Modulação da expressão de moléculas de superfície em macrófagos tratados com compostos isolados de microrganismos marinhos

Atualmente são conhecidas aproximadamente 10.000 substâncias do metabolismo secundário de invertebrados e microorganismos marinhos. Dentre os organismos marinhos estudados do ponto de vista químico e farmacológico, destacam-se, as esponjas, as ascídias, os briozoários e os octocorais. No entanto, pouco se sabe quanto ao potencial imunomodulador de compostos isolados de microrganismos marinhos, em especial daqueles isolados da costa brasileira. A propriedade anti-inflamatória de diferentes extratos brutos foi inicialmente avaliada pelo potencial destes compostos quanto à inibição da produção de óxido nítrico (NO) em linhagem de macrófagos, RAW 264.7. Posteriormente as amostras que se mostraram promissoras foram também avaliadas em relação ao potencial imunomodulador quanto a expressão de moléculas de superfície relacionadas migração (Mac-1 ou CD11b) e ativação celular (CD80 e CD86) em linhagens de macrófagos estimulados com LPS. Nossos resultados mostram que dentre as 289 amostras testadas apenas o extrato DLM33 e as substâncias Ma(M3%)J-MeOH e Dr(M3%)6-MeOH/H2O foram inicialmente considerados promissores quanto capacidade de inibir a síntese de NO por macrófagos. O extrato DLM33 foi capaz de de modular apenas a porcentagem de macrófagos positivos para CD80 na presença de LPS. No entanto, a substância Dr(M3%)6-MeOH/H2O não se mostrou eficiente quanto a modulação da expressão de moléculas de superfície Mac-1, CD80 e CD86. Surpreendentemente, a substância Ma(M3%)J-MeOH apresentou um potencial imunoestimulador quanto a expressão de Mac-1+/CD80+, mas não de CD86, em macrófagos sugerindo um possível efeito adjuvante desta substância. O efeito imunoestimulador da substância Ma(M3%)J-MeOH será futuramente investigado utilizando diferentes abordagens in vitro e in vivo para validar os resultados obtidos... (Resumo completo, clicar acesso eletrônico abaixo)

Chemical composition and antiproliferative activity of Acalypha californica

Acalypha californica Benth., is a plant in the northwestern region from Mexico, commonly known as "cancer herb" and used in traditional medicine for treating cancer. In the present study we have investigated the antiproliferative activity of methanolic extract of A. californica and its fractions in cancer cell lines and phytochemical analysis and mechanism of apoptosis of the fractions with antiproliferative activity. The antiproliferative activity of methanol extract and its fractions of solvents were evaluated by MTT assay against the M12.A(k).C3.F6, RAW 264.7, HeLa and L929 cell lines. Active fractions were fractionated by molecular exclusion chromatography, HPLC and MPLC. The identification of compounds was performed by NMR and FIA-ESI-IT-MS/MS analysis. Apoptotic mechanism was analyzed by flow cytometry, determining the reduction in the mitochondrial membrane potential (JC-1) and the activity of caspases 3,8 and 9. Cell viability assays showed that the hexane fraction of the methanol extract of the plant has significant effects against cancer lines RAW 264.7 (IC50 = 52.08 +/- 1.06 mu g/mL) and HeLa (IC50 = 46.77 +/- 1.09 mu g/mL), the residual fraction showed a selective effect on cell lines M12.A(k).C3.F6 (IC50 = 59.90 +/- 1.05 mu g/mL), RAW 264.7 (IC50 = 58.93 +/- 1.26 mu g/mL) and HeLa (IC50 = 50.11 +/- 1.135 mu g/mL) compared to the control cell line L929 (IC50 = 100.00 +/- 1.09 mu g/mL). The chemical characterization of the active fractions allowed the identification of p-sitosterol and stigmasterol in hexane fraction and some phenolic acids, proanthocyanidins and flavonoids in the residual fraction. The methanol extract and hexane fraction reduces mitochondrial membrane potential significantly and activates caspases 3, 8 and 9. Because of the antiproliferative activity observed, our results provide a rational basis for the use of extracts of A. californica in treating various types of cancer in traditional medicine from Mexico. The extracts induce apoptosis via activation of caspases. (C) 2015 Elsevier B.V. All rights reserved.

Atividade anti-inflamatória e citotoxicidade dos extratos glicólicos de Cynara cardunculus var. scolymus (L.) Fiori (alcachofra), Myracrodruon urundeuva Allemão (aroeira-do-sertão) e Camellia sinensis (L.) Kuntze (chá verde)

Pós-graduação em Biopatologia Bucal - ICT

Atividade antimicrobiana, anti-inflamatória, citotoxicidade e genotoxicidade do extrato glicólico de Betula pendula Roth (Bétula)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genistein at Maximal Physiologic Serum Levels Induces G0/G1 Arrest in MCF-7 and HB4a Cells, But Not Apoptosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Partial urethral obstruction of rabbit urinary bladder: stereological evidence that the increase in muscle content is mostly driven by changes in number, rather than size, of smooth muscle cells

The effects of partial urethral obstruction on the detrusor muscle of rabbit urinary bladder were investigated using stereological sampling and estimation tools. Twelve female Norfolk rabbits (2.5-3.0 kg body weight) were divided into four groups: 3, 7 and 12 weeks after surgical intervention to produce a standard partial obstruction and unobstructed controls. Following removal, bladder axes (craniocaudal, dorsoventral and laterolateral) and organ weights were recorded. Bladders were prepared for light microscopy by multistage random sampling procedures. Stereological methods were used to estimate the volume of muscle and the packing density and total number of myocyte nuclei in each bladder. We also estimated mean myocyte volume and the mean cross-sectional area and length of myocytes. Group comparisons were made by one-way analysis of variance. Changes in bladder axes were mainly laterolateral and craniocaudal. Mean bladder weight increased roughly six-fold by 3 weeks and 17-fold by 12 weeks and was accompanied, on average, by 12- and 33-fold increases in total muscle volume. These variables did not differ at 3 and 7 weeks post-obstruction. Increases in muscle content were not accompanied by changes in packing densities but were associated with increases in the total numbers of myocyte nuclei (13-fold by 3 weeks, 28-fold by 12 weeks). Mean myocyte volume did not vary significantly between groups but cells in obstructed groups were shorter and wider. These findings support the notion that partial outflow obstruction leads to an increase in the number, but not mean volume, of myocytes. If due solely to myocyte mitosis, the total of 43 x 10(8) cells found at 12 weeks could be generated by the original complement of 15 x 10(7) cells if an average of only 2.1 x 10(6) new cells was produced every hour. In reality, even this modest proliferation rate is unlikely to be achieved because myocyte proliferation rates are very low and it is possible that new myocytes can arise by differentiation of mesenchymal or other precursor cells.

Modelos não convencionais para estudo de interação fungo- hospedeiro e ação antifúngica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ethanolic extract of Mimosa caesalpiniifolia leaves: Chemical characterization and cytotoxic effect on human breast cancer MCF-7 cell line

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biotransformed soybean extract induces cell death of estrogen-dependent breast cancer cells by modulation of apoptotic proteins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

11-Oxoaerothionin isolated from the marine sponge Aplysina fistularis shows anti-inflammatory activity in LPS-stimulated macrophages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Patulin biodegradation using Pichia ohmeri and Saccharomyces cerevisiae

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The compulsive-like aspect of the head dipping emission in rats with chronic electrolytic lesion in the area of the median raphe nucleus

Head dipping (HD) is a behavioral pattern considered to have a risk assessment or an exploratory role and is used as a complementary parameter to evaluate anxiety in experimental animals. Since rats with electrolytic lesion in the area of the median raphe nucleus displayed high frequencies of HD in a previous study, the present investigation was undertaken to confirm this observation and to determine its anxiety-related origin. HD episodes were counted in adult male Wistar rats (270-350 g) with electrolytic lesion (N = 11) and sham-lesioned controls (N = 12). When HD was measured for 60 min on an elevated open platform, lesioned rats emitted 13 times more HD than controls (264.7 ± 93.3 vs 20.3 ± 7.6 episodes), with the difference being statistically significant (P < 0.05). HD counts during 10-min sessions held 7, 14, 21, 27, and 63 days after lesion showed significantly higher means (range: 28.14 ± 5.38 to 62.85 ± 9.48) compared to sham-lesioned controls (range: 7.37 ± 1.13 to 8.5 ± 1.45). Normal rats stepped down into their home cages when the vertical distance between them and the cage was short (16 cm), and the step-down latencies increased with increasing depths (36.7 ± 7.92 to 185.87 ± 35.44 s). Lesioned rats showed a similar behavior when facing the shortest depth, but had a significantly increased number (23.28 ± 2.35 episodes) and latency (300 ± 0.00 s) of HD compared to normal rats (9.25 ± 1.37 episodes and 185.87 ± 35.44 s) when facing the greatest depth (30 cm). This suggests that HD may be a depth-measuring behavior related to risk assessment.

Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease

Canavan disease, an inherited leukodystrophy, is caused by mutations in the aspartoacylase (ASPA) gene. It is most common among children of Ashkenazi Jewish descent but has been diagnosed in many diverse ethnic groups. Two mutations comprise the majority of mutant alleles in Jewish patients, while mutations in the ASPA gene among non-Jewish patients are different and more diverse. In the present study, the ASPA gene was analysed in 22 unrelated non-Jewish patients with Canavan disease, and 24 different mutations were found. of these,14 are novel, including five missense mutations (E24G, D68A, D249V, C152W, H244R), two nonsense mutations (Q184X, E214X), three deletions (923delT, 33del13, 244delA), one insertion mutation (698insC), two sequence variations in one allele ([10T>G; 11insG]), an elimination of the stop codon (941A>G, TAG-->TGG, X314W), and one splice acceptor site mutation (IVS1 - 2A>T). The E24G mutation resulted in substitution of an invariable amino acid residue (Glu) in the first esterase catalytic domain consensus sequence. The IVS1 - 2A>T mutation caused the retention of 40 nucleotides of intron 1 upstream of exon 2. The results of transient expression of the mutant ASPA cDNA containing these mutations in COS-7 cells and assays for ASPA activity of patient fibroblasts indicated that these mutations were responsible for the enzyme deficiency. In addition, patients with the novel D249V mutation manifested clinically at birth and died early. Also, patients with certain other novel mutations, including C152W, E214X, X314W, and frameshift mutations in both alleles, developed clinical manifestations at an earlier age than in classical Canavan disease.

Triiodothyronine mimics the effects of estrogen in breast cancer cell lines

MCF-7 (estrogen receptor positive - ER(+)) and MDA-MB-231 (estrogen receptor negative - ER(-)) are human breast cancer cell lines which express functional thyroid hormone receptors (c-erb A alpha 1 and c-erb beta 1) as indicated by stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7, mimicking E(2), T-3 stimulated growth in a dose-dependent (10(10) M-10(-8) M) manner, induced the expression of progesterone receptor and growth factor TGF alpha mRNAs and inhibited that of TGF beta mRNA; T-3 also increased progesterone binding and LDH5 isozyme activities. None of these effects were observed in (ER(-)) MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation, suppressed progesterone receptor and TGF alpha mRNA induction and restored TGF beta mRNA to control levels in T-3-treated MCF-7 cells. That T-3 is acting in MCF-7 cells via its binding to ER is suggested by the immunoprecipitation of pre-bound I-125-T-3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by the displacement of H-3-estradiol binding to ER by radioinert T-3. Copyright (C) 1996 Elsevier B.V. Ltd.