisticación de la oferta, teniendo como pilar la biodiversidad que cada año atrae miles de turistas que disfrutan de los paisajes y practican actividades en las que la naturaleza es la protagonista -- Al contexto nacional se suma la visión del Gobierno del departamento de Antioquia, plasmada en su Plan de Desarrollo Turístico, que de igual manera se enfoca en el turismo especializado -- Esto constituye una oportunidad estra...

  14. Primary Survey on Herpetofauna in Campus of Hechi University in Central Guangxi%河池学院校园两栖爬行动物初步调查

    Institute of Scientific and Technical Information of China (English)

    蒋爱伍; 粟通萍; 于家捷; 梁晓凤

    2011-01-01

    A primary survey on herpetofauna was conducted by specimen collecting and interviewing in campus of Hechi University, central Guangxi, during July 2008 to December 2009. Totally 26 species were detected in this survey. Among them, 6 species of 4 families, 1 order belonged to the class Amphibia, and 20 species of 7 families, 2 orders belonged to the class Reptilia. The dominant Amphibia is Polypedates leucomystax, and the dominant Reptilia is Rhabdphis subminiatus,Naja atra and Eumeces chinensis. 6 species of 12 snakes are vipers in the campus, and Naja atra is the most dangerous. The Amphibia depend on running water have already disappeared along with urbanization, and the species breeding or preying on the building,such as Pol y pedates leucom ystax , Naja atra and Hem idact ylus bowrin gii , can adapt the habitat of urban.%2008年7月至2009年12月,利用标本采集和访问的方法对河池学院校园内两栖爬行动物资源进行了初步的调查,共记录到两栖爬行动物26种,其中两栖动物1目4科6种,爬行动物2目7科20种.在校园中最常见的两栖动物是斑腿泛树蛙(Polypedates leucomystax),最常见的爬行动物是红脖颈槽蛇(Rhabdphissubminiatus)、舟山眼镜蛇(Naja atra)和中国石龙子(Eumeces chinensis).在校园分布的12种蛇类中,6种为毒蛇,其中舟山眼镜蛇的危害最为严重.师生在工作和学习要特别注意防止咬伤.与周边地区相比,在城市化过程中,流水型的两栖动物最容易灭绝;能利用建筑物繁殖或捕食的种类,如斑腿泛树蛙、原尾蜥虎和舟山眼镜蛇等,在城市化过程中占有较大的优势.

  15. Maduración y desove del pargo amarillo Lutjanus argentiventris (Peters, 1869) en condiciones controladas de temperatura y fotoperíodo

    OpenAIRE

    Martínez, R.A. (Raquel)

    2003-01-01

    El cultivo de peces marinos ha atraído considerable atención en la última década, experimentando un gran auge en años recientes. Esto se debe principalmente al desarrollo y optimización de la tecnología de cultivo en jaulas, como también al mejoramiento de las técnicas de producción de juveniles, lo que ha incrementado el número de especies para las cuales existen cultivos de orientación comercial. En las circunstancias actuales, para que el cultivo de peces sea rentable es necesario controla...

  16. Mujer Pagana/ Mujer Cristiana en Ad uxorem de Tertuliano

    OpenAIRE

    López Abelaira, Elena

    2016-01-01

    Desde los primeros años del cristianismo la figura de la mujer no ha pasado desapercibida para los distintos autores. Nos parece muy interesante la figura de Tertuliano, autor africano de los siglos II-III d. C. Pagano de formación y atraído por el mensaje y las vivencias de la nueva religión, pero confundido por la radicalidad que surgieron en las sectas del cristianismo. Es el primer escritor cristiano del norte de África que se ocupó ampliamente de la mujer virgen, viuda y casada. Sient...

  17. Heurísticas para localização de sensores

    OpenAIRE

    Silva, Diogo Filipe Martins Ferreira da

    2013-01-01

    Tese de mestrado em Investigação Operacional, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013 Neste trabalho é desenvolvido o algoritmo de atração, uma heurística inspirada em algoritmos evolutivos, tendo como objetivo a resolução de problemas contínuos de localização e cobertura. Numa primeira parte o problema é abordado tendo em conta uma cobertura binária, tornando o problema mais simples e a explicação das ideias chave da heurística mais clara. Depois de co...

  18. Traducción y adaptación transcultural de la escala SQLS para medir la calidad de vida en pacientes con esquizofrenia en Colombia

    OpenAIRE

    Peña Solano, Diana Marcela

    2011-01-01

    El estudio de la calidad de vida y de la sensación subjetiva de bienestar de los pacientes es un fenómeno relativamente nuevo, que ha atraído la atención de los profesionales de la salud, apenas en las tres últimas décadas. Durante 1850 y 1950, la medicina estuvo dominada por el tema de la cura de las enfermedades, mientras que el tratamiento de enfermedades crónicas, discapacitantes e incurables recibía menor atención (1). En los últimos años ésta tendencia ha cambiado. La calidad de vida...

  19. Planificación de Diferentes Clases de Aplicaciones en Entornos No Dedicados Considerando Procesadores Multicore

    OpenAIRE

    García Gutiérrez, José Ramón

    2010-01-01

    Descripció del recurs: el 27 de juny de 2011 A día de hoy es prácticamente imposible encontrar una gran institución que no disponga de un parque de ordenadores considerable, debido al alto nivel de informatización de la sociedad actual. El enorme potencial que representan estos miles de ordenadores atrae poderosamente la atención en los ámbitos científicos e industriales, generando opciones viables para su aprovechamiento. Las universidades, instituciones que históricamente se han mantenid...

  20. SÍNTESE DA PENEIRA MOLECULAR MCM-41 DERIVADA DA CINZA DA CASCA DO ARROZ

    OpenAIRE

    Renata Martins Braga; Najara Maira Teodoro; Dulce Maria de Araujo Melo; Flávia de Medeiros Aquino; Joana Maria de Farias Barros; Julio Cezar de Oliveira Freitas

    2013-01-01

    As peneiras moleculares MCM-41 têm atraído grande interesse devido as suas propriedades de alta área específica, volume e diâmetro de poros controláveis. Estes materiais são aplicados em diversos ramos da indústria química como adsorventes, suportes catalíticos e catalisadores heterogêneos em vários processos. Neste trabalho, o MCM-41 foi sintetizado a partir da cinza da casca do arroz, natural e tratada quimicamente, como fontes alternativas de sílica, denominadas CCA-MCM-41 e CCAL-MCM-41, r...

  1. Hacia un studio aspectual contrastive entre el Esloveno y el Español

    Directory of Open Access Journals (Sweden)

    Jasmina Markič

    1991-12-01

    Full Text Available El tema del aspecto verbal ha suscitado un sinfín de opiniones, reflexiones, teorías, definiciones y ha atraído a numerosos lingüistas detodas las corrientes. A pesar de que se hayan propuesto últimamente diversas soluciones al problema y se haya buscado una metodología para estudiar el aspecto, en la mayoría de los casos no se trata de investigaciones generales sobre el aspecto como categoría lingüística universal sino de estudios del aspecto en determinadas lenguas.

  2. El multilateralismo como intervencionismo. Estados Unidos y la Sociedad de Naciones en América Latina (1930-1946)

    OpenAIRE

    Sánchez Román, José Antonio

    2015-01-01

    Este artículo analiza una dinámica de intervenciones de Estados Unidos en América Latina que no ha atraído suficientemente la atención de los historiadores. En los años treinta y cuarenta, cuando Europa se hundía en una nueva confrontación bélica, ciertos sectores del gobierno y del mundo empresarial norteamericano intentaron articular una nueva relación con los países del continente basada en una propuesta de multilateralismo que se había configurado dentro de la Sociedad de Naciones (SN). E...

  3. Prácticas de innovación abierta en PYMEs : El caso del auto superdeportivo mexicano VUHL

    OpenAIRE

    Ramirez-Portilla, Andres; Cagno, Enrico; Brown, Terrence

    2014-01-01

    Es bien sabido que la innovación impulsa el desarrollo de las organizaciones de diferentes tamaños e industrias. Mientras para las grandes empresas es relativamente fácil innovar debido a sus recursos, en el caso de las pequeñas y medianas empresas (PYMEs) el escenario es más complicado. Sin embargo, existen modelos para gestionar la innovación que han probado ser útiles para apoyar a varios tipos de empresas. La Innovación Abierta (Open Innovation) es uno de estos modelos que ha atraído la a...

  4. Revirando A Virada

    OpenAIRE

    Oliveira, Rosenilton S.

    2014-01-01

    "Venha viver a Virada!". Anunciava o slogan da Virada Cultural. Em 2013, o evento que reúne atrações culturais que vão da música erudita ao cinema pornô, efetivou sua nona edição e, em pouco mais de 24 horas, reuniu no centro de São Paulo e em alguns outros pontos da cidade, milhares de pessoas. Alguns dos pesquisadores do Laboratório de Antropologia Urbana da Universidade de São Paulo (NAU/FFLCH-USP), mais uma vez estiveram presentes para acompanhar estes citadinos em suas deambulações em me...

  5. Breeding biology of two sympatric coots with contrasting conservation status

    OpenAIRE

    Varo, Nico

    2008-01-01

    Capsule: Red-knobbed Coots Fulica cristata and Common Coots Fulica atra have similar breeding biology except in chick survival, which was significantly lower in Red-knobbed Coots. Aims: To provide information on the breeding biology of Red-knobbed Coots in Spain and to compare this with similar data for Common Coots. Methods: During two consecutive breeding seasons, clutch size, egg size, brood size and chick survival of Red-knobbed and Common Coots were studied in nearly all of the lagoons i...

  6. The role of all-trans retinoic acid in the biology of Foxp3+ regulatory T cells

    OpenAIRE

    Liu, Zhong-Min; Wang, Kun-Peng; Ma, Jilin; Guo Zheng, Song

    2015-01-01

    Regulatory T (Treg) cells are necessary for immune system homeostasis and the prevention of autoimmune diseases. Foxp3 is specifically expressed in Treg cells and plays a key role in their differentiation and function. Foxp3+ Treg cells are consisted of naturally occurring, thymus-derived Treg (nTreg) and peripheral-induced Treg (iTreg) cells that may have different functional characteristics or synergistic roles. All-trans retinoic acid (atRA), a vitamin A metabolite, regulates a wide range ...

  7. Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using ortho-Diisocyanoarenes as Radical Acceptors.

    Science.gov (United States)

    Leifert, Dirk; Studer, Armido

    2016-09-12

    A simple method for the preparation of functionalized quinoxalines is reported. Starting from readily accessible ortho-diisocyanoarenes and (perfluoro)alkyl iodides, the quinoxaline core is constructed during (perfluoro)alkylation by atom transfer radical addition (ATRA), resulting in 2-iodo-3-(perfluoro)alkylquinoxalines. The radical cascades are readily initiated either with visible light or by using α,α'-azobisisobutyronitrile (AIBN). The heteroarene products are obtained in high yields (up to 94 %), and the method can be readily scaled up. Useful follow-up chemistry documents the value of the novel radical quinoxaline synthesis.

  8. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    OpenAIRE

    Navneet Gill; Bijjem, Krishna Reddy V.; Sharma, Pyare L

    2013-01-01

    Objective: In this study, we investigated the role of peroxisome proliferator-activated receptors (PPAR)-β/δ receptors in carrageenan-induced inflammation and in the anti-inflammatory effects of all-trans retinoic acid (ATRA). Materials and Methods: The λ-carrageenan (0.1 ml of 1% w/v) was injected into intra-plantar (i.pl.) region of the hind paw to produce acute inflammation. Paw volume was measured by using the mercury plethysmography. Further, mechanical and thermal hyperalgesia (TH) ...

  9. Propiedades nutraceúticas del licopeno Nutraceutical properties of lycopene

    OpenAIRE

    Krzysztof N Waliszewski; Gabriela Blasco

    2010-01-01

    Las recomendaciones dietarias en los últimos años proponen el incremento del consumo de alimentos que contienen fitoquímicos, ya que éstos proveen efectos benéficos para la salud humana y juegan un papel importante en la prevención de enfermedades crónicas. El licopeno, carotenoide responsable del color rojo de los tomates, ha atraído la atención debido a sus propiedades biológicas y fisicoquímicas en la prevención de enfermedades crónicas como cáncer, enfermedades cardiovasculares y neurodeg...

  10. Produção e desenvolvimento da cultura de Physalis L. submetida a diferentes níveis de condutividade elétrica da solução nutritiva Production and development of culture of Physalis L. subjected to different levels of electrical conductivity of nutrient solution

    OpenAIRE

    Alessandra Ianckievicz; Hideaki Wilson Takahashi; Gustavo Adolfo de Freitas Fregonezi; Fernando Kikuchi Rodini

    2013-01-01

    Physalis peruviana L., muito conhecida na Colômbia e originaria dos Andes Sul-americanos, tem atraído alguns produtores aqui no Brasil por produzir uma fruta com alto valor de mercado. Como se trata de uma cultura adaptada a algumas regiões brasileiras, o fornecimento de nutrientes é um dos aspectos importantes que precisa ser desenvolvido para aumentar a produtividade. O trabalho objetivou estabelecer as faixas ideais de concentração de nutrientes, utilizando a condutividade elétrica da solu...

  11. Como es arriba es abajo: Simbolismo de los astros en Hermetismo y astrología

    OpenAIRE

    Aznar, Susana

    2016-01-01

    La cultura forma nuestra cosmovisio¿n de la realidad. Actualmente nuestra cultura esta¿ repleta de si¿mbolos e ima¿genes que de forma silenciosa transmiten sus mensajes a nuestro inconsciente. Entre todos compartimos una visio¿n global, ya que todos somos ba¿sicamente lo mismo: Seres humanos. Nuestra psique inconsciente presenta unos arquetipos que son presentes en todo el mundo, formando lo que se conoce como inconsciente colectivo. Mirando atra¿s en la historia nos damos cuenta que mucho...

  12. La educación inclusiva frente a las desigualdades sociales: un estado de la cuestion y algunas reflexiones geograficas

    OpenAIRE

    Rambla, Francesc Xavier, 1966-; Tarabini-Castellani, Aina; Ferrer i Julià, Ferran; Verger, Antoni

    2008-01-01

    Este artículo establece un estado de la cuestión e la educación inclusiva en el mundo y sugiere algunas reflexiones al respecto. El primer apartado recuerda las conexiones ineludibles entre las preocupaciones educativas por la educación inclusiva y las preocupaciones más generales por la desigualdad. El segundo consigna los criterios de búsqueda de las publicaciones académicas, y observa dos grandes temas en sus contenidos: sobre todo, el cambio interno de las escuelas atrae las miradas, pero...

  13. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    OpenAIRE

    Yonal Ipek; Dogru Hulya; Aktan Melih

    2012-01-01

    Acute promyelocytic leukemia (APL) is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa) locus on chromosome 17, the great majority of which is t(15; 17)(q24.1; q21.1) (Collins (1998), Melnick and Licht (1999), and Grimwade (1999)). Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA) is a sub...

  14. Coerência espectral do eletrencefalograma em pacientes submetidos a transposição tendinosa: estudo pré e pós-operatório EEG spectral coherence at patients submitted to tendon transfer surgery: study pre and post surgery

    OpenAIRE

    Julio Guilherme Silva; Irocy Guedes Knackfuss; Cláudio Elidio Portella; Victor Hugo do Vale Bastos; Dionis de Castro Dutra Machado; Luis Basile; Roberto Piedade; Pedro Ribeiro

    2006-01-01

    A transferência tendinosa do músculo tibial posterior é intervenção cirúrgica bastante utilizada na ortopedia para correção do pé caído por seqüela de hanseníase. Poucos modelos propuseram investigações mais significativas sobre os fenômenos plásticos cerebrais nas transferências tendinosas. O presente estudo teve como objetivo analisar a coerência espectral (CE) na Eletroencefalografia (EEG) em pacientes submetidos a transferência do tendão do tibial posterior pela técnica de Srinivasan atra...

  15. La inserción de las ciudades del Mediterráneo español en el espacio de la globalización a través de la red de empresas multinacionales: el caso de la ciudad de Valencia

    OpenAIRE

    Salom Carrasco, Julia

    2013-01-01

    El objetivo de la comunicación es definir la posición de las ciudades del Mediterráneo español en las redes económicas mundiales a partir del análisis de las relaciones de propiedad y filiación de las empresas multinacionales ubicadas en ellas, así como caracterizar el alcance espacial y la especialización sectorial de los enlaces que las conectan con dichas redes. A nivel internacional, el aumento de la globalización ha atraído la atención sobre los conceptos de “world cities” (Hall, ...

  16. La organización de los oficios en al-Andalus a través de los manuales de "hisba"

    OpenAIRE

    García Sanjuán, Alejandro

    1997-01-01

    Como podrá comprobarse a lo largo del presente artículo, la organización corporativa de los oficios en el islam medieval ha sido objeto de una amplia polémica entre diversos autores, en buena medida provocada por la falta de acuerdo respecto al concepto de “corporación profesional”. No obstante, en lo que se refiere al caso específico de al-Andalus, este tema no ha atraído la atención que, a nuestro juicio, se merece. El objetivo de estudio es, por ello, profundizar en este asunto y revisar l...

  17. Determination of element composition of three lichens and their distribution in King George Island, Antarctica

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cross-section slices of Usnea antarctica Du Rietz, Usnea aurantiaco-atra (Jacq.) Bory. and Cladonia sp. at upper, middle and basal positions were prepared, respectively. The element composition and relative content were determined by SEM and EDS at the surface, intermediate and inner layers in each slice, respectively. The result indicated that the composition of element is mostly same in these lichens. The relative content of Al, Si, K and Ca elements is high, and P is close at each position. The result is of benefit to study the structure and physiological characteristics of lichens, and to analyze geological environment in Antarctica.

  18. Investigation of the Role of All-Trans Retinoid Acid in Inducing Differentiation of Retinoblastoma in Vivo%维甲酸诱导分化视网膜母细胞瘤的机理研究

    Institute of Scientific and Technical Information of China (English)

    王艳; 高解春; 董岿然; 陈莲; 王舒宜

    2011-01-01

    Objective To investigate the role and possible mechanism of all-trans retinoid acid in inducing differentiation of retinoblastoma in nude mice. Methods SO-RB50 suspense cell mixture was injected into bilateral armpits of male nude mice, and model of retinoblastoma nude mice was established. The size and weight of tumors were observed twice every week ,tumors' structure were recorded under microscope and electro-microscope, tumors' DNA index was calculated, relative quantities of gene CyclinDl ,CDK4 and ICAM-1 were measured by trans-transcription polymerase chain reaction and fluorescent quantity. Results At the end of the experiment, average tumor weight of ATRA group( 2. 750± 0. 302 ) g was lower than that of control group ( 7.150 ±1. 228 ) g( P = 0.008 ), and average tumor weight of Vitamin A deficient group( 11. 483 ± 2. 271 ) g( P = 0. 003 ). Under microscope, necrosis without inflammation was found in retinoblastoma cells in ATRA group, cells in control group appeared the same as those in original xenograft, retinoblastom cells in Vitamin A deficient group had a higher nuclear-plasma ratio than that of control group. Under electro-microscope, retinoblastoma cells in ATRA group contained swelled and bubble-like mitochondrion and much less ribosomes than those in control group. Cells in Vitamin A deficient group contained more free ribosomes and less lysosomes in the plasma than those in control group. Trans-transcription PCR and fluorescent quantity showed the relative quantity of CyclinD1 was the lowest in ATRA group( P =0.012) and highest in Vitamin A deficient group( P =0.017 ) ;the relative quantity of CDK4 was lowest in ATRA group(P =0.010) and highest in Vitamin A deficient group( P =0. 029). There was no statistical significance in ICAM-1 between ATRA group and control group(P =0.071 ) or between Vitamin A deficient group and control group ( P= 0.083 ). Conclusion The growth of retinoblastoma xenograft in ATRA group was restrained by ATRA, and Vitamin

  19. El vínculo entre sexualidad y violencia en el teatro de Angélica Liddell

    OpenAIRE

    Topolska, Ewelina Maria

    2014-01-01

    Angélica Liddell’s surge to (relative) fame in recent years (a process which began in 2000, peaking around 2008/09) resulted in an increasing number of articles being published about her theatre, not to mention a significant number of interviews she gave for the Spanish and international press. There is also a doctoral thesis by Ana Vidal Egea concerning Atra Bilis’ (the name of Liddell’s group) work. However, no existing study engaged in detailed analysis of the artist’s theatrical productio...

  20. Padronização da técnica imunoenzimática do ELISA de captura, no sistema avidina-biotina para a identificação de sangue ingerido por Lutzomyia (Lutzomyia) longipalpis (Lutz & Neiva, 1912) Enzyme-linked Immunosorbent Assay biotin/avidin method standardization, for identification of Lutzomyia (Lutzomyia) longipalpis bloodmeals (Lutz & Neiva, 1912)

    OpenAIRE

    Ana Maria Marassá; Cleide Aschenbrenner Consales; Eunice Aparecida Bianchi Galati

    2004-01-01

    A identificação de sangue ingerido pelos insetos é um importante parâmetro para elucidar aspectos ligados à transmissão de zoonoses, dentre elas, as leishmanioses. Dos métodos empregados para esclarecer a atração de vetores por animais que possam atuar como reservatórios dessas parasitoses, destacam-se os imunológicos. O estudo teve como objetivo, padronizar a técnica imunoenzimática de captura e titular amostras de sangue ingerido em fêmeas de flebotomíneos ingurgitadas de Lutzomyia longipal...

  1. Guerra, psicología social y derechos humanos: procesos de gubernamentalidad y estado de excepción policial en torno al "15m", Catalunya 2011-2012

    OpenAIRE

    Benedicto Salmerón, Rubén A.

    2015-01-01

    Esta tesis analiza la posible correspondencia de la actuación policial-gubernamental sobre las movilizaciones sociales en torno al ‘15M' en Catalunya con marcos generales estratégicos de pensamiento de guerra, en donde no se distingue la paz de la guerra y la acción sobre las variables psicosociales desempeña un papel clave y transversal. En torno al 15 de mayo de 2011, se produjo en el Estado español una ola de movilizaciones sociales en protesta por la situación de profundas crisis que atra...

  2. Cuatro viajes en la literatura del antiguo Egipto (2ª ed)

    OpenAIRE

    Galán Allué, José Manuel

    2000-01-01

    Cuatro Viajes pretende servir de introducción a la literatura del antiguo Egipto a todos los estudiosos de esta milenaria cultura, así como a quienes disfrutan y se interesan por la literatura en general. Es inevitable que en un primer impulso el público se sienta atraído por la grandeza de los monumentos y la belleza de los relieves y pinturas que los decoran, además de por la riqueza de los muy variados objetos de la cultura material que nos ha legado el antiguo Egipto. Sin embargo, es a tr...

  3. Empenhamento organizacional nos trabalhadores temporários

    OpenAIRE

    Oliveira, Eduardo André da Silva

    2009-01-01

    Dissertação de mestrado em Gestão de Recursos Humanos O estudo do empenhamento organizacional tem concitado o interesse de académicos e profissionais da gestão de recursos humanos. Segundo Swailes (2000), torna-se difícil encontrar na literatura organizacional dos últimos trinta anos, um tópico que tenha atraído tanta atenção como o empenhamento. Aos práticos, interessa a sua compreensão para instilar e manter uma cultura de empenhamento na organização. Este interesse recrudesc...

  4. The effectiveness of environmental enrichment in two captive south-african fur seals (Arctocephalus pusillus pusillus)

    OpenAIRE

    Lã, Mariana Vieira, 1988-

    2012-01-01

    Tese de mestrado. Biologia (Biologia da Conservação). Universidade de Lisboa, Faculdade de Ciências, 2012 A otária Sul-Africana (Arctocephalus pusillus pusillus) é uma subespécie encontrada em zoos por todo o mundo, que se adapta geralmente bem a condições de cativeiro, reproduzindo-se com frequência. Não se encontra ameaçada pelo que, tal como a maioria dos pinípedes, é mantida em zoos principalmente por ser emblemática e ter um papel importante na atração e sensibilização dos visitantes....

  5. "Las bandas sonoras como base de la audición activa: experiencias educativas para el desarrollo musical infantil" [Music for films as a basis of active listening: educational experiences to child music development

    OpenAIRE

    María del Valle de Moya Martínez; Juan Rafael Hernández Bravo; José Antonio Hernández Bravo

    2011-01-01

    RESUMEN:La Educación Musical contribuye desde edades tempranas a la adquisición paulatina de aprendizajes en el marco de una acción educativa sistematizada. La música favorece el intercambio comunicativo entre los niños/as, así como el desarrollo de unas funciones psicológicas básicas como la atención, la memoria y la percepción visual y auditiva. En la etapa de Educación Infantil, los niños/as se sienten atraídos por los sonidos, las canciones, el movimiento, las posibilidades expresivas de ...

  6. Turismo, Autenticidade e Cultura Urbana: percurso teórico, com paragens breves em Évora e Coimbra

    OpenAIRE

    Fortuna, Carlos

    1995-01-01

    o turismom é um fenómeno que tem atraído um notável esforço de análise sociológica nos últimos anos. Este texto comenta grande parte desta sociologia do turismo nomeadamente a que diz mais directamente respeito ao turismo cultural e urbano. Ao mesmo tempo, sugerem-se algumas linhas de interpretação do fenómeno, sob a influência de outras áreas do pensamento sociológico contemporâneo. Assim, sugere-se que o estudo do turismo seja feito, à luz de (1) transfor...

  7. Italian municipalities' NPFM reforms: an institutional theory perspective

    OpenAIRE

    Elisabetta Reginato; Isabella Fadda; Aldo Pavan

    2010-01-01

    Entender las razones del fracaso o el éxito de las reformas impulsada por el NPFM es un tema que ha atraído recientemente la atención de la literatura sobre la gestión del sector público. Sobre la base de un estudio de caso realizado en el gobierno local italiano, la investigación analiza el estado de real aplicación de las reformas mencionadas anteriormente, y contribuye al debate teórico sobre las razones que explican las diferencias entre los cambios formales y sustanciales en la administr...

  8. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    Directory of Open Access Journals (Sweden)

    A. Sanz Miguel

    2006-04-01

    Full Text Available Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO en recaídas de pacientes con leucemia promielocítica (LPA, el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH.

  9. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    OpenAIRE

    A. Sanz Miguel

    2006-01-01

    Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO) en recaídas de pacientes con leucemia promielocítica (LPA), el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA) y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH).

  10. CONTRIBUTIONS TO THE KNOWLEDGE OF THE SPECIES OF BEETLES (INSECTA: COLEOPTERA FROM WHEAT CROP

    Directory of Open Access Journals (Sweden)

    Mihai Tălmaciu

    2016-07-01

    Full Text Available This paper presents the species of beetles (Insecta: Coleoptera between in wheat crops from Tişiţa, in Vrancea county. The observations were made in a crop of wheat in 2013, who were placed the soil traps type Barber, during the two months, May and June. It was used three variants: • Variant 1 - consumption wheat untreated • Variant 2 - consumption wheat treaty • Variant 3 - treated wheat seed The gathering of samples from the traps was done periodically, every 12-15 days. The most species frequent gathered was: Pentodon idiota, Epicometis hirta, Opatrum sabulosum, Phyllotreta atra, Phyllotreta nemorum, Tanymecus dilaticollis.

  11. Del deseo al clímax : represión y expresión de la temática de sexualidad y suicidio en la literatura femenina anglonorteamericana de los siglos XIX y XX

    OpenAIRE

    Cortés Vieco, Francisco José

    2013-01-01

    La sexualidad y el suicidio son dos intrincados fenómenos físico-socio-psicológicos que, aunque determinen la existencia, el destino y la naturaleza intrínseca del individuo, se han entretejido tradicionalmente con tabú, estigma, silencio, locura, pecado y mal, hasta caer en el olvido o el más absoluto ostracismo por mandato de hegemónicos discursos oficiales. No obstante, han atraído y despertado la curiosidad de artistas y literatos a lo largo de nuestra historia, transfigurándose incluso e...

  12. ESTUDIO DE ALGUNOS GÉNEROS MICROBIANOS ASOCIADOS A DIFERENTES VARIEDADES DE TRIGO (Triticum aestivum L. EN SUELO FERRALÍTICO ROJO

    Directory of Open Access Journals (Sweden)

    Annia Hernández

    2002-01-01

    Full Text Available Se estudiaron los géneros bacterianos predominantes en la rizosfera de cuatro variedades de trigo (Triticum aestivum L. crecido en un suelo Ferralítico Rojo. También se evaluó la quimioatracción de algunas rizobacterias hacia los exudados radicales de este cultivo. Se utilizó el Modelo Espermosférico para el aislamiento y los tubos colectores y la cámara de quimiotaxis modificada para la evaluación del efecto quimiotáctico de los exudados radicales. Los resultados obtenidos demostraron que en las variedades Gang y Caeté, Pseudomonas es la población dominante, siendo Pseudomonas (Burkholderia cepacia la especie más fuertemente atraída por los exudados radicales a los 14 días y 40 minutos de exposición. En las variedades Culiacam y Antisama, es el género Azospirillum el predominante en la rizosfera, siendo esta especie la más fuertemente atraída por los exudados radicales a los 14 días y 60 minutos de exposición. Esta investigación permite la aplicación de biofertilizantes a base de los géneros microbianos predominantes en la rizosfera del trigo, potenciando su actividad sin alterar la biología del suelo.

  13. Acute promyelocytic leukemia: An experience from a tertiary care centre in north India

    Directory of Open Access Journals (Sweden)

    J Bajpai

    2011-01-01

    Full Text Available Background: There are very limited data reported about acute promyelocytic leukemia (APL from developing countries. We reviewed the clinical course and treatment outcome of APL patients treated at our center. Materials and Methods: Between January 1997 and December 2007, 33 patients with APL received induction therapy using ATRA + daunorubicin (n = 26, As = 26, As2O3 (n = 4 or daunorubicin + cytosar ( n = 3. Results: Median age was 30 years with a male to female ratio of 1.68. Twenty seven patients (82% achieved CR. Complications during induction therapy were febrile neutropenia (33%, ATRA syndrome (30%, bleeding (58%, and diarrhea in (6% patients. During induction and follow up, 8 (24.24% patients died, 6 (18.18% during induction, 1 (3% during maintenance, and 1 (3% after relapse. Median OS is 128 months while median EFS is 61 months. Four patients relapsed at a median time of 61 months. At the time of censoring, 25 patients were alive at a median follow up of 13 months (range 0.6 -127 months; 21 in CR1, 3 in CR2, 1 in CR3. Comparisons among the risk groups (CR and relapse rate and survival statistics were not statistically significant. Conclusions: APL is a highly curable malignancy. Our results confirm the findings of the published literature from larger cooperative studies from the West. We may further improve outcome with quicker diagnosis and more efficient supportive care system.

  14. Differentiation Therapy of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Elzbieta Gocek

    2011-05-01

    Full Text Available Acute Myeloid Leukemia (AML is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA, which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL in which a PML-RARA fusion protein is generated by a t(15;17(q22;q12 chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS. Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  15. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    Science.gov (United States)

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated drugs, such as camptothecin, imazalil, itraconazole, hygromycin, and 4-nitroquinoline oxide. We also verified the relative transcript levels of the Atr genes in the A. nidulans imazalil-resistant mutants. These genes displayed a very complex pattern in different ima genetic backgrounds. The imaB mutant has higher basal transcript levels of AtrB and -D than those of the wild-type strain. The levels of these two genes are comparable when the imaB mutant is grown in the presence and absence of imazalil. The imaC, -D, and -H mutants have higher basal levels of AtrA than that of the wild type. The same behavior is observed for the relative transcript levels of AtrB in the imaG mutant background. PMID:11872487

  16. Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Ikezoe, Takayuki

    2014-07-01

    Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

  17. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.

    Science.gov (United States)

    Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H; Xia, Menghang

    2016-04-01

    In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling. PMID:26820057

  18. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  19. Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji.

    Science.gov (United States)

    Eastwood, Erin K; López, Elora H; Drew, Joshua A

    2016-01-01

    Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical. PMID:26805954

  20. Experimental study of retinoic acid on improving iodide uptake in MCF-7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    FU Hong-Liang; WU Jing-Chuan; DU Xue-Liang; LI Jia-Ning; WU Zhen; ZOU Ren-Jian

    2005-01-01

    The study aims to investigate the effect of retinoic acid on the iodide uptake of MCF-7 cells and its mechanism. The iodide uptake and expression of hNIS(human sodium/iodide symporter)mRNA in the breast cancer MCF-7 cells were compared individually before and after the intervention of all-trans retinoic acid (ATRA) with the iodide uptake assay and RT-PCR. The following results are obtained: (1) when treated with all-trans retinoic acid in the concentration of 1.0 μmol/L, the capacity of iodide uptake of MCF-7 cells reached about 1.5 times of the basal state; (2) 12 h after the intervention of 1.0 μmol/L ATRA, the hNISmRNA expression of the MCF-7 cells reached maximum. The study shows that all-trans retinoic acid has the effect to improve the iodide uptake of the MCF-7 cells and this effect may result from its up-regulation of the hNISmRNA expression.

  1. All-Trans Retinoic Acid Induces Expression of a Novel Intergenic Long Noncoding RNA in Adult rat Primary Hippocampal Neurons.

    Science.gov (United States)

    Kour, Sukhleen; Rath, Pramod C

    2016-02-01

    Around 90% of the mammalian genome undergoes pervasive transcription into various types of small and long regulatory noncoding RNAs, whereas only ∼ 1.5% codes for proteins. Long noncoding RNAs (lncRNAs) constitute diverse classes of sense- and antisense transcripts that are abundantly expressed in the mammalian central nervous system (CNS) in cell type- and developmental stage-specific manners. They are implicated in brain development, differentiation, neuronal plasticity, and other cognitive functions. Mammalian brain requires the vitamin A metabolite all-trans retinoic acid (atRA) for its normal development, differentiation, and cell-fate determination. However, its role in adult brain function is less understood. Here, we report atRA-mediated transcriptional upregulation of endogenous expression of a novel long intergenic noncoding RNA-rat brain expressed (LINC-RBE) in cultured primary hippocampal neurons from adult rat. We have previously reported LINC-RBE as an intergenic, simple repeat sequence containing lncRNA highly expressed in the rat brain. This is a first-time report of involvement of atRA in transcriptional upregulation of lncRNA expression in rat hippocampal neurons. Therefore, it may be involved in regulation of brain function and disease. PMID:26572536

  2. Resposta de fêmeas de Encarsia formosa Gahan (Hymenoptera: Aphelinidae aos odores do hospedeiro e da planta-hospedeira em olfatômetro de quatro vias Response of female Encarsia formosa Gahan (Hymenoptera: Aphelinidae to host and plant-host odors

    Directory of Open Access Journals (Sweden)

    Kátia Maria Medeiros de Siqueira

    2003-01-01

    Full Text Available A crescente importância da mosca-branca Bemisia tabaci raça B (Hemiptera: Aleyrodidae como praga agrícola tem incentivado a busca de inimigos naturais que possam ser utilizados em programas de controle biológico. Estudou-se a atração de fêmeas de Encarsia formosa (Hymenoptera: Aphelinidae aos odores emanados pelo seu hospedeiro - a mosca-branca B. tabaci raça B - em plantas de tomate, em olfatômetro de quatro vias. O parasitóide não apresentou atração aos odores da planta de tomate nem ao complexo planta de tomate-ninfas de B. tabaci.The increasing importance of the whitefly Bemisia tabaci race B (Hemiptera: Aleyrodidae as one of the major agricultural pest of this century, has resulted in a search for natural enemies that can be used in biological control programs. The response of naive females of Encarsia formosa (Hymenoptera: Aphelinidaeto volatiles from its hostspecies: insect (B. tabacci race B and plant (Lycopersicom esculentum Mill. were tested using 4-nose olfactometre. Parasitoid was not attracted by neither or insect hostspecies volatile.

  3. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    Science.gov (United States)

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR.

  4. Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphomainan HIV-infected patient

    Directory of Open Access Journals (Sweden)

    Boban A

    2009-01-01

    Full Text Available Abstract The occurrence of acute promyelocytic leukemia (APL in HIV-infected patients has been reported in only five cases. Due to a very small number of reported HIV/APL patients who have been treated with different therapies with the variable outcome, the prognosis of APL in the setting of the HIV-infection is unclear. Here, we report a case of an HIV-patient who developed APL and upon treatment entered a complete remission. A 25-years old male patient was diagnosed with HIV-infection in 1996, but remained untreated. In 2004, the patient was diagnosed with primary central nervous system lymphoma. We treated the patient with antiretroviral therapy and whole-brain irradiation, resulting in complete remission of the lymphoma. In 2006, prompted by a sudden neutropenia, we carried out a set of diagnostic procedures, revealing APL. Induction therapy consisted of standard treatment with all-trans-retinoic-acid (ATRA and idarubicin. Subsequent cytological and molecular analysis of bone marrow demonstrated complete hematological and molecular remission. Due to the poor general condition, consolidation treatment with ATRA was given in March and April 2007. The last follow-up 14 months later, showed sustained molecular APL remission. In conclusion, we demonstrated that a complete molecular APL remission in an HIV-patient was achieved by using reduced-intensity treatment.

  5. 4-Hydroxybenzyl modification of the highly teratogenic retinoid, 4-[(1E)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB), yields a compound that induces apoptosis in breast cancer cells and shows reduced teratogenicity.

    Science.gov (United States)

    Anding, Allyson L; Nieves, Nirca J; Abzianidze, Victoria V; Collins, Michael D; Curley, Robert W; Clagett-Dame, Margaret

    2011-11-21

    Retinoids are a class of compounds with structural similarity to vitamin A. These compounds inhibit the proliferation of many cancer cell lines but have had limited medical application as they are often toxic at therapeutic levels. Efforts to synthesize retinoids with a greater therapeutic index have met with limited success. 4-[(1E)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB) is one of the most biologically active all-trans-retinoic acid (atRA) analogues and is highly teratogenic. In this study, we show that modification of the TTNPB carboxyl group with an N-(4-hydroxyphenyl)amido (4HPTTNPB) or a 4-hydroxybenzyl (4HBTTNPB) group changes the activity of the compound in cell culture and in vivo. Unlike TTNPB, both compounds induce apoptosis in cancer cells and bind poorly to the retinoic acid receptors (RARs). Like the similarly modified all-trans-retinoic acid (atRA) analogues N-(4-hydroxyphenyl)retinamide (4-HPR/fenretinide) and 4-hydroxybenzylretinone (4-HBR), 4HBTTNPB is a potent activator of components of the ER stress pathway. The amide-linked analogue, 4HPTTNPB, is less toxic to developing embryos than the parent TTNPB, and most significantly, the 4-hydroxybenzyl-modified compound (4HBTTNPB) that cannot be hydrolyzed in vivo to the parent TTNPB compound is nearly devoid of teratogenic liability. PMID:21939267

  6. Identification of Tumor Progression-Related Genes in Astrocytoma cell Lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Chao You; Yangyun Han

    2008-01-01

    OBJECTIVE To identify progression-related genes that lead to astrocytoma progression from a low to a high grade by analyzing the gene expression profiles from different tumor grades, and all-trans retinoic acid-treated astrocytoma cell lines.METHODS In this study, all-trans retinoic acid(ATRA) was used to induce differentiation of SHG-44 cells.Then,by using a cDNA microarray, we compared gene expression profiling in different grades of astrocytoma cell lines(CHG-5,WHo Grade II and SHG-44,WHO Grade IV)and in ATRA-induced differentiation in SHG-44 cells.A panel of overlapped genes that might be related to tumor progression was identified,and the cell line individual variation was avoided as well. RESUIJTS In the 31 overlapped genes,the stable over-expression of MDM2 and UGB as well as the repression of SOD2,G3BP, and CSTB in parental SHG-44 ceils was observed and their possible roles in tumor progression were discussed.Moreover, validation of some differentially expressed genes was confirmed by Northern blots.CONCLUSl0N The overlapped genes reported in this study might relate to progression of astrocytoma.Further study of progression-related genes may be helpful to explore the genetic pathways that are involved in astrocytoma progress from a low to a high grade.

  7. Parasitism of Trombidium brevimanum larvae on agrobiont linyphiid spiders from Germany.

    Science.gov (United States)

    Tomić, Vladimir; Mąkol, Joanna; Stamenković, Srdjan; Büchs, Wolfgang; Prescher, Sabine; Sivčev, Ivan; Graora, Draga; Sivčev, Lazar; Gotlin-Čuljak, Tatjana; Dudić, Boris

    2015-08-01

    An experiment on three differently-managed agricultural fields in Ahlum, Germany, which aimed at establishing the impact of different management systems on the biodiversity of predators and decomposers, yielded a significant number of spiders parasitized by larvae of Trombidium brevimanum (Actinotrichida, Parasitengona, Trombidiidae). Spider data from the whole sampling period (September 2010-July 2012), indicated that ectoparasitic larvae were recorded only on spiders in pitfall traps in the period of June-July 2011. In this period, only eight species of Linyphiidae--out of 42 species assigned to nine spider families recorded from the study area--were parasitized by mites; considerable levels of parasitism were recorded on Erigone atra, E. dentipalpis, and Oedothorax apicatus. The highest prevalence of parasitism was recorded on the organic field for E. atra (29%), while on the integrated and conventional fields significantly fewer parasitized spiders were observed. The preferred attachment sites on the spider host were regions with softer cuticle, especially regions on the carapace and on the abdomen, adjacent to the pedicel.

  8. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    Science.gov (United States)

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. PMID:26984756

  9. All-trans retinoic acid prevents the development of type 1 diabetes by affecting the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine diabetes model.

    Science.gov (United States)

    Wang, Y; Zhong, Y J; Wang, Y Y; Xing, J; Wang, Z M

    2016-01-01

    The aim of this study was to explore the molecular mechanism by which all-trans retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice were randomly assigned to three groups: prevention group [N = 20; mice received 10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5 days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then citrate buffer for 5 days). Blood glucose was measured using blood glucose test strips and serum insulin was measured by radioimmunoassay. Islets cell morphology was assessed by microscopy and ELISA was used to measure the serum levels of interferon gamma (IFN-γ) and interleukin 4 (IL- 4). In the prevention group, blood sugar levels were found to be reduced and serum insulin levels increased compared with the levels in the diabetic group (P levels of IFN-γ and increase the levels of IL-4 as well as the IFN-γ/IL-4 ratio in STZ-treated animals (P levels and increasing IL-4 levels. PMID:27050967

  10. Marketing vivencial: o caso de eventos musicais no shopping.

    Directory of Open Access Journals (Sweden)

    Ana Akemi Ikeda

    2005-12-01

    Full Text Available À medida que o mercado de shopping centers vem crescendo no Brasil e tornando-se cada vez mais competitivo, gerar fluxo de freqüentadores torna-se uma tarefa, cada vez mais, desafiadora. Diante deste cenário, o objetivo neste artigo é estudar a experiência proporcionada por eventos musicais em shopping. Para isso, além de pesquisa bibliográfica sobre o assunto, foi analisado um projeto de shows musicais realizado pelo Shopping Anália Franco, em São Paulo, que visava a melhorar a atração de visitantes, permanência do público no local e impacto nas vendas. O trabalho foi complementado com uma pesquisa de campo com os freqüentadores dos shows musicais. Os resultados mostraram que esse tipo de experiência pode beneficiar o estabelecimento em termos de maior simpatia e satisfação do público, melhoria de imagem, atração de novos consumidores, aumento do fluxo de visitantes e do volume de vendas.

  11. Retinoids and nuclear retinoid receptors in white and brown adipose tissues: physiopathologic aspects.

    Science.gov (United States)

    Flajollet, Sébastien; Staels, Bart; Lefebvre, Philippe

    2013-08-01

    Vitamin A, ingested either as retinol or β-carotene from animal- or plant-derived foods respectively, is a nutrient essential for many biological functions such as embryonic development, vision, immune response, tissue remodeling, and metabolism. Its main active metabolite is all trans-retinoic acid (atRA), which regulates gene expression through the activation of α, β, and γ isotypes of the nuclear atRA receptor (RAR). More recently, retinol derivatives were also shown to control the RAR activity, enlightening the interplay between vitamin A metabolism and RAR-mediated transcriptional control. The white and brown adipose tissues regulate the energy homeostasis by providing dynamic fatty acid storing and oxidizing capacities to the organism, in connection with the other fatty acid-consuming tissues. This concerted interorgan response to fatty acid fluxes is orchestrated, in part, by the endocrine activity of the adipose tissue depots. The adipose tissues are also sites for synthesizing and storing vitamin A derivatives, which will act as hormonal cues or intracellularly to regulate essential aspects of adipocyte biology. As agents that prevent adipocyte differentiation hence, expected to decrease fat mass, and inducers of uncoupling protein expression, thus, favoring energy expenditure, retinoids have prompted many investigations to decipher their roles in adipose tissue pathophysiology, which are summarized in this review.

  12. In vitro study on arsenic sulfide (realgar)-induced apoptosis of retinoic acid susceptible or resistant acute promyelocytic leukemia cell lines

    Institute of Scientific and Technical Information of China (English)

    CHEN Si-yu; LIU Shan-xi; LI Xin-min

    2002-01-01

    Objective: To further understand the possible mechanisms of arsenic sulfide (realgar) in the treatment of acute promyelocytic leukemia (APL). Methods: All-trans retinoic acid (ATRA)-susceptible APL cell line (NB4 cells) and ATRA-resistant APL cell line (MR2 subclone) were used as models in vitro. At various times after incubated with various concentrations of realgar, NB4 and MR2 cells were observed by cell viability, cell proliferation and cell morphology; cell cycle and the expression of Annexin V were assayed by flow cytometry. Results: Cell viability and proliferation of NB4 and MR2 cells were inhibited after the treatment,to some extent, in a dose and time dependent manner. 177-711 μg/L of realgar treated NB4 and MR2 cell presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation, apoptosis body could be found by electron microscopy as well. Sub-G1 ceils andcell cycle arrest were observed by flow cytometry. The proportion of Annexin V -FITC+/PI cells, which represent apoptotic cells, was up-regulated. Conclusion: Realgar could induce apoptosis of acute promyelocytic leukemia cell despite its susceptibility to retinoic acid in the way that may be different from retinoic acid.

  13. Retinoid regulated macrophage cholesterol efflux involves the steroidogenic acute regulatory protein.

    Science.gov (United States)

    Manna, Pulak R

    2016-06-01

    Elimination of excess cholesteryl esters from macrophage-derived foam cells is known to be a key process in limiting plaque stability and progression of atherosclerotic lesions. We have recently demonstrated that regulation of retinoid mediated cholesterol efflux is influenced by liver X receptor (LXR) signaling in mouse macrophages (Manna, P.R. et al., 2015, Biochem. Biophys. Res. Commun., 464:312-317). The data presented in this article evaluate the importance of the steroidogenic acute regulatory protein (StAR) in retinoid mediated macrophage cholesterol efflux. Overexpression of StAR in mouse RAW 264.7 macrophages increased the effects of both all-trans retinoic acid (atRA) and 9-cis RA on cholesterol efflux, suggesting StAR enhances the efficacy of retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) ligands. Additional data revealed that atRA enhances (Bu)2cAMP induced StAR and ATP-binding cassette transporter A1 protein levels. Treatment of macrophages transfected with an LXRE reporter plasmid (pLXREx3-Luc) was found to induce the effects of RAR and RXR analogs on LXR activity. PMID:27081671

  14. Induction of differentiation and apoptosis- a possible strategy in the treatment of adult acute myelogenous leukemia.

    Science.gov (United States)

    Bruserud, O; Gjertsen, B T; Huang, Ts

    2000-01-01

    A differentiation block with accumulation of immature myeloid cells characterizes acute myelogenous leukemia (AML). However, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment for the acute promyelocytic leukemia variant of AML. Several agents can induce leukemic cell differentiation for other AML subtypes, although these effects differ between patients. Differentiation may then be associated with induction of apoptosis, and differentiation-inducing therapy may therefore become useful in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. However, it should be emphasized that differentiation and apoptosis can occur as separate events with different regulation in AML cells, and future studies in AML should therefore focus on: A) the identification of new agents with more predictable effects on differentiation and apoptosis; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation/apoptosis induction has a predictable and beneficial effect, and C) further characterization of how AML blast sensitivity to drug-induced apoptosis is modulated by differentiation induction.

  15. Activity Analysis and Preliminary Inducer Screening of the Chicken DAZL Gene Promoter

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2015-03-01

    Full Text Available This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was −383 to −39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA, a retinoic acid receptor alpha agonist (tamibarotene/Am80, or estradiol (E2 could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro.

  16. Activity analysis and preliminary inducer screening of the chicken DAZL gene promoter.

    Science.gov (United States)

    Zhang, Lei; Zhu, Rui; Zuo, Qisheng; Li, Dong; Lian, Chao; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-01-01

    This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was -383 to -39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA), a retinoic acid receptor alpha agonist (tamibarotene/Am80), or estradiol (E2) could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC)-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro. PMID:25807265

  17. [PML-RARα and p21 are key factors for maintaining acute promyelocytic leukemia stem cells survival].

    Science.gov (United States)

    Ding, Fei; Li, Jun-Min

    2011-10-01

    Tumor stem/progenitor cells are the cells with the characteristics of self-renewal, differentiating to all the other cell populations within tumor, which are also regarded as the source of tumor relapse, drug-resistance and metastasis. As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARα to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This review summarizes the latest research results of APL as follows: (1) there probably are two APL stem/progenitor cell populations within APL, and self-renewal and survival of APL stem/progenitor cells highly depend on PML-RARα expression, cell cycle inhibitor p21, self-renewal associated molecules and chemokines; and (2) ATRA and ATO eradicate APL stem/progenitor cells mainly by PML-RARα degradation, FOXO3A activation and the inhibition of self-renewal-associated signaling pathway of sonic hedgehog. These findings are helpful to improve other tumor therapy.

  18. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin.

    Science.gov (United States)

    Charoenputtakun, Ponwanit; Li, S Kevin; Ngawhirunpat, Tanansait

    2015-11-10

    The combined effects of iontophoresis and lipid nanoparticles on drug delivery across human epidermal membrane (HEM) were investigated. The delivery of lipophilic and hydrophilic drugs, all trans-retinoic acid (ATRA), salicylate (SA), and acyclovir (ACV), across HEM from lipid nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), was compared in passive and iontophoresis experiments in vitro. Iontophoresis experiments were also performed with synthetic Nuclepore membrane for comparison. Drug distribution in the skin after iontophoretic delivery with the lipid nanoparticles was examined using a model probe rhodamine B base (RhoB). The drug-loaded lipid nanoparticles had average sizes of ∼ 118-169 nm and a negative zeta potential. Iontophoresis did not enhance the delivery of ATRA across HEM from SLN and NLC. However, HEM distribution study of RhoB suggested that lipophilic drugs could be delivered into the deeper layer of the skin following iontophoretic delivery of the drugs from the lipid nanoparticles. Iontophoresis enhanced the delivery of hydrophilic drug SA with the lipid nanoparticles. Similarly, iontophoresis enhanced the delivery of ACV when it was loaded in SLN. These results suggest that lipid nanoparticles are a promising drug delivery method that can be combined with iontophoresis to improve skin delivery of hydrophilic drugs.

  19. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

    LENUS (Irish Health Repository)

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  20. Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

    Science.gov (United States)

    Quintana, Harry Karmouty; Cannet, Catherine; Zurbruegg, Stefan; Blé, François-Xavier; Fozard, John R; Page, Clive P; Beckmann, Nicolau

    2006-12-01

    Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases. PMID:17029230

  1. Simultaneous measurement of electron temperature and density by a line pair method in the RFP plasma

    Science.gov (United States)

    Watanabe, Masayuki; Shimizu, S.; Ogawa, H.; Shinohara, T.

    2009-11-01

    A line-pair-method has been applied for a simultaneous measurement of the electron temperature and density in ATRAS RFP plasma. Three helium spectrum lines (668nm, 706nm, 728nm) were measured during the discharge at the same time and the electron temperature and density is estimated by using a Collision-Radiation model. To get the signal of the helium impunity line from the RFP discharge, the RFP plasma in the hydrogen gas with a few mixed helium gas was formed. In the typical ATRAS RFP discharge of the plasma current of 60kA, the electron temperature was approximately 50-150 eV and the electron density is the order of 10^18 m-3. During the discharge, the change of the temperature and density are mutually related and this correlation was the almost reverse phase. The periodically change of the temperature and density were also observed. This change synchronizes with a periodically increase of the averaged toroidal magnetic field, which is caused by the toroidal rotation of the increase of the toroidal magnetic field. This rotation, which is deeply related with dynamo effect, makes the plasma energy lose and particles also diffuse toward the plasma edge. As a result, the recycling of the particle and energy are occurred at the same time.

  2. Microbial modification of host long-distance dispersal capacity

    Directory of Open Access Journals (Sweden)

    Hutchings Linda

    2009-06-01

    Full Text Available Abstract Background Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider, Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. Results We show that there is spatial heterogeneity in the prevalence of two maternally acquired endosymbiont infections within the wider E. atra meta-population and we demonstrate through several independent approaches a link between the presence of one of these endosymbionts, Rickettsia, and the tendency for long-distance movement. Conclusion This novel finding that particular endosymbionts can influence host dispersal is of broad importance given the extremely widespread occurrence of similar bacteria within arthropod communities. A bacterial phenotype that limits dispersal has the potential not only to reduce gene flow and thus contribute to degrees of reproductive isolation within species, but also to influence species distribution and thus overall community composition.

  3. Differentiating effect of PPARγ ligand rosiglitazone and all trans-retinoic acid on myeloma cells and its possible mechanism%罗格列酮与全反式维甲酸对骨髓瘤细胞分化的影响及其可能机制

    Institute of Scientific and Technical Information of China (English)

    黄海雯; 陈广华; 常惠荣; Howard C.H.Chow; Anska Y.H.Leung; Raymond Liang; 吴德沛

    2009-01-01

    Objective To investigate the effects of PPARγ ligand(rosiglitazone,RGZ)as well as combined with all trans-retinoic acid(ATRA)on human myeloma cells and try to explore the possible mechanism.Methods Human myeloma cell lines U266 and RPMl.8226 cells were treated with RGZ in the presence or absence of ATRA.Cell proliferation was evaluated by [~3H] thymidine incorporation,cell cycle distribution and CD49e expression were analyzed by flow cytometry,morphology changes were evaluated by Wright-Giemsa staining.and p27~(Klpl)and p21~(Wafl)expression was detected by Western blotting.Results The exposure to RGZ induced proliferation inhibifion in both cell Iines in a dose-dependent manner.After cultured with 5 μmol/L RGZ,the proportion of U266 and RPMl-8226 cells in phase G_0/G_1 was(45.2±6.7)%and(40.3±7.3)%,respectively(P<0.05).The proportion of the cells in phase G_2/M and Swag(52.2±7.4)%and(57.4±9.5)%,respectively(P<0.05).These changes were more evident when the RGZ concentration was increased to 10 μmol/L.A combination of RGZ with ATRA enhanced the growth inhibition and eell cycle arrest effects of RGZ.The RGZ-treated myeloma cells displayed morphological characteristics of cell difierentiation.and more evident signs of differentiation were observed when RGZ wag combined with ATRA.These changes were confirmed by the detection of CD49e expression.The expression of p27~(Klpl)and p21~(Wafl)in myeloma cells was up-regulated by RGZ and this change Was more apparent when RGZ was used in combination with ATRA.Conclusion RGZ Can induce cell cycle arrest and cell differentiation in myeloma cells which maybe caused by up-regulation of p27~(Klpl)and p21~(Wafl)expression.ATRA can enhance these effects of RGZ on multiple myeloma cells and combined nile of thesetwo drugs may show a synergistic effect on myeloma cells.%目的 探讨过氧化物酶体增殖物活化受体γ(PPARγ)的配体罗格列酮(RGZ)与全反式维甲酸(ATRA)对骨髓瘤细胞分化的

  4. Effect of receptor-selective retinoids on growth and differentiation pathways in mouse melanoma cells.

    Science.gov (United States)

    Desai, S H; Boskovic, G; Eastham, L; Dawson, M; Niles, R M

    2000-05-15

    Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor beta (RARbeta) expression, an increase in protein kinase Calpha (PKCalpha) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARalpha and RARgamma and nuclear retinoid X receptors (RXR) alpha and beta constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8, 8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was most effective at inhibiting anchorage-dependent growth, whereas the RARgamma-selective ligand 6-[(5,6,7, 8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)(hydroxyimino)methyl]-2-naphthalen ecarbo xylic acid (SR11254) was most potent at inhibiting anchorage-independent growth. In contrast, 4-(5,6,7,8-tetrahydro-5,5, 8,8-tetramethyl-2-naphthalenecarboxamido)-benzoic acid (Am580), an RARalpha-selective ligand, was the most effective receptor-selective agonist for inducing RARbeta mRNA and increasing the amount of PKCalpha protein. All of the retinoids induced a concentration-dependent increase in AP-1 transcriptional activity, with little difference in effectiveness among the receptor-selective retinoids. A synergistic increase in the amount of PKCalpha was found when an RAR-selective agonist was combined with an RXR-selective agonist. One possible explanation for this result is that an RXR-RAR heterodimer in which both receptors are liganded is required for maximum expression of this critical component of the ATRA-induced differentiation pathway. Our data suggest that synthetic retinoids can activate different growth and

  5. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a. Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3. The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect. The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the micro

  6. HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a novel deacetylase activity-independent function of HDAC3.

    Directory of Open Access Journals (Sweden)

    Pawan Gupta

    Full Text Available TR2 is an orphan nuclear receptor specifically expressed in early embryos (Wei and Hsu, 1994, and a transcription factor for transcriptional regulation of important genes in stem cells including the gate keeper Oct4 (Park et al. 2007. TR2 is known to function as an activator (Wei et al. 2000, or a repressor (Chinpaisal et al., 1998, Gupta et al. 2007. Due to the lack of specific ligands, mechanisms triggering its activator or repressor function have remained puzzling for decades. Recently, we found that all-trans retinoic acid (atRA triggers the activation of extracellular-signal-regulated kinase 2 (ERK2, which phosphorylates TR2 and stimulates its partitioning to promyelocytic leukemia (PML nuclear bodies, thereby converting the activator function of TR2 into repression (Gupta et al. 2008; Park et al. 2007. Recruitment of TR2 to PML is a crucial step in the conversion of TR2 from an activator to a repressor. However, it is unclear how phosphorylated TR2 is recruited to PML, an essential step in converting TR2 from an activator to a repressor. In the present study, we use both in vitro and in vivo systems to address the problem of recruiting TR2 to PML nuclear bodies. First, we identify histone deacetylase 3 (HDAC3 as an effector molecule. HDAC3 is known to interact with TR2 (Franco et al. 2001 and this interaction is enhanced by the atRA-stimulated phosphorylation of TR2 at Thr-210 (Gupta et al. 2008. Secondly, in this study, we also find that the carrier function of HDAC3 is independent of its deacetylase activity. Thirdly, we find another novel activity of atRA that stimulates nuclear enrichment of HDAC3 to form nuclear complex with PML, which is ERK2 independent. This is the first report identifying a deacetylase-independent function for HDAC3, which serves as a specific carrier molecule that targets a specifically phosphorylated protein to PML NBs. This is also the first study delineating how protein recruitment to PML nuclear bodies occurs

  7. Avaliação do Plano Operacional de Comercialização do Turismo: o caso de Bonito, município de Mato Grosso do Sul-Brasil

    Directory of Open Access Journals (Sweden)

    Milton Augusto Pasquotto Mariani

    2011-09-01

    Full Text Available

    O presente estudo tem como objetivo geral analisar as percepções do trade turístico de Bonito acerca do plano de comercialização desenvolvido para o município, buscando a compreensão da interface marketing-turismo. Tratando-se o marketing turístico como uma ferramenta para a conquista e manutenção de clientes, a fim de que a experiência vivenciada pelo turista seja única e inesquecível, o presente estudo justifica-se na busca de contribuições para a gestão pública do destino turístico analisado, com vistas a sua consolidação como pólo na atração de visitantes. Trata-se de um estudo qualitativo, de natureza exploratória, descritiva e explicativa, cujo procedimento de coleta, análise e interpretação dos dados resumiu-se em entrevistas com os atores locais. Os resultados apontam que aproximadamente 89% dos sujeitos consideram o plano importante para o desenvolvimento da atividade turística local, sendo que 44% o consideram importante para “vender” o destino como ícone brasileiro no ecoturismo; 33% o consideram importante por propiciar o direcionamento da região rumo à atração de turistas do mundo todo e 11% o consideram importante como ação estratégica para superar as dificuldades existentes e construir um novo posicionamento estratégico no mercado turístico. Sendo assim, referindo-se ao turismo como um dos principais setores empregatícios e gerador de renda para o município, o plano de comercialização se apresenta como uma ferramenta importante para a consolidação do destino como um verdadeiro pólo na atração de turistas.

  8. Retinoic acid signalling is activated in the postischemic heart and may influence remodelling.

    Directory of Open Access Journals (Sweden)

    Dusan Bilbija

    Full Text Available BACKGROUND: All-trans retinoic acid (atRA, an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors (RARs acting on retinoic acid response elements (RARE. We hypothesized that the retinoic acid (RA signalling pathway is activated in myocardial ischemia and postischemic remodelling. METHODS AND FINDINGS: Myocardial infarction was induced through ligating the left coronary artery in mice. In vivo cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM and cardiofibroblasts (CF were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity in vivo (p<0.001, which was ascribed to the heart through ex vivo imaging (p = 0.002 with the largest signal 1 week postinfarct. This was accompanied by increased cardiac gene and protein expression of the RAR target genes retinol binding protein 1 (p = 0.01 for RNA, p = 0,006 for protein and aldehyde dehydrogenase 1A2 (p = 0.04 for RNA, p = 0,014 for protein, while gene expression of cytochrome P450 26B1 was downregulated (p = 0.007. Concomitantly, retinol accumulated in the infarcted zone (p = 0.02. CM and CF isolated from infarcted hearts had higher luminescence than those from sham operated hearts (p = 0.02 and p = 0.008. AtRA inhibited CF proliferation in vitro (p = 0.02. CONCLUSION: The RA signalling pathway is activated in postischemic hearts and may play a role in regulation of damage and

  9. {alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

    2011-02-15

    We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

  10. Inactivation of Vibrio cholerae O1 El Tor inoculated into Peruvian ''choro'' mussels (Aulacomya ater) and two species of clams (Argopecten purpuratus and Gari solida) using medium-dose irradiation

    International Nuclear Information System (INIS)

    The radiation decimal reduction dose (D10) for Vibrio cholerae O1 biotype El Tor inoculated through the natural feeding system into three species of bivalve mollusks from the Peruvian Pacific coast: ''choro'' mussels (Aulacome ater), ''abanico'' clams (Argopecten purpuratus), and common clams (Gari solida), was determined in vivo. The D10 value obtained in vivo was 0.14 kGy in all mollusks tested. Concurrent studies conducted to determine the potential use of irradiation to extend the microbiological shelf-life of the mollusks during post-irradiation storage at 0-1 deg. C indicated that a dose of 1.0 kGy was optimal for choro mussels and abanico clams, whereas 2.0 kGy produced the best results when treating common clams. Shelf-life extension thus achieved was 31 days for choro mussels, 16 days for abanico clams, and 21 days for common clams. Non-irradiated control samples of all mollusks spoiled after 17 days of refrigerated storage. There were no significant (p<.05) adverse effects from the application of the optimal radiation treatments on the sensory characteristics (i.e. appearance, odor, flavor, and texture) of the mollusks. Total volatile basic nitrogen (VBN) and pH values were examined for use as indexes of seafood freshness. (author)

  11. New approaches for the desing of chiral catalysts. Application in carbonylation reactions.

    OpenAIRE

    Muñoz Moreno, Bianca Karelia

    2007-01-01

    Actualmente, el interés industrial de los productos carbonilados ha atraído la atención de los científicos hacia el desarrollo de nuevos sistemas catalíticos eficientes. La reacción de alcoxicarbonilación de vinil arenos ha sido considerada una ruta alternativa para la obtención de ácidos 2-aril propiónicos, la clase más importante de antiinflamatorios no esteroides. Por otro lado, los copolímeros de monóxido de carbono y olefinas son materiales de gran interés industrial debido a su aplica...

  12. Proceso de transformación del territorio rural del distrito de santa marta

    Directory of Open Access Journals (Sweden)

    Antonio Navarro Hernández

    2014-02-01

    Full Text Available Através del tiempo, el área rural del Distrito de Santa Marta ha sido objeto de sucesivas ocupaciones por grupos poblacionales que atraídos por la oferta natural de sus recursos, procuraronla satisfacción de sus necesidades usufructuando de la misma con sistemas de producción que si hien contribuyeron al desarrollo económicos local, en la mayoría de las veces lesionaron la dinámica ambiental del entorno, dando lugar a alteraciones que se sienten más allá del medio en donde se realiza la explotación de tales recursos.

  13. Una aproximación a la predicción del valor de acciones en la bolsa de valores aplicando técnicas de Data Mining

    OpenAIRE

    Espinosa Muñoz, Javier Isaac

    2015-01-01

    La predicción del valor de las acciones en la bolsa de valores ha sido un tema importante en el campo de inversiones, que por varios años ha atraído tanto a académicos como a inversionistas. Esto supone que la información disponible en el pasado de la compañía que cotiza en bolsa tiene alguna implicación en el futuro del valor de la misma. Este trabajo está enfocado en ayudar a un persona u organismo que decida invertir en la bolsa de valores a través de gestión de compra o venta de acciones ...

  14. 氧化砷对MR2细胞耐药分子表达的影响%The Effect of As2O3 on the Epression of Drug-resistance Molecule in Malignant Neoplasmas

    Institute of Scientific and Technical Information of China (English)

    钱晓萍; 刘宝瑞; 王立峰; 杜娟; 臧秦川

    2003-01-01

    Objective: To detect the action of arsenic trioxide (As2 O3 ) on the expressionof Tumor drug-resistant molecule. Methods: APL cell line MR2 resistant to all-trans retinoic acid (ATRA) was put into research, while APL cell line NB4 was used for control. The immunocytochemical assays were used to detect the expressions of P-glycoprotein ( Pgp ) and Glutathione S-transferase (GST). Results: Not only the expression of Pgp in MR2 cell linw (30%-40%) was significantly higher than that in NB4 cell linc (10%-20%) (p < 0.001), but also the expression of GST in MR2 cell linc (60.4 ± 4.0)- (66.5 ± 4.4) was significantly higher than that in NB4 cell linc (28.3 ± 5.6)- (31.2 ± 5.1) ( P < 0.05). As2 O3 at the concentration of 0.5-2.0μmol/l could significantly aecrease the expression of Pgp and GSTπ, but could do nothing about the expression of GSTα and GSTμ . Conclusion: The lower expression of Pgp and GSTπ might be the sensitive indications of frustrating drug-resistance, while GSTα and GSTμ might not be the case. ATRA might be the substrates of Pgp transmission and GSTπ catalysis.%目的:探讨三氧化二砷(As2O2)对肿瘤耐药分子的作用.方法:以耐全反式维甲酸(ATRA)早幼粒白血病细胞株MR2为研究对象,以非耐药急性早幼粒白血病细胞株NB4为对照组,用免疫组化法观察P-糖蛋白(Pgp)、谷胱甘肽S转移酶(GST)的表达.结果:MR2细胞PgP表达(30%~40%)较NB4细胞(10%~20%)明显增强(P<0.001),MR2细胞GSTπ表达(60.4±4.0)~(66.5±4.4)较NB4细胞(28.3±5.6)~(31.2±5.1)明显增强(P<0.05).0.5~2.0 μmol/L As2O3能显著降低MR2细胞Pgp、GSTπ表达,而对GSTα、GSTμ无影响.结论:Pgp、GSTπ表达的下调,可能是As2O3克服耐药的敏感性指标,而GSTα、GSTμ则否.全反式维甲酸(ATRA)可能是Pgp转运底物和GSTπ催化作用底物.

  15. Selección de conexiones de acero para zonas sísmicas con base en criterios de confiabilidad

    Directory of Open Access Journals (Sweden)

    David de León Escobedo

    2011-01-01

    Full Text Available Los hallazgos encontrados a raíz del terremoto de Northridge en 1994 han atraído actualmente la atención de los especialistas, sobre todo en cuanto a los problemas de diseño y seguridad de las conexiones soldadas para estructuras ubicadas en zonas sísmicas. Para equilibrar la seguridad requerida deben tomarse decisiones en relación con los costos para prevenir la posibilidad de excederse algún estado límite de servicio. Las técnicas de confiabilidad estructural proporcionan el marco adecuado para incluir las incertidumbres inherentes en el proceso de diseño. La formulación propuesta permite apoyar a diseñadores y a constructores para la selección del tipo de conexión más conveniente para las zonas sísmicas.

  16. 雄黄治疗维甲酸耐药急性早幼粒细胞白血病临床研究

    Institute of Scientific and Technical Information of China (English)

    关键平; 袁炜; 杨浩; 宋春利; 王梦昌

    2002-01-01

    目的观察诱导凋亡剂雄黄对耐维甲酸(ATRA)的急性早幼粒细胞白血病(APL)的治疗效果及毒副作用.方法对比应用雄黄治疗APL2 0例前后结果.结果完全缓解(CR)17例,部分缓解(PR)1例,总有效率(CR +PR)90%.结论雄黄对ATRA耐药的APL仍有较高的缓解率,二者无交叉耐药,毒性小,适用于临床推广应用.

  17. Nepotismo e poder na Arquidiocese de Braga (1245-1374)

    OpenAIRE

    Costa, Maria Antonieta Moreira da

    2005-01-01

    O estudo do nepotismo no seio da Igreja Católica da Idade Média tem atraído alguns investigadores alemães, ingleses e italianos, mas no caso português são poucos os autores que mencionam esta prática, dedicando-lhe apenas vagas referências em obras de carácter geral. Actualmente, o conhecimento do uso deste costume pode trazer à luz do dia uma outra realidade para além da tradicional história política e institucional do Estado Pontifício. Pode revelar-nos outros canais de exercício do poder e...

  18. Materiales nanoestructurados céramicos como vehículo para la liberación de principios activos

    OpenAIRE

    Marlene Lariza Andrade Guel; Lourdes Díaz Jiménez; Dora Cortés Hernández

    2013-01-01

    Los materiales nanoestructurados han atraído especial atención debido a sus propiedades químicas y físicas que permiten nuevas aplicaciones en campos de la medicina y farmacología como vehículos para la liberación de principios activos que ayudan a transportarlos al sitio de interés controlando la dosificación. Algunos materiales nanoestructurados como dióxido de titanio TiO2, dióxido de zirconio ZrO2, dióxido de silicio SiO2 o hidróxidos dobles laminares, destacan por sus propiedades y aplic...

  19. Promoción de la lectura

    OpenAIRE

    Valdéz, Julia

    2006-01-01

    Al hablar de "promoción de la lectura", por lo general se piensa en niños o, a lo sumo, en adolescentes, en el ámbito escolar casi exclusivamente y en lectura de ficciones. Considero necesario repensar estos supuestos. Quizás centrándonos en tres preguntas se pueda ver la situación desde otros ángulos: ¿la promoción de la lectura es sólo para una determinada edad? ¿qué se entiende por "lectura"? ¿quién o quiénes son los responsables de esta tarea? Es cierto que la edad más propicia para "atra...

  20. Atividade e moléculas antioxidantes de cogumelos silvestres comestíveis do género Agaricus

    OpenAIRE

    Martins, Anabela; Pereira, Eliana; Barros, Lillian; Isabel C. F. R. Ferreira

    2012-01-01

    Os cogumelos contêm vários compostos antioxidantes nomeadamente, compostos fenólicos (e.g. ácidos fenólicos), tocoferóis e carotenóides. Entre as substâncias biologicamente ativas presentes nos cogumelos, os compostos fenólicos têm atraído muita atenção devido às suas excelentes propriedades como antioxidantes e ao seu potencial anti-inflamatório ou antitumoral [1,2]. Neste trabalho, foi avaliado o potencial antioxidante de seis espécies silvestres comestíveis do género Agaricus: Agaricus bis...

  1. Contrarios y aprendizaje : preferencia por las diferencias salientes entre objetos

    OpenAIRE

    Llach Carles, Sílvia; Ribot i Mundet, Maria Dolors de

    2010-01-01

    A partir de la hipótesis de que los contrarios son un elemento adecuado para las tareas de aprendizaje, en este estudio se ha investigado la respuesta de niños y adultos ante una serie de estímulos que se han agrupado en más opuestos y menos opuestos. La finalidad de este trabajo es investigar si los sujetos analizados se sienten más atraídos por los objetos que muestran una relación de oposición mayor que los que no la muestran. Los resultados evidencian que los niños escogen más los contrar...

  2. Application of transfer function model to predict transport of Atrazine in soil%应用传递函数模型预报农药阿特拉津在土壤中的运移

    Institute of Scientific and Technical Information of China (English)

    任理; 毛萌

    2002-01-01

    本文首先对农药阿特拉津(Atrazine)在稳定流场饱和均质土壤中的运移进行了室内实验研究,采用易混合置换的方法,获得了示踪溶质Br-和Atrazine同步脉冲输入1h后的出流浓度动态;其次由批技术得到Atrazine的分配系数,进而获得阻滞因子,在此基础上应用传递函数模型,根据示踪溶质的迁移预报了吸附作用存在时Atrazine在土壤中的运移动态.

  3. Oncogenic fusion proteins expressed in immature hematopoietic cells fail to recapitulate the transcriptional changes observed in human AML

    DEFF Research Database (Denmark)

    Rapin, N; Porse, B T

    2014-01-01

    Reciprocal chromosomal translocations are observed in one-third of acute myeloid leukemia (AML) cases. Targeting and understanding the effects of the resulting aberrant oncogenic fusion proteins may help developing drugs against specific leukemic subtypes, as demonstrated earlier by the use of ATRA...... in acute promyelocytic leukemia. Hematopoietic stem/progenitor (HSPCs) cells transduced with oncogenic fusion genes are regarded as promising in vitromodels of their corresponding AML subtypes. Here, we critically assessed the potential of such in vitro models using an integrative bioinformatics approach....... Surprisingly, we found that the gene-expression profiles of CD34+ human HSPCs transformed with the potent oncogenic fusion proteins AML-ETO or MLL-AF9, only weakly resembled those derived from primary AML samples. Hence, our work raises concerns as to the relevance of the use of in vitro transduced cells...

  4. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

    Directory of Open Access Journals (Sweden)

    Harsh Shah

    2015-01-01

    Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  5. Los problemas del aprendizaje en la escuela. Perspectiva social

    Directory of Open Access Journals (Sweden)

    Sindo FROUFE QUINTAS

    2009-11-01

    Full Text Available Pocos temas han tenido tanta importancia y repercusión en la escuela como el problema de los trastornos de aprendizaje desde una perspectiva social/sociológica. Distintos tipos de profesionales como psicólogos, neurólogos, ópticos, fisioterapeutas, pedíatras, pedagogos y maestros han manifestado/mostrado un gran interés por conocer/descifrar en profundidad su etiología. Quedan aún muchas lagunas/misterios por aclarar. La mente humana es duramente compleja. La cultura es un bien que todo el mundo desea conquistar. Por ella se entra en el mundo de la civilización tecnológica y en la interpretación correcta de los distintos sistemas de comunicación que abren nuevos horizontes al hombre de la técnica.

  6. Adaptación para multiples GPU de un simulador de actividad eléctrica en el corazón

    OpenAIRE

    García Mollá, Víctor Manuel; Vidal Maciá, Antonio Manuel; Liberos Mascarell, Alejandro; Climent, Andreu M.

    2013-01-01

    La simulación de la actividad eléctrica del corazón se calcula mediante la resolución de un gran sistema de ecuaciones diferenciales ordinarias, que necesita una enorme cantidad de tiempo de computación. Sin embargo, en los últimos años se están introduciendo, en el ámbito de la computación de alto rendimiento, las unidades de procesamiento gráfico (GPU). Estos potentes dispositivos han atraído a grupos de investigación que requieren simular la actividad eléctrica del corazón. El grupo de inv...

  7. Mosquitoes of the mangrove forests of India: part six--Kundapur, Karnataka and Kannur, Kerala.

    Science.gov (United States)

    Rajavel, A R; Natarajan, R; Vaidyanathan, K

    2006-12-01

    Mosquitoes of 26 species belonging to 16 subgenera and 11 genera were recorded in the Kundapur mangroves of Karnataka, and 17 species belonging to 11 subgenera and 7 genera were recorded in the mangroves of Kannur, Kerala along the west coast of India. Genera recorded were Aedes, Anopheles, Armigeres, Culex, Heizmannia, Lutzia, Mansonia, Ochlerotatus, Tripteroides, Uranotaenia, and Verrallina. Species common to both mangrove forests were Ae. albopictus, Ae. vittatus, An. jamesi, Ar. subalbatus, Cx. gelidus, Cx. infantulus, Cx. pseudovishnui, Cx. sitiens, Cx. tritaeniorhynchus, Oc. wardi, Ur. atra, and Ve. luguhris. Tree holes and swamp pools were the common larval habitats, with more species occurring in tree holes in Kundapur than in Kannur. Adults of Ae. albopictus, Ae. vittatus, Ar. aureolineatus, Ar. subalbatus, Cx. bitaeniorhynchus, Cx. sitiens, Ma. uniformis, and Ve. lugubris bloodfed on humans. PMID:17304922

  8. Malária e aspectos hematológicos em moradores da área de influência dos futuros reservatórios das hidrelétricas de Santo Antônio e Jirau, Rondônia, Brasil Malaria and hematological aspects among residents to be impacted by reservoirs for the Santo Antônio and Jirau Hydroelectric Power Stations, Rondônia State, Brazil

    OpenAIRE

    Tony Hiroshi Katsuragawa; Roberto Penna de Almeida Cunha; Daniele Cristina Apoluceno de Souza; Luiz Herman Soares Gil; Rafael Bastos Cruz; Alexandre de Almeida e Silva; Mauro Shugiro Tada; Luiz Hildebrando Pereira da Silva

    2009-01-01

    Em Rondônia, prevê-se a construção de mais duas usinas hidrelétricas (UHE) no rio Madeira, a montante da cidade de Porto Velho, Rondônia, Brasil (de Santo Antônio e Jirau). O objetivo deste trabalho foi analisar a prevalência da malária antes do início da implantação das obras civis e fazer considerações sobre os impactos da doença com o ingresso de milhares de trabalhadores e agregados atraídos pelas oportunidades de emprego e comércio. Os resultados obtidos mostram que a malária se faz pres...

  9. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  10. The association of environmental changes and the replacement of mosquito fauna in the Colombo District, Sri Lanka

    Directory of Open Access Journals (Sweden)

    BAS Priyangika

    2014-06-01

    Full Text Available The mosquito survey was carried out for 8 months between October 2009 and May 2010. Investigations included 12 randomly selected urban (6 and semi-urban (6 areas in the Colombo District of Sri Lanka. Thirty eight mosquito species were found and Anopheles interruptus, An. pseudojamesii, Aedes stenovensoni, Ae. edwardsi, Ae. vittatus, Culex  barraudi, Cx. fatigans, Cx. univittatus, Cx. aculeatus, Cx. purplexus, Cx. spiculosus, Cx. quadripalpis, Cx. halifaxi, Uranotaenia atra, Ur. unguiculata were new findings that were not recorded  previously in the period 1981-1982 from the same locations although 11 different breeding habitats were examined. Rainfall had a direct relation (P=0.000 with the distribution and the density of mosquitoes. Unplanned urbanization, human activities and irregular or non-disposal of domestic waste products have led to a population replacement of the mosquito fauna in these locations.

  11. Therapeutic strategies targeting cancer stem cells.

    Science.gov (United States)

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-04-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  12. Acute Promyelocytic Leukemia in Four Year Old Female Child - A Case Report

    Directory of Open Access Journals (Sweden)

    Anirudha V. Kushtagi

    2014-07-01

    Full Text Available Leukemia is the most common malignancy of childhood representing about 30 % of oncohematological diseases diagnosed in children less than 15 years of age. We report the case of a 4 year old girl with acute promyelocytic leukemia whose blasts showed the morphology characteristic of acute promyelocytic leukemia variant. The case is reported because in the paediatric population the acute promyelocytic leukemia is a rare occurrence moreover, it represent a true oncohematology emergency, in this case the laboratory has a significant role since the timing of diagnosis must be very short. It helps in therapeutic protocols compared to conventional therapeutic protocols in Acute Myeloid Leukemia (AML, the introduction of retinoid All-Trans-Retinoic Acid (ATRA, both in children and adults with Acute Promyelocytic Leukemia (APL, has significantly reduced the early mortality.

  13. Estudio de diseño y plan de marketing de un nuevo verdejo frizzante de bodegas Rodriguez Sanzo

    OpenAIRE

    Calvo Gómez, Diego

    2015-01-01

    Dada la difícil situación del mercado de vino en España, donde cada vez se consume menos vino, sobre todo la gente joven, que no se siente atraída por él y beben otras bebidas alcohólicas como la cerveza principalmente; se busca un nuevo producto que les sea más atractivo. Se decidió elaborar un vino verdejo frizzante, por lo de moda que se está poniendo este tipo de productos y así conseguir llegar a un nicho de población que no suele ser consumidor habitual de vinos tranquilos convencion...

  14. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia

    OpenAIRE

    Rafael Henriques Jácomo; Lorena Lobo de Figueiredo-Pontes; Eduardo Magalhães Rego

    2008-01-01

    A leucemia promielocítica aguda (LPA) é um modelo da aplicabilidade clínica dos conhecimentos moleculares fisiopatológicos. Caracteriza-se por alterações genéticas recorrentes que envolvem o gene do receptor alfa do ácido retinóico. A conseqüência é uma proteína com sensibilidade reduzida ao ligante, com bloqueio da diferenciação mielóide. Entretanto, doses suprafisiológicas do ácido all-trans-retinóico (ATRA) são capazes de suplantar esta deficiência, e este é o princípio fundamental do trat...

  15. Lichensphere: a protected natural microhabitat of the non-lichenised fungal communities living in extreme environments of Antarctica.

    Science.gov (United States)

    Santiago, Iara F; Soares, Marco Aurélio; Rosa, Carlos A; Rosa, Luiz H

    2015-11-01

    We surveyed the diversity, distribution and ecology of non-lichenised fungal communities associated with the Antarctic lichens Usnea antarctica and Usnea aurantiaco-atra across Antarctica. The phylogenetic study of the 438 fungi isolates identified 74 taxa from 21 genera of Ascomycota, Basidiomycota and Zygomycota. The most abundant taxa were Pseudogymnoascus sp., Thelebolus sp., Antarctomyces psychrotrophicus and Cryptococcus victoriae, which are considered endemic and/or highly adapted to Antarctica. Thirty-five fungi may represent new and/or endemic species. The fungal communities displayed high diversity, richness and dominance indices; however, the similarity among the communities was variable. After discovering rich and diverse fungal communities composed of symbionts, decomposers, parasites and endemic and cold-adapted cosmopolitan taxa, we introduced the term "lichensphere". We hypothesised that the lichensphere may represent a protected natural microhabitat with favourable conditions able to help non-lichenised fungi and other Antarctic life forms survive and disperse in the extreme environments of Antarctica.

  16. Prevenção primária de doenças cardiovasculares na obesidade infantojuvenil: efeito anti-inflamatório do exercício físico Early prevention of cardiovascular diseases in juvenile obesity: the anti-inflammatory effect of physical exercise

    OpenAIRE

    Márcia Braz Rossetti; Raquel Rodrigues Britto; Rocksane de Carvalho Norton

    2009-01-01

    A pandemia da obesidade juvenil e do sedentarismo está relacionada com o maior risco de doenças cardiovasculares no futuro. Ambas com fisiopatologia inflamatória, essas condições têm atraído significativa atenção científica. O início dos eventos que agridem o endotélio vascular pode ocorrer na infância, porém, sinais clínicos da aterosclerose geralmente só aparecem na fase adulta. O tecido adiposo é hoje reconhecido por seu papel ativo, induzindo a produção de citocinas pró e anti-inflamatóri...

  17. Memoria y relato

    Directory of Open Access Journals (Sweden)

    Igoa, José Manuel

    2004-01-01

    Full Text Available En este artículo se hacen algunas reflexiones acerca de las relaciones entre la memoria y el relato partiendo de un intento de aclarar la semántica de estos dos términos, sobre todo del primero. En su primera parte, se examinan diversas maneras de entender y abordar estas relaciones desde una óptica predominantemente psicológica. La segunda parte del artículo se dedica a explorar el papel que desempeñan los diversos sistemas y mecanismos de la memoria humana, tal y como se conciben y estudian actualmente en la Psicología Cognitiva, en las tareas de comprender y recordar relatos. También se subrayan en ella algunos problemas relevantes que han atraído la atención de los investigadores y expertos en la materia.…

  18. Estudio de algunos géneros bacterianos asociados a la rizosfera de los cultivos de gerbera (Gerbera jamesonii y clavel (Dianthus barbatus, Dianthus caryophyllus

    Directory of Open Access Journals (Sweden)

    Annia Hernández

    2000-01-01

    Full Text Available En este trabajo se realizó la caracterización de algunos géneros bacterianos presentes en la rizosfera de los cultivos de gerbera (Gerbera jamesonii y clavel (Dianthus barbatus y Dianthus caryophyllus, en un suelo Ferralítico Rojo compactado de San José de las Lajas. También se estudió la quimioatracción de los exudados radicales de estos cultivos hacia diferentes rizobacterias (Pseudomonas (Burkholderia cepacia, P. fluorescens y Azospirillum brasilense. En ambos casos se utilizó el Modelo Espermosférico. Los resultados obtenidos demostraron que Pseudomonas constituye una población dominante en relación con Azospirillum, Bacillus y Streptomyces. Pseudomonas (Burkholderia cepacia fue la cepa más fuertemente atraída por los exudados radicales de gerbera y clavel, a los 14 días y 40 minutos de exposición

  19. El desarrollo de habilidades lingüísticas en el marco de la alfabetización digital : una investigación con la lectura de "La isla del Tesoro"

    OpenAIRE

    Garre Marín, Raúl

    2015-01-01

    Con esta tesis doctoral se pretende incidir en la relación que el uso de las tecnologías de la información y de la comunicación y de formatos por los que los jóvenes se sienten atraídos (videojuegos, cine, cómics) tiene con el desarrollo de las habilidades lingüísticas del alumnado, frente al uso de formatos analógicos tradicionales. Se sostiene la idea de que, ante las nuevas formas de lectura y escritura impuestas en la sociedad por el masificado uso de las tecnologías de la información y d...

  20. DESIGN EM SITES DE ENCONTRO: PROMESSAS DE AMOR VERDADEIRO, RÁPIDO, ANÔNIMO E GRATUITO

    Directory of Open Access Journals (Sweden)

    Ana Beatriz Pereira de Andrade

    2011-10-01

    Full Text Available O presente ensaio parte de pesquisa em desenvolvimento sobre a atração amorosa na Internet. Os sites de namoro são considerados lugar de encontro na rede, oferecendo aos seus usuários inúmeros recursos interativos para facilitar o conhecimento de possíveis parceiros amorosos. O design das páginas principais e anúncios são fonte de rico material de análise, reforçando mensagens atrativas que podem contribuir para o sucesso destes sites junto à sua clientela. Pretende-se apontar aspectos relacionados às estratégias utilizadas pelos sites para atrair pessoas.

  1. Cryptic PML-RARα positive acute promyelocytic leukemia with unusual morphology and cytogenetics

    Directory of Open Access Journals (Sweden)

    Goyal Manu

    2010-10-01

    Full Text Available Acute Promyelocytic Leukemia (APL is different from other forms of acute myeloid leukemia (AML, to the reason being the potential devastating coagulopathy and the sensitivity to all-trans retinoic acid (ATRA and arsenic trioxide (As 2 O 3 . We hereby present a case of APL, morphologically distinct from the hypergranular APL; however, the flow cytometry revealed a characteristic phenotype showing dim CD45, bright CD13, bright CD33 and dim CD117 positivity. These were negative for CD34, HLA-DR, B-lymphoid and T-lymphoid lineage markers. Conventional cytogenetics revealed a distinct karyotype of a male with translocation t(4;15(q34.2:q26.3. However, interphase florescence-in-situ hybridization (FISH revealed PML/RARA fusion signal on chromosome 15 in 90% cells. The cryptic translocations may be missed on conventional cytogenetics, however, need to be picked by other techniques as FISH.

  2. Immunomodulatory effects of honey cannot be distinguished from endotoxin

    DEFF Research Database (Denmark)

    Timm, Michael; Bartelt, Stine; Hansen, Erik Wind

    2008-01-01

    In recent years, the use of honey has re-emerged as a remedy for wound treatment. Effects of honey have been related to the presence of an unidentified component that induces release of inflammatory cytokines from monocytic cells. The present study was intended to further characterize the reported...... in vitro effects of honey. Our results show that natural honeys induce interleukin-6 release from Mono Mac 6 cells as well as release of reactive oxygen species from all-trans retinoic acid (ATRA) differentiated HL-60 cells. The natural honeys contained substantial amounts of endotoxin, and the responses...... observed in the cell based assays were similar to the responses induced by endotoxin alone. In addition, we determined that the immunomodulatory component present in the natural honeys was retained in the ultra filtrated fraction with a molecular weight greater than 20 kDa. The component was resistant...

  3. Mutual exclusivity analysis of genetic and epigenetic drivers in melanoma identifies a link between p14ARF and retinoic acid receptor β signaling

    DEFF Research Database (Denmark)

    Dahl, Christina; Christensen, Claus; Jonsson, Goran;

    2013-01-01

    patterns. We found statistically significant mutual exclusivity among components of each of the p16INK4A-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT pathways. In addition, we found an inverse correlation between promoter hypermethylation of RARB (encoding retinoic acid receptor β (RARβ)) and CDKN2A alterations...... affecting p14ARF (P < 0.0001), suggesting a functional link between RARβ signaling and the melanoma-suppressive activities of p14ARF. We show that all-trans retinoic acid (ATRA) can increase the expression of p14ARF in primary human melanocytes, and that the steady-state levels of p14ARF in these cells are...

  4. El mundo de la prensa rosa: análisis del discurso escrito en la revista ¡Hola!

    OpenAIRE

    Roy-Orenes, Chloé

    2012-01-01

    Hoy en día, vivimos en una sociedad cada vez más atraída por los medios de comunicación como la televisión, el cine, la radio y la prensa, lo que los especialistas denominan mass media o medios de comunicación de masas. Básicamente, diremos que unos emisores mínimos transmiten mensajes a una mayoría de receptores, la denominada sociedad de masas. En España, en los inicios de los años 40 del siglo xx, nació el género periodístico denominado prensa rosa, entendiendo por este nombre la que se de...

  5. What's behind the word? Assay for nonconformity

    Directory of Open Access Journals (Sweden)

    Jaime Torres

    2008-06-01

    Full Text Available El valor, sentido, uso y significado que tiene la palabra pueden ser ubicados en un escenario multidireccional: en el plano de lo real o en el plano de lo simbólico; en el uso práctico o en la imaginación; en el hacer y en el desear. La palabra nos ha conducido en la historia por el misticismo (la magia, por la verdad de las cosas (la ciencia, por ello es que nos provoca inquietud y nos atrae; toda palabra genera sospecha, sorprende, domina, ilusiona, entristece y libera; sin ella no podemos existir en el mundo, ni tampoco dar cuenta que caminamos en él, y sin su presencia no podríamos transformarlo.

  6. Marca e Imagem de um País: Considerações sobre a Copa do Mundo de 2014 e a Promoção do Brasil.

    OpenAIRE

    Marco Antonio Ocke

    2013-01-01

    O marketing de lugares com foco na promoção da imagem de cidades, estados e países enfoca a utilização das atividades de marketing como forma de contribuir com o desenvolvimento socioeconômico da região captando recursos e investimentos através da construção de uma imagem forte e a conseqüente atração de seus públicos de interesse. Como metodologia, o artigo parte de uma revisão da literatura da gestão de imagem e marca-país, passando pelo estudo de casos das Copas do Mundo de Futebol da FIFA...

  7. Extramedullary relapse in lumbar spine of patient with acute promyelocytic leukemia after remission for 16 years: a case report and literature review.

    Science.gov (United States)

    He, Zhengmei; Tao, Shandong; Deng, Yuan; Chen, Yue; Song, Lixiao; Ding, Banghe; Chen, Kankan; Yu, Liang; Wang, Chunling

    2015-01-01

    Acute promyelocytic leukemia (APL) is a common myeloid leukemia. At the newly diagnosed stage, it can be fatal because of the serious complication-disseminated intravascular coagulation. With the advent and early application of all-trans retinoic acid, most APL patients can achieve a long-term survival, and only a minority of patients will develop extramedullary relapse after remission. The most common site of extramedullary relapse is central nervous system, while other sites are relatively rare. Here, we report a particularly rare APL patient who experienced extramedullary relapse with lumbar spine as the isolated site after a rather long time of remission for 16 years. At the time of relapse, the main clinical manifestations of the patient are obvious low back pain, weakness in lower limbs and limitation of activity. After treatment of local radiotherapy combined with ATRA and arsenic trioxide, the patient achieved and maintained a second complete remission by now. PMID:26885224

  8. Morphological and acoustic characters of Cicadatra platyptera Fieber, 1876

    Directory of Open Access Journals (Sweden)

    Abbas Mol

    2013-04-01

    Full Text Available Acoustic and morphological characters are very important to distinguish species of Cicadidae. In this study, the morphological and acoustic characters of Cicadatra platyptera Fieber, 1876 (Hemiptera, Cicadidae collected from Turkey were analysed. The external morphological structures of two species were drawn and photographs of some specimens were taken. We evaluated taxonomically important morphological characters such as body shape, colors, patterns, structure, and genital structure. We evaluated measurements of external morphological structures and acoustics characters of C. platyptera from Turkey, partly with statistical analyses. Morphological characters were compared and differentiated from the closely related species, C. atra. The distribution in Turkey including previous records and the material examined were shown on a map, and the distribution in Palearctic Region was given.

  9. Reacciones de formación de enlaces C-C catalizadas por metales de transición y factores que les afectan

    OpenAIRE

    Noverges Pedro, Bárbara

    2015-01-01

    La síntesis y funcionalización de compuestos carbonílicos ha atraído la atención de los químicos a lo largo del tiempo ya que el grupo carbonilo es una función muy versátil en química orgánica y está presente en numerosos compuestos con actividad biológica. Por su parte, las reacciones de acoplamiento cruzado de dos y tres componentes son metodologías que actualmente se aplican a nivel tanto académico como industrial debido a que requieren condiciones suaves de reacción, la extracción de los ...

  10. La Universidad como espacio de mediación cultural

    Directory of Open Access Journals (Sweden)

    Willem FRIJHOFF

    2010-03-01

    Full Text Available RESUMEN: Los organizadores de este congreso me han concedido el tremendo honor de situar mi conferencia al final de nuestros trabajos, incluso recortando el tiempo disponible hasta un punto extremo. Me atrae la tentación de entregar un breve resumen de lo que se ha dicho y tratado, y ello porque algunas de las contribuciones que aquí se han presentado cosquillean, incluso provocan hasta un grado difícil de aguantar la conciencia profesional del historiador que soy. No se me ha pedido preparar una síntesis o una réplica. Por eso no lo haré. Al menos en la forma debida, porque tampoco puedo escabullirme del todo. ¿No es acaso la historia, como decía mi compatriota, el eminente historiador de la cultura que era Johan Huizinga, «una perpétua discusión»?

  11. Mechanism of retinoid receptors in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375

    Institute of Scientific and Technical Information of China (English)

    NIU Xin-wu; PENG Zhen-hui; FENG Jie; MA Hui-qun; LIU Chao; YUAN Jing-yi

    2005-01-01

    @@ Malignant melanoma is a common cancer of skin. Its incidence is growing rapidly in recent years,1 however, there is no effective therapy for this cancer. Retinoids are metabolites or derivatives of vitamin A. They are essential for growth, differentiation, and maintenance of epithelial tissues.2 Previous studies showed that retinoids could inhibit growth of many kinds of malignant tumor cell lines and induce its apoptosis,3,4 including malignant melanoma cell lines.5 Some retinoids have therapeutic action to malignant melanoma, such as all-trans retinoic acid (ATRA) and 13-cis-RA.6,7 Retinoids take effects mainly through two kinds of nuclear receptors, retinoic acid receptor (RAR) and retinoic acid X receptor (RXR). In this study, we have investigated the effects of diverse retinoids and receptor agonists in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375.

  12. Dissolução e reativação de relacionamentos cliente-empresa: estudo exploratório

    OpenAIRE

    Lopes, Luísa; Brito, Carlos Henrique; Alves, Helena

    2012-01-01

    Os mercados apresentam hoje em dia elevados níveis de competição que, com frequência, dão origem a menores índices de lealdade por parte dos clientes. Isto significa que o sucesso empresarial depende não só da atração e retenção de clientes, mas também da prevenção e gestão do abandono (churn) e da recuperação de clientes perdidos (win-back). Este estudo tem por objetivo explorar a dinâmica dos relacionamentos com o cliente na fase pós-dissolução. Com base numa revisão de literatura, em conte...

  13. Utilization of the human cell line HL-60 for chemiluminescence based detection of microorganisms and related substances

    DEFF Research Database (Denmark)

    Timm, Michael; Hansen, Erik W; Moesby, Lise;

    2006-01-01

    In this paper we describe a new pyrogen assay using the human leukemia cell line HL-60. The cell line is differentiated using all-trans retinoic acid (ATRA) to generate a cell population that resembles mature granulocytes. The differentiated HL-60 cell is capable of generating reactive oxygen...... species (ROS) when challenged with pyrogenic substances. In a luminol enhanced chemilumimetric assay the responsiveness of differentiated HL-60 cells is tested towards Salmonella typhimurium, Bacillus subtilis, Saccharomyces cerevisiae, Candida albicans, lipopolysaccharide (LPS) and lipoteichoic acid (LTA......). The results show a poor sensitivity to S. typhimurium but displays good sensitivity towards B. subtilis, LTA and LPS. Furthermore, the sensitivity towards the yeasts C. albicans and S. cerevisiae is considerably better than obtained in other in vitro cell systems. Overall these results indicate that the HL-60...

  14. HOXB6-mRNA and its gene expression in the differentiation process of human cytomegalovirus-infected hematopoietic stem progenitor cells into granulocyte and erythrocyte progenitor cells%经人巨细胞病毒感染人脐血造血干细胞向粒-巨噬系和红系祖细胞增殖过程中HOXB6-mRNA及其基因表达

    Institute of Scientific and Technical Information of China (English)

    刘文君; 陈艾; 陈红英; 冉伶; 郭渠莲

    2008-01-01

    BACKGROUND: Is the inhibition of the hematopoietic stem progenitor cell (HSPC) proliferation and differentiation after human cytomegalovirus (HCMV) infection associated with abnormal expression of infected cell proliferated gene?OBJECTIVE: To observe the HOXB6-mRNA expression in the process of proliferation and differentiation of HCMV-infected HSPC into colony-forming unit granulocyte-macrophage (CFU-GM) and colony-forming unit erythroid (CFU-E).DESIGN: A controlled observation.SETTING: Laboratory for Molecular Biology, Affiliated Hospital of Luzhou Medical College, Lanzhou, Gansu Province, China.MATERIALS: All cord blood (CB) specimens were provided by the Obstetrics Department of Affiliated Hospital of Luzhon Medical College. They were collected from the umbilical vein of normal term neonates delivered spontaneously. All neonate mothers were healthy and HBS-Ag-negative. HCMV-IgM antibody revealed by routine ELUSA and HCMV-DNA checked by PCR were undetectable. Written informed consent for the laboratory measurements was obtained from each neonate mother, and the protocol was approved by the hospital's Ethics Committee. HCMV-AD169 strains were obtained from the Institute of Virology, Chinese Academy of Preventive Medicine. All-trans retinoic acid (ATRA, lot No. 20010126) was provided by Chongqing Huapont Pharm. Co., Ltd., China.METHODS: This study was performed at the Laboratory of Molecular Biology (state-level), Affiliated Hospital of Luzhou Medical College of Luzhou Medical College from April 2006 to April 2007. Cord blood mononuclear cells were separated for HSPC culture. According to different interventions, the study consisted of 4 groups. Control group: no HCMV virus solution was added and equal volume of culture medium was added instead. HCMV group: 105 PFU/mL HCMV-AD169 virus solution was added to the culture system. ATRA group: ATRA was added into the cultivation system at the final concentration of 60 μ mol/L. HCMV+ATRA group: ATRA was added into the

  15. Retinoid-like activity and teratogenic effects of cyanobacterial exudates.

    Science.gov (United States)

    Jonas, Adam; Buranova, Veronika; Scholz, Stefan; Fetter, Eva; Novakova, Katerina; Kohoutek, Jiri; Hilscherova, Klara

    2014-10-01

    Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be

  16. Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Nami Nishikiori

    2008-03-01

    Full Text Available Nami Nishikiori1,2, Makoto Osanai2, Hideki Chiba2, Takashi Kojima2, Shuichiro Inatomi1,2, Hiroshi Ohguro1, Norimasa Sawada2Departments of 1Ophthalmology and 2Pathology, Sapporo Medical University School of MedicinePurpose: This study was conducted to investigate whether retinoic acids (RAs had any effect on apoptosis during the development of diabetic retinopathy.Methods: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA (seven mice and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarboxamido] benzoic acid (Am580 (nine mice. The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay.Results: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean value and SD: 37.8 ± 6.9, whereas when diabetic mice were treated with RAs, the number of apoptotic cells significantly decreased (mean value and SD: 9.9 ± 6.4 for the seven ATRA-treated diabetic mice and 9.8 ± 5.9 for the nine Am580-treated diabetic mice (p < 0.05.Conclusion: Treatment with RAs decreases apoptosis during the development of diabetic retinopathy.Keywords: retinoic acids, apoptosis, diabetic retinopathy, glial cell line-derived neurotrophic factor

  17. Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPa p42 versus p30 may contribute in part, to aberrant C/EBPa activity in acute leukemias

    Directory of Open Access Journals (Sweden)

    William Hankey

    2011-05-01

    Full Text Available In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBP by small ubiquitin-related modifier (SUMO. We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immunoprecititation in all-trans retinoic acid (ATRA-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wildtype p42-C/EBPis associated with negative regulation of the myeloid specific lactoferrin (LF gene in early myeloid cells and that a reduction in p42-C/EBP sumoylation coincides with expression of the LF gene in maturing myeloid cells. In the acute promyelocytic leukemia cell line NB4 however, sumoylated p42 remains persistently bound to the LF promoter following ATRA-induction. This correlates with lack of lactoferrin expression in these cells. Changes in sumoylation status of C/EBP thus appear to contribute to a switch that regulates transcriptional activity of this master regulator during normal neutrophil development. We also demonstrate that sumoylation of the AML associated dominant negative p30-C/EBP isoform does not alter transactivation activity of the LF promoter. This may be because the p30 C/EBP isoform binds to the LF promoter much less efficiently than its full length counterpart. Our data suggest that the activity of p42-C/EBP in the developing neutrophil is more sensitive to changes in sumoylation than the p30 isoform. This difference may contribute to the leukemogenic potential of p30-C/EBP.

  18. Vitamin A deficiency modulates iron metabolism via ineffective erythropoiesis.

    Science.gov (United States)

    da Cunha, Marcela S B; Siqueira, Egle M A; Trindade, Luciano S; Arruda, Sandra F

    2014-10-01

    Vitamin A modulates inflammatory status, iron metabolism and erythropoiesis. Given that these factors modulate the expression of the hormone hepcidin (Hamp), we investigated the effect of vitamin A deficiency on molecular biomarkers of iron metabolism, the inflammatory response and the erythropoietic system. Five groups of male Wistar rats were treated: control (AIN-93G), the vitamin A-deficient (VAD) diet, the iron-deficient (FeD) diet, the vitamin A- and iron-deficient (VAFeD) diet or the diet with 12 mg atRA/kg diet replacing all-trans-retinyl palmitate by all-trans retinoic acid (atRA). Vitamin A deficiency reduced serum iron and transferrin saturation levels, increased spleen iron concentrations, reduced hepatic Hamp and kidney erythropoietin messenger RNA (mRNA) levels and up-regulated hepatic and spleen heme oxygenase-1 gene expression while reducing the liver HO-1 specific activity compared with the control. The FeD and VAFeD rats exhibited lower levels of serum iron and transferrin saturation, lower iron concentrations in tissues and lower hepatic Hamp mRNA levels compared with the control. The treatment with atRA resulted in lower serum iron and transferrin concentrations, an increased iron concentration in the liver, a decreased iron concentration in the spleen and in the gut, and decreased hepatic Hamp mRNA levels. In summary, these findings suggest that vitamin A deficiency leads to ineffective erythropoiesis by the down-regulation of renal erythropoietin expression in the kidney, resulting in erythrocyte malformation and the consequent accumulation of the heme group in the spleen. Vitamin A deficiency indirectly modulates systemic iron homeostasis by enhancing erythrophagocytosis of undifferentiated erythrocytes.

  19. DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies.

    Science.gov (United States)

    Le Pogam, Carole; Patel, Satyananda; Gorombei, Petra; Guerenne, Laura; Krief, Patricia; Omidvar, Nader; Tekin, Nilgun; Bernasconi, Elena; Sicre, Flore; Schlageter, Marie-Helene; Chopin, Martine; Noguera, Maria-Elena; West, Robert; Abu, Ansu; Mathews, Vikram; Pla, Marika; Fenaux, Pierre; Chomienne, Christine; Padua, Rose Ann

    2015-10-20

    We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers.

  20. Highly efficient differentiation and enrichment of spinal motor neurons derived from human and monkey embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Tamaki Wada

    Full Text Available BACKGROUND: There are no cures or efficacious treatments for severe motor neuron diseases. It is extremely difficult to obtain naïve spinal motor neurons (sMNs from human tissues for research due to both technical and ethical reasons. Human embryonic stem cells (hESCs are alternative sources. Several methods for MN differentiation have been reported. However, efficient production of naïve sMNs and culture cost were not taken into consideration in most of the methods. METHODS/PRINCIPAL FINDINGS: We aimed to establish protocols for efficient production and enrichment of sMNs derived from pluripotent stem cells. Nestin+ neural stem cell (NSC clusters were induced by Noggin or a small molecule inhibitor of BMP signaling. After dissociation of NSC clusters, neurospheres were formed in a floating culture containing FGF2. The number of NSCs in neurospheres could be expanded more than 30-fold via several passages. More than 33% of HB9+ sMN progenitor cells were observed after differentiation of dissociated neurospheres by all-trans retinoic acid (ATRA and a Shh agonist for another week on monolayer culture. HB9+ sMN progenitor cells were enriched by gradient centrifugation up to 80% purity. These HB9+ cells differentiated into electrophysiologically functional cells and formed synapses with myotubes during a few weeks after ATRA/SAG treatment. CONCLUSIONS AND SIGNIFICANCE: The series of procedures we established here, namely neural induction, NSC expansion, sMN differentiation and sMN purification, can provide large quantities of naïve sMNs derived from human and monkey pluripotent stem cells. Using small molecule reagents, reduction of culture cost could be achieved.