Bromelain as a natural anti-inflammatory drug: a systematic review.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

Toxicogenetic profile of the monoterpene alpha-terpineol on normal and tumor eukaryotic cells.

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 µg/mL), Artemia salina (6.25-400 µg/mL), Allium cepa (10, 50, and 100 µg/mL), comet assay (100, 200, and 500 µg/mL), cytokinesis-block micronucleus (100, 250, and 500 µg/mL), confocal microscopy for apoptosis quantification (100 and 500 µg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 µg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16-F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC50 of 68.29 and 76.36 µg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 µg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

Gastric Cancer Cell Lines Have Different MYC-Regulated Expression Patterns but Share a Common Core of Altered Genes.

MYC is an oncogene responsible for excessive cell growth in cancer, enabling transcriptional activation of genes involved in cell cycle regulation, metabolism, and apoptosis, and is usually overexpressed in gastric cancer (GC). By using siRNA and Next-Generation Sequencing (NGS), we identified MYC-regulated differentially expressed Genes (DEGs) in three Brazilian gastric cancer cell lines representing the histological subtypes of GC (diffuse, intestinal, and metastasis). The DEGs were picked using Sailfish software, followed by Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using KEGG. We found 11 significantly enriched gene sets by using enrichment score (ES), False Discovery Rate (FDR), and nominal P-values. We identified a total of 5.471 DEGs with correlation over (80%). In diffuse-type and in metastatic GC cell lines, MYC-silencing caused DEGs downregulation, while the intestinal-type GC cells presented overall DEGs upregulation after MYC siRNA depletion. We were able to detect 11 significant gene sets when comparing our samples to the hallmark collection of gene expression, enriched mostly for the following hallmarks: proliferation, pathway, signaling, metabolic, and DNA damage response. When we analyzed our DEGs considering KEGG metabolic pathways, we found 12 common branches covering a wide range of biological functions, and three of them were common to all three cell lines: ubiquitin-mediated proteolysis, ribosomes, and system and epithelial cell signaling in Helicobacter pylori infection. The GC cell lines used in this study share 14 MYC-regulated genes, but their gene expression profile is different for each histological subtype of GC. Our results present a computational analysis of MYC-related signatures in GC, and we present evidence that GC cell lines representing distinct histological subtypes of this disease have different MYC-regulated expression profiles but share a common core of altered genes. This is an important step towards the understanding of MYC's role in gastric carcinogenesis and an indication of probable new drug targets in stomach cancer.

Morfologia e morfometria da cérvice uterina de cabras sem raça definida da microrregião de Teresina-Piauí / Morphology and morphometry of the uterine cervice of cross breed goat from micro region of Teresina-Piauí

A criação de caprinos está em ascensão mundial. No Brasil, esta prática tem contribuído bastante na economia, principalmente da região Meio Norte, onde o clima predominante, o semiárido, é favorável à criação destes animais. As cabras sem raça definida (SRD) podem apresentar alterações morfofisiológicas adaptativas para viverem neste ambiente específico. As adaptações podem ocasionar modificações que fogem ao padrão geralmente observado. Na análise macroscópica foram observados trinta úteros de cabras SRD quanto a topografia, morfometria e quantificação dos anéis cervicais uterinos. Das estruturas analisadas, observaram-se diferenças apenas quanto ao número de anéis, quando comparados com outros pequenos ruminantes. A estrutura histológica da cérvice foi analisada em microscopia de luz. Este órgão é composto predominatemente por tecido conjuntivo, apresentando pouco tecido muscular. A luz do colo uterino é revestida por um epitélio pseudoestratificado com células caliciformes. A mucosa endocervical apresenta dobras longitudinais e é repleta de glândulas secretoras de muco. As camadas musculares encontram-se dispostas de forma circular (interna), longitudinal (externa) e com algumas fibras transversais. Assim, as características anatômicas da cérvice uterina de cabras sem raça definida são importantes para uma melhor execução das técnicas de manejo reprodutivo, bem como para biologia destes animais.

Goat farming is steadily increasing worldwide. In Brazil this practice have contributed a lot in the economy, especially the Mid-North region, where the semi-arid prevailing climate is favorable to the creation of these animals. To live in this environment, the cross breed goat may have morpho-physiological adaptive changes, which may cause changes that are beyond the pattern usually observed. Thirty cross breed goat uterus were selected for topographic and morphometric analysis and quantification of uteri cervical rings. In analyzed structures, differences were observed only on the number of rings when compared with others small ruminants. The histological structure of the cervix was examined under light microscopy. This body is predominately composed of connective tissue with little muscle tissue. The light of the cervix is lined by a pseudostratified epithelium with goblet cells. The endocervical mucosa has longitudinal folds and is lined with mucus-secreting glands. Muscle layers are arranged circular (internal), longitudinal (external) and some transverse fibers. Thereby, the anatomical characteristics of the uterine cervix of cross breed goats are important both to the improvement of the reproductive management techniques as to the biology of this animal.