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1.
Braz. J. Pharm. Sci. (Online) ; 60: e23380, 2024. graf
Article in English | LILACS | ID: biblio-1533983

ABSTRACT

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells


Subject(s)
Peptides/adverse effects , Cells/classification , Glioblastoma/pathology , Focal Adhesion Protein-Tyrosine Kinases/adverse effects , Neoplasms/pathology , Cell Line/classification , Central Nervous System/abnormalities
2.
São Paulo; s.n; s.n; 2024. 93 p tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1563228

ABSTRACT

A quimioinformática, definida como o emprego de técnicas informáticas na solução de problemas da química, evolui em conjunto com o desenvolvimento de ferramentas computacionais e é de grande relevância para o planejamento racional de fármacos ao otimizar etapas do desenvolvimento de novas moléculas e economizar recursos e tempo. Dentre as técnicas disponíveis destacam-se o planejamento de fármacos baseado na estrutura e no ligante, que quando combinadas auxiliam na identificação e otimização de moléculas ativas frente a alvos farmacológicos. A Dihidrofolato Redutase (DHFR) é uma importante enzima da via dos folatos que catalisa a redução do dihidrofolato em tetrahidrofolato, utilizando NADPH como cofator, reação essencial para a replicação celular, visto que este ciclo resulta na síntese de precursores das bases nitrogenadas que compõem o DNA, consequentemente, inibidores de DHFR são utilizados no tratamento de infecções bacterianas e alguns tipos de câncer. Trypanosoma cruzi, protozoário causador da doença de chagas, é um dos organismos que expressam a DHFR, além do próprio Homo sapiens. Analisaram-se ligantes conhecidos e as estruturas da proteína expressa pelos dois organismos, visando identificar pontos de divergência que possam ser explorados no planejamento de moléculas seletivas para o tratamento da doença de Chagas. Os 6 modelos cristalográficos de T. cruzi e 2 de H. sapiens foram obtidos do banco de dados de proteínas (PDB) após aplicação de filtros de qualidade. Foram analisadas as sequências de aminoácidos dos modelos, com o uso do Cluster Ômega, sua estrutura tridimensional com os programas Pymol e Chimera X, além da análise das cavidades proteicas com o CavityPlus, que também gerou os farmacóforos de ambos alvos. A análise de estrutura primária identificou mutações em três aminoácidos nos cristais do parasita, que podem ser explicados por diferentes caminhos evolutivos de grupos segregados, embora nenhuma mutação observada esteja em regiões de sítio ativo. A análise dos modelos permitiu que fossem identificados os 25 aminoácidos que estão a menos de 5 Å de distância dos ligantes de T. cruzi, sendo 5 aminoácidos responsáveis por interações de hidrogênio com pelo menos um dos ligantes analisados. Destes, 18 se repetem na proteína humana ou são substituídos por outro aminoácido que mantém a mesma interação. Quanto às diferenças observadas, destacam-se a asparagina 44 substituída por uma prolina na proteína humana e a prolina 92, substituída por uma lisina. A análise de cavidades identificou três cavidades em cada proteína, embora somente as cavidades correspondentes ao sítio ativo sejam druggables. A cavidade da proteína humana é maior e mais alongada, além de apresentar o aspecto de um túnel, enquanto a cavidade da proteína parasita é mais aberta, tal abertura permite que ligantes com o anel benzeno meta substituídos explorem uma região existente na cavidade de T. cruzi que é fechada na humana. O farmacóforo de ambas proteínas foi identificado, apresentando diferenças no tamanho e angulação que também podem ser explorados no planejamento de fármacos seletivos


Chemoinformatic, defined as the use of informatic techniques to solve chemical problems, has evolved together with new computational tools and it is quite important for rational drug designing, by optimizing different steps on the development pipeline of new molecules, saving resources and time. From all the available tools, structure and ligand based drug design shall be highlighted, when combined, they support the identification and optimization of active molecules from pharmaceutical targets. Dihydrofolate reductase (DHFR) is an important enzyme of the folate pathway that catalyzes the reduction of dihydrofolate to tetrahydrofolate, by using NADPH as cofactor. This reaction is essential for cell replication, as this pathway results in the synthesis of nucleobases that build the DNA. That's the reason why DHFR inhibitors are used for treating bacterial infections and some types of cancer. Trypanosoma cruzi, a protozoa that causes Chagas disease, is one of the organisms that express DHFR, besides Homo sapiens itself. This work analyzed known ligands and the structure of the protein expressed by both organisms, aiming to identify divergence points that could be explored for designing selective drugs for Chagas disease treatment. The 6 proteins crystallographic models from T. cruzi and 2 from H. sapiens were obtained from protein data bank (PDB) after the application of quality filters. The amino acid sequence of each model was analyzed by Clustal Omega, its tridimensional structure by Pymol and Chimera X and the cavity analysis by CavityPlus, that also generated the pharmacophore from both targets. The primary structure analysis identified mutations on three amino acids on the parasite christal, which may be explained by different evolutive paths from segregated groups, although none of the observed mutations are on the active site region. The model's analysis allowed the identification of 24 amino acids that are closer than 5 Å from the T. cruzi ligands, 5 of them responsible for hydrogen interactions on at least one of the ligands analyzed. 18 of them are repeated on the human protein or are replaced by another amino acid that preserves the same interaction. As by the differences observed that shall be highlighted, asparagine 44 is replaced by a proline on the human protein, and proline 92 by a lysin. The cavity analysis identified three cavities on each protein, although only the cavities of the active site are druggables. The human protein cavity is bigger and longer, besides it looks like its a tunnel, when the parasite protein is open, that opening allows ligands with benzene ring meta substituted to explore the existing regions of the T. cruzi protein that is closed on the human protein. Lastly, the pharmacophore from both proteins was identified, it shows differences on size and angulation that also could be explored in the designing of selective drugs


Subject(s)
Pharmaceutical Preparations/analysis , Cells/classification , Cheminformatics/instrumentation , Amino Acids/agonists , Neoplasms/pathology , Asparagine/analogs & derivatives , DNA/adverse effects
3.
São Paulo; s.n; s.n; 2024. 106 p tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1570478

ABSTRACT

A via Hippo consiste em uma cascata de serina-treonina quinases que desempenha um papel central na transdução de sinais mecânicos. Em mamíferos, o eixo canônico da via consiste na ativação das quinases MST1 e MST2 (codificadas pelos genes STK4 e STK3, respectivamente) e LATS1 e LATS2. A ativação dos dois últimos culmina na fosforilação, retenção citoplasmática e inativação dos coativadores transcricionais YAP e TAZ. A inativação de Hippo resulta na localização nuclear de YAP/TAZ, aumento da proliferação e contribui para a transformação maligna em células epiteliais. No presente trabalho, identificamos que o exon 7, que codifica um segmento do domínio quinase de MST2, estava ausente em células malignas da glândula mamária humana, T4-2, mas não na linhagem não maligna, S1. A exclusão do exon 7 compromete a interação de MST2 com MOB1, um dos principais substratos de MST2. Ao contrário da proteína completa, a superexpressão de MST2 sem o exon 7 não resultou em aumento da morte celular, bem como, não diminuiu a proliferação celular. Esta nova variante de STK3/MST2, a qual denominamos STK3Δ7/MST2Δ7 é produto de um exon skipping e foi encontrada em amostras de tumores de pacientes, mas pouco predominante em amostras de tecidos normais. Além disso, em pacientes com câncer pancreático, a expressão STK3Δ7 resultou em menor sobrevida específica da doença. A retenção do exon 7 foi menor em tumores mais agressivos e com alto grau histológico. Em ensaio 3D, células não malignas com expressão ectópica de MST2Δ7 não respondem aos sinais inibitórios da membrana basal reconstituída e formam estruturas tumor-like. Esta nova variante perde sua atividade quinase e pode perturbar a homeostase tecidual pela incapacidade de ativar morte e inibir a proliferação celular, mesmo em microambientes repressores desses processos em células normais, como na presença membrana basal. Esses achados podem avançar o nosso conhecimento sobre progressão tumoral com possível relevância clínica


The Hippo pathway consists of a cascade of serine-threonine kinases that plays a central role in the transduction of mechanical signals. In mammals, the canonical axis of the pathway consists of the activation of the kinases MST1 and MST2 (encoded by the genes STK4 and STK3, respectively) and LATS1 and LATS2 and their activation culminates in the phosphorylation, cytoplasmic retention and inactivation of the transcriptional coactivators YAP and TAZ. Hippo inactivation results in nuclear localization of YAP/TAZ, increased cell proliferation, and contributes to malignant transformation in epithelial cells. In the present work, we identified that exon 7, which encodes a segment of the kinase domain of MST2, was absent in malignant cells of the human mammary gland, T4-2, but not in the non-malignant S1 cell line. Exclusion of exon 7 compromises the interaction of MST2 with one of its main substrates, MOB1. Unlike the full-length protein, overexpression of MST2 without exon 7 did not result in increased cell death, nor decreased cell proliferation. This new variant of STK3/MST2, which we named STK3Δ7/MST2Δ7, is the product of an exon skipping and was found in tumor samples, but seldomly found in samples of normal tissues. Furthermore, in patients with pancreatic cancer, STK3Δ7 expression resulted in lower disease-specific survival. Exon 7 retention was reduced in aggressive tumors with a high histological grade. In a 3D assay, non-malignant cells with ectopic expression of MST2Δ7, even at low concentrations, do not respond to inhibitory signals from a reconstituted basement membrane and form tumor-like structures. This new variant loses its kinase activity and may disturb the tissue homeostasis due to its inability to activate death and to inhibit cell proliferation, even in microenvironments that repress these processes in normal cells, such as the basement membrane. These findings may advance our knowledge about tumor progression and might be clinically relevant


Subject(s)
Pancreatic Neoplasms/pathology , Cell Proliferation , Hippo Signaling Pathway , Cells/classification , Cell Death/immunology , Protein Serine-Threonine Kinases , Epithelial Cells/classification , Ectopic Gene Expression
4.
Braz. J. Pharm. Sci. (Online) ; 59: e23259, 2023. tab, graf
Article in English | LILACS | ID: biblio-1520310

ABSTRACT

Abstract Lung cancer is a major cause of cancer-related death worldwide. This study investigated the regulatory effects of the microRNA-99a-5p (miR-99a-5)/VLDLR axis on lung cancer cell sensitivity to chemotherapy and its mechanism. miR-99a-5p and VLDLR expression levels were quantified using RT-qPCR and western blotting, respectively. The IC50 value of cisplatin (DDP) was determined using a CCK-8 assay. Lung cancer cell proliferation and apoptosis were measured using the CCK-8 assay and flow cytometry, respectively. The mRNA expression levels of apoptosis-related factors (Bax, Bcl-2, and Caspase-3) were evaluated using RT-qPCR. The direct relationship between miR-99a-5p and VLDLR was validated using dual-luciferase reporter gene and RIP assays. miR-99a-5p was weakly expressed in DDP-resistant lung cancer cells. Overexpression of miR-99a-5p promoted DDP sensitivity, suppressed proliferation and colony formation, and promoted apoptosis of A549/DDP cells in vitro. Mechanistically, miR-99a-5p restrained VLDLR expression by binding to VLDLR 3'UTR, and miR-99a-5p mediated inhibition of VLDLR regulated the DDP sensitivity, proliferation, and apoptosis of A549/ DDP cells. Overexpression of miR-99a-5p inhibited the growth of A549 cells and increased chemosensitivity of A549 cells to DDP in vivo. In conclusion, miR-99a-5p overexpression promotes sensitivity to DDP and cell apoptosis by downregulating VLDLR expression in A549/ DDP cells.


Subject(s)
Humans , Animals , Male , Female , Mice , Apoptosis , Drug Therapy , Lung Neoplasms/pathology , Sincalide , In Vitro Techniques/methods , Cells/classification , Blotting, Western/methods , Cell Proliferation , Flow Cytometry/instrumentation
5.
Braz. J. Pharm. Sci. (Online) ; 58: e20039, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403719

ABSTRACT

Abstract The consumption of cosmetics has been increasing every year and is expected to reach $675 billion by 2020 at an estimated growth rate of 6.4% per year. Exposure to skin irritants is the major cause of non-immunological inflammation of the skin. Therefore, the safety evaluation of cosmetic preservatives should be increased. Thus, the present work aimed to evaluate the cytotoxicity as the viability endpoint and the eye irritation potential of preservatives used in cosmetics. Cytotoxicity assays were performed using MTT and NRU in human keratinocytes (HaCaT), human dermal fibroblasts, adult (HDFa), and human hepatoma cells (HepG2). The eye irritation potential was evaluated using the Hen's Egg Test-chorioallantoic membrane (HET-CAM). The evaluated preservatives were methylparaben (MP), propylparaben (PP), phenoxyethanol (PE), and a mixture of methylchloroisothiazolinone and methylisothiazolinone (CMI/MI). All preservatives showed cytotoxic potential within the permitted concentrations for use in cosmetic products. In the HET-CAM test, PE and CMI/MI, MP, and PP were classified as severe, moderate, and poor irritants, respectively. Our results indicate that proper safety evaluations are required to ensure the beneficial properties of preservatives on cosmetic products without exceeding exposure levels that would result in adverse health effects for consumers.


Subject(s)
In Vitro Techniques/methods , Cosmetics/analysis , Additives in Cosmetics , Safety , Skin/injuries , Cells/classification , Health , Inflammation/complications , Irritants/pharmacology
6.
Braz. J. Pharm. Sci. (Online) ; 58: e19221, 2022. tab, graf
Article in English | LILACS | ID: biblio-1374557

ABSTRACT

Abstract The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor


Subject(s)
Cells/classification , Cytochrome P-450 CYP1A2/analysis , Genotoxicity , Cell Line/classification , Hydroxylamine/agonists , DNA Repair
7.
São Paulo; s.n; s.n; 2022. 86 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1378701

ABSTRACT

Responsável por milhões de óbitos anuais e um grande custo para a saúde pública, o câncer é a segunda maior causa de mortes no mundo. Dentre seus diversos tipos, o câncer de pulmão, além da alta incidência, é um dos mais letais. A exposição a substâncias tóxicas provenientes da combustão de matéria orgânica, assim como o consumo de cigarro, são os principais responsáveis pela alta incidência de câncer de pulmão. Dentre estas substâncias, está o benzo[α]pireno (B[α]P), um carcinógeno completo, ou seja, capaz de iniciar e promover o processo de carcinogênese. Resultados anteriores obtidos pelo grupo demonstraram que células BEAS-2B expostas a 1 µM de B[α]P apresentaram alterações das concentrações de metabólitos intracelulares, indução de estresse redox e hipermetilação do DNA. A exposição a 1 µM de nicotinamida ribosídeo (NR), um dos precursores de NAD+, foi capaz de proteger as células BEAS-2B contra a transformação induzida por B[α]P, além de impedir totalmente que células não expostas a B[α]P formassem colônias em soft-agar. A utilização da proteômica neste trabalho permitiu verificar a abundância das proteínas nos quatro diferentes grupos de exposição: Controle, B[α]P, B[α]P + NR e NR. Após 120 h de exposição as células foram coletadas, as proteínas extraídas e preparadas para análise. Foram descobertas 3024 proteínas posteriormente analisadas com o objetivo de elucidar vias possivelmente envolvidas na proteção contra o processo de transfomação maligna. Os grupos NR e Controle demonstram ser mais parecidos em relação ao seu conteúdo, enquanto os grupos B[α]P e B[α]P + NR foram mais semelhantes entre si. A análise de proteínas exclusivas revelou menos processos relacionados ao reparo de DNA no grupo tratado apenas com B[α]P quando comparado com B[α]P + NR. A análise estatística do total de proteínas utilizando o teste ANOVA (p < 0,05, N = 5) revelou 564 proteínas diferencialmente expressas entre os grupos. A clusterização nos permitiu observar a diferença na abundância de proteínas entre os quatro tratamentos. As proteínas estão envolvidas em funções como a regulação do metabolismo, resposta a estresse, transdução de sinal, regulação de expressão gênica e morte celular. Um dos clusters (cluster 1), contendo 59 proteínas, revelou poucos processos na análise de enriquecimento, mas as proteínas contidas nele apresentam funções como controle da divisão celular, apoptose e proteção ao estresse redox. Nele podemos observar que, no geral, o tratamento com B[α]P aumentou a abundância de algumas proteínas, o que foi revertido no grupo B[α]P + NR. O tratamento apenas com NR diminuiu a abundância das proteínas contidas nesse cluster. Outro cluster (cluster 4) apresentou 51 proteínas de abundância diminuída durante a exposição ao B[α]P, o que se reverteu no grupo B[α]P + NR. As proteínas desse cluster estão envolvidas em etapas importantes da via glicolítica, de crescimento, adesão, migração e invasão celular. Apesar de ser descrito que a exposição a NR pode aumentar a eficiência do reparo de DNA, os resultados apresentados nesse trabalho indicam que o efeito protetor pode estar relacionado com a modulação do ciclo celular ou alterações na adesão celular


Responsible for millions of annual deaths and a great health expense, cancer is the second leading cause of death in the world. Among its many types, lung cancer, besides its high incidence, is also one of the most lethal. Exposure to toxic substances resulting from the combustion of organic matter, as well as cigarette consumption, are the mainly responsible for the high incidence of lung cancer. One of these substances is benzo[α]pyrene (B[α]P), a complete carcinogen, able to initiate and promote the carcinogenesis process. Results obtained previously demonstrated that BEAS-2B cells exposed to 1 µM BaP presented alterations in the levels of intracellular metabolites, induction of oxidative stress, and hypermethylation of DNA. The exposure to 1 µM nicotinamide riboside (NR), one of the precursors of NAD+, was able to protect BEAS-2B cells against the transformation induced by B[α]P, moreover, it also totally prevented the colonies formation on soft agar in cells not exposed to B[α]P. The use of proteomics allowed us to verify the abundance of proteins in the four different exposure groups: Control, B[α]P, B[α]P + NR e NR. After 120h of exposure, the cells were collected followed by the extraction of the proteins. A total of 3024 proteins were identified and analyzed aiming to elucidate possible pathways involved in the protective effect against the malignant transformation induced by B[α]P. The NR and Control groups showed to be more similar, while B[α]P and B[α]P + NR were more similar. The analysis of exclusive proteins revealed fewer processes related to DNA repair in B[α]P when compared with B[α]P + NR. The statistical analysis of the total proteins using the ANOVA test (p <0.5, N = 5) revealed 564 proteins differentially expressed between the groups. The heatmap showed the difference in protein abundance between the four treatments. Proteins are involved in functionssuch asthe regulation of metabolism, stress response, signal transduction, regulation of gene expression, and cell death. One of the clusters (cluster 1), containing 59 proteins, revealed a few processes in the enrichment analysis, but the proteins contained in it have functions such as control of cell division, apoptosis, and protection from redox stress. It is possible to observe, in general, treatment with B[α]P increased the abundance of some proteins, which was partially reversed in group B[α]P + NR. On the other hand, the NR treatment decreased the abundance of proteins contained in this cluster. Another cluster (cluster 4) showed 51 proteins of decreased abundance during exposure to B [α] P, which was partially reversed in group B[α]P + NR. The proteins in this cluster are involved in important stages of the glycolytic pathway, also in growth, adhesion, migration, and cell invasion. Although it has been described that exposure to NR can increase the efficiency of DNA repair, the results presented in this work indicate that the protective effect may be related to the modulation of the cell cycle or cell adehsion modifications


Subject(s)
Proteomics/classification , Tobacco Products/classification , Carcinogenesis , Neoplasms , Cells/classification , Analysis of Variance , Data Interpretation, Statistical , Cell Death , Niacinamide/agonists , Oxidative Stress , Lung Neoplasms/pathology
8.
Braz. J. Pharm. Sci. (Online) ; 57: e18497, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339303

ABSTRACT

Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties


Subject(s)
Cells/classification , Neoplasms , Organization and Administration , Biological Products/adverse effects , DNA , Cell Line , HCT116 Cells/classification , Cytostatic Agents/pharmacology , Hydrophobic and Hydrophilic Interactions
9.
Braz. J. Pharm. Sci. (Online) ; 56: e18499, 2020. tab, graf
Article in English | LILACS | ID: biblio-1285512

ABSTRACT

Lignosus rhinocerotis (tiger milk mushroom) is widely used by the indigenous people of Malaysia as a traditional remedy. The present study was carried out in order to evaluate the antioxidant, cytotoxic and anti-neuroinflammatory activities of L. rhinocerotis extract on brain microglial cells (BV2). The antioxidant activity was evaluated by 2,2-diphenyl-1-picryhydrazyl (DPPH•), 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS•+) scavenging assays, and ferric reducing antioxidant power (FRAP). The FRAP, DPPH and ABTS•+ scavenging capacities of the TE3 fraction were 420.77 mg FE/g, 58.01%, and 7%, respectively. The cytotoxic activity was determined by MTS assay. The in vitro model of anti-neuroinflammatory property was evaluated by measuring the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced BV2 cells. The TE3 fraction showed a significant NO reduction at 1 to 100 µg/mL. The TE3 fraction down-regulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) genes while it upregulated heme oxygenase (HO-1) and NADPH quinone acceptor oxidoreductase-1 (NQO-1) genes. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription was also activated. The chemical component of the active fraction (TE3) was identified by gas chromatography-mass spectrometry (GCMS). Overall, the BV2 in vitro model anti-neuroinflammatory activity of L. rhinocerotis may be caused by the lipid constituents identified in the fraction


Subject(s)
In Vitro Techniques/methods , Cells/classification , Agaricales/classification , Inflammation/drug therapy , Lipids/adverse effects , Gas Chromatography-Mass Spectrometry/instrumentation , Antioxidants/pharmacology
11.
In. Boggia, José; López, Alejandra; Bianchi, Sergio; Noboa, Oscar; Gadola, Liliana; Briva, Arturo; Hurtado, Javier; Grignola, Juan Carlos; Rodríguez, MaríaJosé. Fisiopatología: mecanismos de las disfunciones orgánicas. Montevideo, Oficina del Libro FEFMUR, 2a. ed; 2011. p.53-102.
Monography in Spanish | LILACS | ID: lil-759797
12.
Nova York; John Wiley e Sons Inc; 6th ed; 2010. 732 p.
Monography in English | LILACS | ID: lil-766493
13.
Nova York; John Wiley e Sons Inc; 6th ed; 2010. 732 p.
Monography in English | LILACS, ColecionaSUS | ID: biblio-941510
14.
New Jersey; Wiley and Sons; 5th ed; 2005. 642 p.
Monography in English | LILACS | ID: lil-760615
15.
New Jersey; Wiley and Sons; 5th ed; 2005. 642 p.
Monography in English | LILACS, ColecionaSUS | ID: biblio-940951
16.
Porto Alegre; Artmed; 4. ed; 2004. 1463 p. ilus.
Monography in Portuguese | LILACS | ID: lil-583176
17.
Rev. obstet. ginecol. Venezuela ; 59(3): 181-7, sept. 1999. ilus
Article in Spanish | LILACS | ID: lil-270035

ABSTRACT

Estudiar la interacción de la matriz extracelular con membranas plasmáticas de células fetales y maternas con microscopía electrónica de trasmisión y microscopía electrónica de barrido complementada por histoquímica ultraestructural usando azul alcián. Imágenes simultáneas de microfotografías con microscopía electrónica de trasmisión y microscopía electrónica de barrido son correlacionadas en sectores de membranas con relación a la matriz extracelular teñida con azul alcián. Centro de Investigación y Análisis Docente Asistencial del Núcleo Aragua. Facultad de Ciencias de la Salud. Universidad de Carabobo. Maracay-Venezuela. Microfilamentos conectan matriz hipoplasmática con matriz extracelular por intermedio de la membrana. Matriz extracelular de aspecto gránulo-filamentoso; se notó en dos tonalidades contrastadas, granulos electrón densos de células deciduales o trofoblásticas se observan en la periferia celular. Fibrina, colágena degenerada, fibrinoide y gránulos de diversos tamaños conforman una red compleja en el espacio extracelular. Fibrinoide tipo matriz fue reactivo al azul alcián y conforma parte del espacio extracelular observado simultáneamente con imágenes de microscopía electónica de trasmisión y microscopía electrónica de barrido a baja resolución, donde reacciones fisiológicas son de notable importancia clínica


Subject(s)
Humans , Female , Pregnancy , Placenta/cytology , Extracellular Matrix/physiology , Fetus , Mothers , Cells/classification , Microscopy, Electron, Scanning/methods
18.
Vet. Méx ; 30(2): 143-7, abr.-jun. 1999. ilus, tab
Article in Spanish | LILACS | ID: lil-276984

ABSTRACT

Diversos hallazgos experimentales sugieren la participación de las hormonas esteroides ováricas sobre la regulación de la población de células cebadas (CC) en órganos del aparato reproductor femenino. Con el propósito de conocer la distribución de la población de células cebadas en tres porciones anatómicas del cuello uterino (CU) de cerdas con diferentes características morfológicas ováricas, se estudiaron los CU de 20 cerdas púberes clínicamente sanas, 10 con desarrollo folicular y las restantes con cuerpo lúteo funcional. Se tomaron fragmentos de 2 cm2 de los segmentos craneal, medio y caudal del CU y se procesaron mediante la técnica de inclusión en parafina. Los cortes fueron teñidos con azul de tolouidina y posteriormente se contaron las CC presentes por mm2. Hubo diferencia estadística significativa (P< 0.05) entre los tres segmentos anatómicos estudiados, en las dos fases del ciclo estral, resultando una mayor cantidad de CC en el CU de cerdas con desarrollo folicular respecto de las cerdas con cuerpo lúteo. En cada fase se encontró diferencia significativa entre el segmento craneal con respecto a los dos segmentos anatómicos restantes. Estos resultados sugieren que la dinámica funcional de las CC del CU de la cerda varía dependiendo de su porción anatómica y de la condición morfofuncional ovárica que predomina en determinado momento del ciclo estral


Subject(s)
Animals , Swine/physiology , Cervix Uteri/cytology , Cells/classification , Corpus Luteum/physiology , Ovarian Follicle/cytology , Ovary/physiology , Steroids/physiology , Estrus/physiology
19.
Rev. méd. cient. San Gabriel ; 3(1): 24-30, 1996. ilus
Article in Spanish | LILACS | ID: lil-238424

ABSTRACT

Se describe un caso de fibrotecoma de ovàrio en una mujer de 48 años, con la presencia de tumoraciòn pèlvica dolorosa y ascitis. Microscopicamente muestra la presencia de cèlulas fusiformes con disposiciòn entrecruzada sin mitosis anormales entremezcladas con nidos de cèlulas tecales. Tumor que se origina en el estroma ovàrico raras veces en un fibroma de, consistencia dura, al corte con aspecto arremolinado blanquesino, con tonos amarillentos, benigno


Subject(s)
Humans , Female , Pregnancy , Ascites/diagnosis , Struma Ovarii/diagnosis , Fibroma/diagnosis , Ovary/growth & development , Cells/classification , Hydrothorax/diagnosis
20.
Arch. venez. farmacol. ter ; 13(2): 81-6, 1994.
Article in Spanish | LILACS | ID: lil-238581

ABSTRACT

La relación existente entre insulino-resistencia, hiperinsulinemia e hipertensión es bien conocida, pero la correlación entre estas no prueba que se trata de una interrelación causal. Ha sido postulado que la insulino-resistencia y la hiperinsulinemia compensadora, contribuyen a la patogénesis de la hipertensión, posiblemente estimulando el sistema nervioso simpático, promoviendose la reabsorción de sodio, modulando el transporte de cationes y/o estimulando la hipertrofia del músculo liso vascular. Es nuestro propósito en esta revisión examinar críticamente la hipótesis de la insulinoresistencia-hiperinsulinemia-hipertensión


Subject(s)
Humans , Male , Female , Middle Aged , Cells/classification , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Hyperinsulinism/diagnosis , Insulin/administration & dosage
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