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LC–MS characterization, anti-kinetoplastide and cytotoxic activities of natural products from Eugenia jambolana Lam. and Eugenia uniflora

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Asian Pacific Journal of Tropical Biomedicine 2017年第9期7卷 836-841页

作者： Celestina Elba Sobral de Souza Ana Raquel Pereira da Silva Janaina Esmeraldo Rocha maria celeste vega gomez Míriam Rolóm Cathia Coronel José Galberto Martins da Costa Manoel L.C.Netto Larissa A.Rolim Henrique Douglas Melo Coutinho Laboratório de Microbiologia e Biologia Molecular Universidade Regional do Cariri Center for the Development of Scientific Research Moisés Bertoni Foundation/Díaz Gill Laboratories Laboratório de Pesquisa de Produtos Naturais Universidade Regional do Cariri Centro Universitário Dr.Leao Sampaio–UNILEAO Universidade Federal do Vale do Sao Francisco–UNIVASF

Objective: To evaluate the trypanocidal, leishmanicidal and cytotoxic activity of Eugenia jambolana(E. jambolana) and Eugenia uniflora(E. uniflora) extracts and ***: The products were characterized by LC–MS. Antiparasitic assays were performed and cytotoxicity was evaluated in fibroblastos. In vitro assays were performed using spectrophotometric evaluation. All assays were performed in ***: The results showed that the extracts and the tannic fraction from E. jambolana inhibited 100% of the epimastigote lines. The ethanolic extract was the most efficient in all concentrations tested against the three parasite strains. In the cytotoxicity assay the flavonoid fraction showed low toxicity. All E. uniflora samples showed cytotoxicity at the highest concentration tested, but the extract showed no toxic effect on the fibroblasts at the lowest concentration. The flavonoid and tannic fractions were more efficient against Leishmania braziliensis promastigotes compared to the extract. However, the extracts and the tannic fraction were more effective against Leishmania infantum strains. The effect on epimastigote cells was observed at all concentrations tested, with all E. uniflora samples. However, the samples were more effective at the highest concentration, where there was inhibition in 100% of the Trypanosoma cruzi ***: The species E. jambolana and E. uniflora presented antiparasitic activity against all tested parasite strains, indicating that these species can serve as an alternative therapy as they were efficient in the tests performed. The E. uniflora extract and the E. jambolana flavonoid fraction presented a low cytotoxicity, opening the floor for new biological studies.

关键词： Antiparasitic effect Cytotoxicity Eugenia jambolana Eugenia uniflora

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Chemical composition, antiparasitic and cytotoxic activities of aqueous extracts of Ziziphus joazeiro Mart

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Asian Pacific Journal of Tropical Biomedicine 2019年第5期9卷 222-226页

作者： Jacqueline Cosmo ANDrade Ana Raquel Pereira da Silva Ant?nia Thassya Lucas dos Santos maria Audilene Freitas Yedda maria Lobo Soares de Matos maria Flaviana Bezerra Morais Braga Camila Fonseca Bezerra maria Isabeli Pereira Gon?alo maria celeste vega gomez Míriam Rolóm Cathia Coronel Paulo Riceli Vasconcelos Ribeiro Edy Sousa de Brito Henrique Douglas Melo Coutinho Microbiology and Molecular Biology Laboratory Biological Chemistry Department Regional University of Cariri-URCA Bioassays Laboratory-LABIO Federal University of Cariri-UFCA Brejo Santo University campus (CE) Center for the Development of Scientific Research Moisés Bertoni Foundation/Díaz Gill Laboratories Natural Products Chemistry Multiuser Laboratory LMQPN Embrapa Tropical Agroindustry

Objective: To compare the in vitro antiparasitic activity of aqueous extracts from Ziziphus joazeiro leaves and stem bark against Trypanosoma cruzi, Leishmania braziliensis, and Leishmania infantum, as well as to evaluate its cytotoxicity in mammalian cells, in addition to identifying the chemical composition of the extracts. Methods: Ziziphus joazeiro leaf and stem bark aqueous extracts were prepared by cold extraction maceration and subjected to ultra-efficient liquid chromatography coupled to a quadrupole/time of flight system. The susceptibility assays used Trypanosoma cruzi CLB5 strains and promastigote forms of Leishmania braziliensis and Leishmania infantum for antiparasitic activity of the extracts. Moreover, mammalian fibroblasts NCTC clone 929 were used for cytotoxicity analysis. Results: Terpenoid compounds, flavonoids and phenolic acid were identified in extracts. The stem bark aqueous extracts presented more significant results in terms of antiparasitic activity compared with the leaf aqueous extracts, especially against Leishmania braziliensis and Leishmania infantum promastigote forms with an IC50 < 500 μg/mL. The cytotoxicity evaluation showed moderate toxicity of the stem bark aqueous extracts, which is relevant information for the rational use of this plant part since it is widely used by the population. Conclusions: These preliminary results may contribute to the formulation of new therapeutic agents against this group of neglected diseases, so further investigations are required to delineate the mechanisms of action mainly of the aqueous extract of stem bark of Ziziphus joazeiro.

关键词： Antiepimastigote Antipromastigote UPLC-MS-ESI-QTOF

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Leishmaniasis in the knee area

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Asian Pacific Journal of Tropical Medicine 2010年第4期3卷 330-331页

作者： Bava Amadeo Javier Rossi maria Laura Seley celeste Troncoso Alcides Department of Micology La Plata University Department of Microbiology Parasitology and Infectious DiseasesSchool of MedicineBuenos Aires University

Leishmaniasis is a parasitic infection caused by species leishmaniae,which can produce two types of manifestations:visceral and *** south America cutaneous leishmaniasis is more common than visceral leishmaniasis.A case of primary cutaneous leishmaniasis from Bolivia is presented for its *** patient of our case showed an ulcerated lesion of the knee. Montenegro’s intradermal test was ***-stained touch preparation of the skin biopsy revealed amastigotes inside macrophages,consistent with *** patient was treated with meglumine antimoniate intramuscular(20 mg of Sb+/kg/day) three weeks,with complete cicatrization of the lesion.

关键词： Cutaneous leishmaniasis Skin ulcers Leishmania

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Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

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World Journal of Gastroenterology 2010年第21期16卷 2638-2647页

作者： Eduardo Vilar gomez Yadina Martinez Perez Hector vega Sanchez Gretel Riveron Forment Enrique Arus Soler Luis Calzadilla Bertot Ali Yasells Garcia maria del Rosario Abreu Vazquez Licet Gonzalez Fabian Department of Hepatology National Institute of GastroenterologyHavana 10400Cuba Department of Gastroenterology National Institute of GastroenterologyHavana 10400Cuba Department of Immunology National Institute of GastroenterologyHavana 10400Cuba Department of Oxidative Stress National Genetic CenterHavana 10400Cuba Department of Biostatistics National Institute of GastroenterologyHavana 10400Cuba Department of Pathology Institute of GastroenterologyHavana 10400Cuba

AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis ***:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 *** primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well ***:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

关键词： Antioxidant therapy Chronic hepatitis C Cytokines Immunomodulatory therapy Nutritional supplement Oxidative stress

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Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation

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Animal Models and Experimental Medicine 2019年第2期2卷 121-126页

作者： Sandra Simoes Rui Lopes maria celeste Dias Campos maria Joao Marruz maria Eugenia Meirinhos da Cruz Luisa Corvo Faculdade de Farmacia Instituto de Investigacao do Medicamento (iMed. ULisboa) Universidade de Lisboa Lisboa Portugal Servico de Anatomia Patologica Hospital Curry Cabral Lisboa Portugal ANATOMIK Avenida Campo Grande 168 1700‐094 Lisboa Portugal Hospital do Mar Bobadela Portugal

Acute gastric mucosal injury is a common disorder of the gastrointestinal tract and the search for new therapeutics is ongoing. The aim of this study is to update and expand the information related to the most widely used rat models of acute gastric ulcer, the ethanol‐induced ulcer and the indomethacin‐induced ulcer. These two models are compared in terms of macroscopic and microscopic features. Experimentally, ethanol was given orally in a single dose and indomethacin was subcutaneously injected into male Wistar rats. After ulcerative challenges, the stomachs were removed and visually inspected. Anti‐ulcerative drugs were used to validate the models. Histological analysis of the stomachs determined the microscopic score. The methodology used for model evaluation applied to macroscopic and microscopic gastric lesions. With these methods it was possible to induce lesions in the gastric mucosa. Microscopic evaluation permitted assessment of the inflammatory and apoptotic impact in the mucosa not observable by macroscopic evaluation. Groups of animals were treated with two standard drugs: sulcralfate suspension or lansoprazole solution. Both drugs reduced macroscopic and microscopic lesions, particularly the hemorrhagic ones. Both models induced acute gastric mucosal injury and no single evaluation method can address all the aspects of the pathology of gastric lesions. As a complement to macroscopic evaluation, microscopy appears to be a relevant tool to selectively identify specific aspects of the development of mucosal injury, quantify the extent of lesions, and contribute to an appropriate interpretation of results. The score systems established here offer a reliable method for testing antiulcer drugs.

关键词： animal models gastric ulcer histology pre-clinical assays

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Research progress on KRAS mutations in colorectal cancer

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 364-380页

作者： Marco Cefalì Samantha Epistolio maria celeste Palmarocchi Milo Frattini Sara De Dosso Department of Medical Oncology Oncology Institute of Southern SwitzerlandBellinzona 6500Switzerland Institute of Pathology Laboratory of Molecular PathologyLocarno 6600Switzerland Universitàdella Svizzera Italiana Lugano 6900Switzerland

The RAS gene family,responsible for signal transduction within the mitogen activated protein kinase(MAPK)and phosphatidylinositol 3 kinase(PI3K)pathways,is frequently involved in carcinogenesis,and alterations in its member genes can be detected,with variable frequency,in a wide variety of solid and hematological *** alterations may behave as prognostic-predictive biomarkers and driver mutations,making them an interesting therapeutic *** their discovery,many strategies have been pursued to act on their signaling ***,in clinical practice,KRAS,the most prominent member of the RAS gene family,represents an especially elusive target in most malignancies;pathway inhibition is carried out upstream,on the EGFR receptor,or downstream,most frequently on the BRAF/MEK/ERK ***,clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34G>T(p.G12C).These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS ***,their clinical relevance and appropriate place in treatment strategies remain to be determined.

关键词： KRAS targeted therapies EGFR pathway MAPK colorectal cancer

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Structural and Functional Studies of the Mitochondrial Cysteine Desulfurase from Arabidopsis thaliana

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Molecular Plant 2012年第5期5卷 1001-1010页

作者： Valeria R. Turowski maria V. Busi Diego F. gomez-Casati Centro de Estudios Fotosinteticos y Bioquimicos (CEFOBI-CONICET) Universidad Nacional de Rosario Suipacha 531 2000 Rosario Argentina and UniversidadNacional de General San Martin (UNSAM) Av. Gral Paz 5445 San Martin Buenos Aires Argentina

AtNfsl is the Arabidopsis thaliana mitochondrial homolog of the bacterial cysteine desulfurases NifS and IscS, having an essential role in cellular Fe-S cluster assembly. Homology modeling of AtNfslm predicts a high global similarity with E. coil IscS showing a full conservation of residues involved in the catalytic site, whereas the chloroplastic AtNfs2 is more similar to the Synechocystis sp. SufS. Pull-down assays showed that the recombinant mature form, AtNfslm, specifically binds to Arabidopsis frataxin （AtFH）. A hysteretic behavior, with a lag phase of several minutes, was observed and hysteretic parameters were affected by pre-incubation with AtFH. Moreover, AtFH modulates AtNfslm kinetics, increasing Vmax and decreasing the S0.5 value for cysteine. Results suggest that AtFH plays an important role in the early steps of Fe-S cluster formation by regulating AtNfsl activity in plant mitochondria.

关键词： cysteine desulfurase Fe-S biogenesis mitochondria Arabidopsis frataxin.

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Effect of Mitochondrial Dysfunction on Carbon Metabolism and Gene Expression in Flower Tissues of Arabidopsis thaliana

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Molecular Plant 2011年第1期4卷 127-143页

作者： maria V. Busi maria E. gomez-Lobato Sebastian P. Rius Valeria R. Turowski Paula Casati Eduardo J. Zabaleta Diego F. gomez-Casati Alejandro Araya Instituto de Investigaciones Biotecnologicas-lnstituto Tecnologico de ChascomOs (IIB-INTECH) CONICET/UNSAM Chascomus Argentina Centro de Estudios Fotosinteticos y Bioquimicos (CEFOBI) Universidad Nacional de Rosario Argentina Instituto de Investigaciones Biologicas liB CONICET-Universidad Nacional de Mar del Plata Argentina Microbiologie Cellulaire et Moleculaire et Pathogenicite UMR 5234 Centre National de la Recherche Scientifique and Universite Victor Segalen-Bordeaux 2 Bordeaux France

We characterized the transcriptomic response of transgenic plants carrying a mitochondrial dysfunction induced by the expression of the unedited form of the ATP synthase subunit 9. The u-ATP9 transgene driven by A9 and APETALA3 promoters induce mitochondrial dysfunction revealed by a decrease in both oxygen uptake and adenine nucleo- tides （ATP, ADP） levels without changes in the ATIP/ADP ratio. Furthermore, we measured an increase in ROS accumulation and a decrease in glutathione and ascorbate levels with a concomitant oxidative stress response. The transcriptome analysis of young Arabidopsis flowers, validated by qRT-PCR and enzymatic or functional tests, showed dramatic changes in u-ATP9 plants. Both lines display a modification in the expression of various genes involved in carbon, lipid, and cell wall metabolism, suggesting that an important metabolic readjustment occurs in plants with a mitochondrial dysfunction. Interestingly, transcript levels involved in mitochondrial respiration, protein synthesis, and degradation are affected. More- over, the levels of several mRNAs encoding for transcription factors and DNA binding proteins were also changed. Some of them are involved in stress and hormone responses, suggesting that several signaling pathways overlap. Indeed, the tran- scriptome data revealed that the mitochondrial dysfunction dramatically alters the expression of genes involved in signaling pathways, including those related to ethylene, absicic acid, and auxin signal transduction. Our data suggest that the mitochondrial dysfunction model used in this report may be useful to uncover the retrograde signaling mechanism between the nucleus and mitochondria in plant cells.

关键词： Electron transport transcriptome analysis Arabidopsis.

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Effect of synthesis variables of plasma synthesized polymers on growth of HepG2 cells

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BIOCELL 2017年第2期41卷 41-43页

作者： ELIZABETH PEREZ-TEJADA JUAN MORALES-CORONA LUIS ERNESTO gomez-QUIROZ maria CONCEPCIONGUTIERREZ-RUIZ ROBERTO OLAYO Departamento de Química.Universidad Autónoma Metropolitana Unidad IztapalapaApdo.Postal 55-534IztapalapaCDMXCP 09340 Departamento de Ciencias de la Salud.Universidad Autónoma Metropolitana Unidad IztapalapaApdo.Postal 55-534IztapalapaCDMXCP 09340 Departamento de Física.Universidad Autónoma Metropolitana Unidad IztapalapaApdo.Postal 55-534IztapalapaMéxicoD.F.CP 09340 CECyT No.8 Instituto Politécnico NacionalAve.de las Granjas 618Jardín AzpeitiaAzcapotzalcoCDMXCP 02530

Low pressure plasma polymer films were synthesized using pyrrole and allylamine monomers and adding iodine was used(or not)for the reaction in both *** were polymerized on glass substrates under the same reaction *** of allylamine was also studied at different operating *** thin polymer films were used as culture surfaces for HepG2 cells,a cell line derived from a human *** proliferation,differentiation and two-dimensional propagation until obtaining monolayer of the cells was studied on the different synthetized films and correlations were established between the conditions of synthesis,the physicochemical characteristics obtained and the performance as substrates for the cellular growth.

关键词： Hepatocytes Pyrrole Allylamine Plasma Polymerization

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Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

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Molecular Plant 2024年第6期17卷 884-899页

作者： Liping Zeng maria Fernanda gomez Mendez Jingzhe Guo Jishan Jiang Bailong Zhang Hao Chen Brandon Le Haiyan Ke Katayoon Dehesh Department of Botany and Plant Sciences Institute of Integrative Genome BiologyUniversity of CaliforniaRiversideRiversideCA 92521USA School of Medicine University of CaliforniaRiversideRiversideCA 92521USA

Stress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant *** address this,we performed a suppressor screen of the ceh1 mutant,which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate(MEcPP)levels,and identified the gain-of-function mutant impα-9,which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened *** genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1(ASK1)abundance,a pivotal component in the proteasome degradation *** increase in ASK1 prompts the degradation of IMPα-***,we uncovered a protein-protein interaction between IMPα-9 and TPR2,a transcriptional co-suppressor and found that a reduction in IMPα-9 levels coincides with a decrease in TPR2 ***,the interaction between IMPα-9 and TPR2 was disrupted in impα-9 mutants,highlighting the critical role of a single amino acid alteration in maintaining their *** of their interaction results in the reversal of MEcPP-associated *** immunoprecipitation coupled with sequencing analyses revealed that TPR2 binds globally to stress-response genes and suggested that IMPα-9 associates with the *** function together to suppress the expression of stress-response genes under normal conditions,but this suppression is alleviated in response to stress through the degradation of the suppressing *** biological relevance of our discoveries was validated under high light stress,marked by MEcPP accumulation,elevated ASK1 levels,IMPα-9 degredation,reduced TPR2 abundance,and subsequent activation of a network of stress-response *** summary,our study collectively unveils fresh insights into plant adaptive mechanisms,highlighting intricate interactions among retrograde signaling,the proteasome,and nuclear transport machinery.

关键词： plastidial retrograde signal MEcPP ASK1 impα-9 TPR2

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