Malignancy Associated with Low-Risk HPV6 and HPV11: A Systematic Review and Implications for Cancer Prevention.

High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.

Antitumor Effect of Açaí (Euterpe oleracea Mart.) Seed Extract in LNCaP Cells and in the Solid Ehrlich Carcinoma Model.

Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins-polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects-almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties.

Effects of Euterpe oleracea Mart. extract on Candida spp. biofilms.

PROBLEM OF RESEARCH: Candida spp. biofilms are complex microbial communities that have been associated with increasing resistance to clinically available antifungal drugs. Hence, novel pharmacological approaches with ability to inhibit biofilm formation have been investigated. AIM OF STUDY: The aim was to analyze in vitro antifungal activity of Euterpe oleracea Mart. (açaí berry) extract on biofilm strains of Candida albicans, C. parapsilosis, and C. tropicalis that were formed on abiotic surfaces. REMARKABLE METHODOLOGY: Biofilms of C. albicans, C. parapsilosis, and C. tropicalis were grown in vitro. They were then treated with E. oleracea Mart. extract at different concentrations (7.8, 15.6, 31.2, 62.5, 125, 250, 500, and 1000 µg/mL) for evaluation of both biofilm removal and anti-biofilm activity. REMARKABLE RESULTS: All Candida species analyzed formed biofilms on abiotic surfaces. Yet, increased biofilm formation was displayed for C. tropicalis in comparison with the other two species. E. oleracea Mart. extract was shown to inhibit biofilm formation at all concentrations used when compared to no treatment (p < 0.05). SIGNIFICANCE OF THE STUDY: In the current study, the extract of E. oleracea Mart. demonstrated antifungal activity against Candida albicans, C. parapsilosis, and C. tropicalis biofilms, regardless of the dose utilized. These results are important to evaluate a natural product as antifungal for Candida species.

Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins.

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

Inhibitory Effect of Catechin-Rich Açaí Seed Extract on LPS-Stimulated RAW 264.7 Cells and Carrageenan-Induced Paw Edema.

Açaí berry is a fruit from the tree commonly known as açaízeiro (Euterpe oleracea Mart.) originated from the Amazonian region and widely consumed in Brazil. There are several reports of the anti-inflammatory activity of its pulp and few data about the seed's potential in inflammation control. This work aimed to evaluate the effect of catechin-rich açaí extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-induced paw edema. The treatment with E. oleracea ethyl acetate extract (EO-ACET) was used in an in vitro model performed with macrophages stimulated by LPS, in which pro-inflammatory markers were evaluated, and in an in vivo model of acute inflammation, in which edema inhibition was evaluated. EO-ACET showed an absence of endotoxins, and did not display cytotoxic effects in RAW 264.7 cells. LPS-stimulated cells treated with EO-ACET displayed low levels of nitrite and interleukins (IL's), IL-1ß, IL-6 and IL-12, when compared to untreated cells. EO-ACET treatment was able to inhibit carrageenan-induced paw edema at 500 and 1000 mg/kg, in which no acute inflammatory reaction or low mast cell counts were observed by histology at the site of inoculation of λ-carrageenan. These findings provide more evidence to support further studies with E. oleracea seeds for the treatment of inflammation.

GC-MS Characterization of Antibacterial, Antioxidant, and Antitrypanosomal Activity of Syzygium aromaticum Essential Oil and Eugenol.

Syzygium aromaticum has a diversity of biological activities due to the chemical compounds found in its plant products such as total phenolic compounds and flavonoids. The present work describes the chemical analysis and antimicrobial, antioxidant, and antitrypanosomal activity of the essential oil of S. aromaticum. Eugenol (53.23%) as the major compound was verified by gas chromatography-mass spectrometry. S. aromaticum essential oil was more effective against S. aureus (MIC 50 µg/mL) than eugenol (MIC 250 µg/mL). Eugenol presented higher antioxidant activity than S. aromaticum essential oil, with an EC50 of 12.66 and 78.98 µg/mL, respectively. S. aromaticum essential oil and eugenol exhibited Trypanosoma cruzi inhibitory activity, with IC50 of 28.68 ± 1.073 and 31.97 ± 1.061 µg/mL against epimastigotes and IC50 of 64.51 ± 1.658 and 45.73 ± 1.252 µg/mL against intracellular amastigotes, respectively. Both compounds presented low cytotoxicity, with S. aromaticum essential oil displaying 15.5-fold greater selectivity for the parasite than the cells. Nitrite levels in T. cruzi-stimulated cells were reduced by essential oil (47.01%; p = 0.002) and eugenol (48.05%; p = 0.003) treatment. The trypanocidal activity of S. aromaticum essential oil showed that it is reasonable to use it in future research in the search for new therapeutic alternatives for trypanosomiasis.

Highly efficient antibiofilm and antifungal activity of green propolis against Candida species in dentistry materials.

This study evaluated the effect of green propolis extract on the adhesion and biofilm formation of Candida species in dentistry materials. Phytochemical analysis of green propolis extract was performed by high-performance liquid chromatography. Adhesion was quantified by counting the number of yeast cells adherent to dental material fragments in a Neubauer chamber. Biofilm formation was determined by counting colony-forming units recovered from dental material fragments. The intensity of biofilm adhesion was classified as negative, weak, moderate, strong, or very strong. Fifteen compounds, mainly flavonoids, were identified in green propolis extract. All strains adhered to and formed biofilms on the surfaces of the orthodontic materials studied. On steel and resin, yeast cell adhesion intensities were weak at all incubation times, except for those of Candida parapsilosis and C. tropicalis, which were moderate at 12 h. At 24 and 48 h, C. albicans formed biofilms on steel with moderate adhesion affinities; at 24 and 48 h, C. parapsilosis formed biofilms with very strong affinities. C. tropicalis formed biofilms with strong and very strong affinities at 24 and 48 h, respectively. On resin, all species displayed strong affinity for biofilm formation at 24 and 48 h, except for C. tropicalis, which displayed very strong affinity at only 48 h. Green propolis extract displayed antifungal activity and inhibited both adhesion and biofilm formation at 2.5 µg/mL. This study reinforces the idea that green propolis has antifungal activity and interferes with the virulence of Candida species.

Caracterização química, atividade antimicrobiana e toxicidade dos óleos essenciais da Pimenta dioica L. (pimenta da Jamaica) e Citrus sinensis L. Osbeck (laranja doce) / Chemical characterization, antimicrobial activity, and toxicity of the essential oils of Pimenta dioica L. and Citrus sinensis L. Osbeck (laranja doce)

RESUMO Este estudo avaliou a toxicidade e a atividade antimicrobiana frente a Escherichia coli e Staphylococcus aureus dos óleos essenciais de Pimenta dioica Lindl. e Citrus sinensis L. Os óleos essenciais (OE) foram extraídos por hidrodestilação, com caracterização química através de cromatografía gasosa acoplada a espectrometria de massas (CG-EM). Os parâmetros físico-químicos foram determinados de acordo com a Farmacopeia Brasileira. O ensaio de toxicidade seguiu o bioensaio com Artemia salina Leach, os OE aprovados neste ensaio seguiram para avaliação das suas propriedades biológicas. A atividade antimicrobiana seguiu a metodologia descrita pelo Clinical and Laboratory Standards Institute utilizando o método de difusão de disco, diluição em caldo para concentração inibitória mínima (CIM) e posterior concentração bactericida mínima para avaliar a ação dos OE frente a Escherichia coli e Staphylococcus aureus. Ambos os OE apresentaram toxicidade baixa, e assim foram avaliados quanto as propriedades biológicas antimicrobianas. Ambos os OE apresentaram potenciais bactericidas frente aos microrganismos testados, exibindo resultados satisfatórios para a ação deles. Os resultados indicam que os OE avaliados são compostos por substâncias que propiciam e incentivam sua aplicação em virtude de seus potenciais para atividade biológicas moluscicida e antimicrobiana.

SUMMARY This study evaluated the toxicity and antimicrobial activity in the face of Escherichia coli and Staphylococcus aureus of essential oils of Pimenta dioica Lindl. and Citrus sinensis L. The essential oils (EO) were extracted by hydrodistillation, with chemical characterization by gas chromatography coupled and mass spectrometry (GC-MS). Physicochemical parameters were determined according to the Brazilian Pharmacopeia. The toxicity test followed the bioassay with Artemia salina Leach, the EO approved in this assay followed to evaluate its biological properties. The antimicrobial activity followed the methodology described by the Clinical and Laboratory Standards Institute using the disc diffusion method, broth dilution for minimum inhibitory concentration (MIC) and subsequent minimum bactericide concentration for to evaluate the action of EO against Escherichia coli and Staphylococcus aureus. Both OE showed low toxicity, and thus were evaluated for the biological antimicrobial properties. Both OE presented bactericidal potential against the microorganisms tested, showing satisfactory results for their action. The results indicate that the evaluated OE are composed of substances that provide and encourage their application due to their potentials for biological molluscicide and antimicrobial activity.

Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model.

BACKGROUND: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. METHODS: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL-), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. RESULTS: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. CONCLUSIONS: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.

Aniba rosaeodora (Var. amazonica Ducke) Essential Oil: Chemical Composition, Antibacterial, Antioxidant and Antitrypanosomal Activity.

Aniba rosaeodora is one of the most widely used plants in the perfumery industry, being used as medicinal plant in the Brazilian Amazon. This work aimed to evaluate the chemical composition of A. rosaeodora essential oil and its biological activities. A. rosaeodora essential oil presented linalool (93.60%) as its major compound. The A. rosaeodora essential oil and linalool showed activity against all the bacteria strains tested, standard strains and marine environment bacteria, with the lower minimum inhibitory concentration being observed for S. aureus. An efficient antioxidant activity of A. rosaeodora essential oil and linalool (EC50: 15.46 and 6.78 µg/mL, respectively) was evidenced by the inhibition of the 2,2-azinobis- (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. The antitrypanosomal activity of A. rosaeodora essential oil and linalool was observed at high concentrations against epimatigote forms (inhibitory concentration for 50% of parasites (IC50): 150.5 ± 1.08 and 198.6 ± 1.12 µg/mL, respectively), and even higher against intracellular amastigotes of T. cruzi (IC50: 911.6 ± 1.15 and 249.6 ± 1.18 µg/mL, respectively). Both A. rosaeodora essential oil and linalool did not exhibit a cytotoxic effect in BALB/c peritoneal macrophages, and both reduced nitrite levels in unstimulated cells revealing a potential effect in NO production. These data revealed the pharmacological potential of A. rosaeodora essential oil and linalool, encouraging further studies.

Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa Essential Oils: Chemical Composition, Antimicrobial and Antileishmanial Activity.

The resistance mechanisms of bacteria and protozoans have evidenced the need of discover new compounds with potential pharmaceutical activity against pathogenic microorganisms. Medicinal plants have been for centuries a promising alternative as sources of new drugs. The objective of this work was to evaluate the chemical composition, antimicrobial and antileishmanial activities of Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa essential oils. Chemical analysis was performed by gas chromatography-mass spectrometry. Antimicrobial activity was performed by disk diffusion and minimum inhibitory concentration (MIC) test. Antileishmanial activity was performed against antipromastigote and intracellular amastigote of Leishmania amazonensis. Cytotoxic and nitrite production were realized in BALB/c peritoneal macrophages. The major compounds of the essential oils were cinnamic aldehyde (46.30%) in C. zeylanicum, cis-p-menth-2-en-1-ol (33.88%) and linalyl acetate (13.90%) in O. vulgare, and turmerone (55.43%) in C. longa. The MIC showed significant antimicrobial activity of C. longa essential oil against S. aureus (83.3 ± 14.43 µg/mL). Antipromastigote activity showed IC50 values >500 µg/mL to C. zeylanicum, 308.4 ± 1.402 µg/mL to O. vulgare, and 405.5 ± 1.119 µg/mL to C. longa essential oil. Activity against intracellular amastigote of L. amazonensis showed IC50 of 63.3 ± 1.369 µg/mL and cytotoxic was not observed, resulting in selectivity index higher than 15.79 to parasite. C. longa essential oil decreased nitrite production in peritoneal macrophages, but not in Leishmania-infected cells. The chemical composition of the three essential oils is directly associated to its potential biological action, as the antimicrobial activity. C. longa presented a potent antileishmanial activity against promastigote and intracellular amastigote of L. amazonensis, although this activity is not linked to nitric oxide, since C. longa essential oil inhibits its production.

Quantificação e identificação de Staphylococcus coagulase positiva e negativa em leites cru e pasteurizado comercializados na cidade de São Luís ­ MA / Quantification and identification of positive and negative Staphylococcus coagulase in raw and pasteurized milks marketed in the city of São Luís - MA

A qualidade microbiológica deleites cru e pasteurizado produzidos e comercializados em São Luís ­ MA foi avaliada por meio da quantificação e identificação de cepas de micro-organismos do gênero Staphylococcus. Verificou-se um alto nível de contaminação por Staphylococcus sp. em 60% das amostras de leite cru analisadas, com as contagens variando entre 1,7x105 e 1,1x107 UFC/mL, sendo comprovada a presença de Staphylococcus coagulase positiva nessas amostras. No leite pasteurizado foram obtidas baixas contagens desse micro-organismo, com valores variando entre 2,7x102 e 4,2x102 UFC/mL, não sendo detectados Staphylococcus coagulase positiva, apenas coagulase negativa em 23% (n=3) das amostras analisadas. As colônias características de Staphylococcus isoladas foram identificadas por meio de testes bioquímicos convencionais. Das 50 cepas isoladas, 38% foram positivas para o teste de coagulase, sendo identificadas as espécies S. aureus, S. hyicus, S. intermedius e S. delphini. Entre as cepas de Staphylococcus coagulase negativa, verificou-se a predominância das espécies S. gallinarum, S. cloosii, e S. xylosus. A presença de tais micro-organismos no leite é preocupante do ponto de vista da segurança dos alimentos, tendo em vista que espécies como S. aureus, S. hyicus e S. intermedius são potenciais produtoras de enterotoxinas termoestáveis.

The microbiological quality of raw and pasteurized milk produced and sold in São Luís ­ MA was evaluated through quantification and identification of Staphylococcus cepes. A high level contamination by Staphylococcus sp. was verified in 60% of samples of raw milk, counting varying between 1.7 × 105 e 1.1 × 107 CFU/mL, which proves the presence of positive coagulasis Staphylococcus in these samples. In the pasteurized milk low counting of this microorganism was obtained, values varying between 2.7 × 102 e 4.2 × 102 CFU/mL, in where it was not found positive coagulase Staphylococcus, but only negative ones in 23% (n=3) of the analyzed samples. The typical colonies of isolated Staphylococcus were identified through conventional biochemical tests. From 50 isolated cepes, 38% were positive for coagulase test, in which S. aureus, S. hyicus, S. intermedius e S. delphini species were identified. Among the cepes of negative coagulase Staphylococcus6, S. gallinarum, S. cloosii, e S. xylosus were predominant. The presence of these microorganisms in milk is a motive to be worried about concerning food safety, for species like S. aureus, S. hyicus e S. intermedius are potential producers of thermostable enterotoxins.

Avaliação da contaminação de ovos comercializados na cidade de São Luís, MA por Salmonella spp / Evaluation of contamination of eggs commercialized in São Luís, MA by Salmonella spp

Um dos maiores desafios deste século continua sendo a produção de alimentos. A questão não é apenas produzir alimentos, mas assegurar a qualidade dos produtos para o consumidor final. Objetivou-se neste trabalho avaliar a contaminação de ovos comercializados na cidade de São Luís/MA por Salmonella spp. Foram analisadas 80 amostras de ovos oriundos de oito diferentes pontos comerciais. Nos resultados das análises microbiológicas foi evidenciado que 100% das amostras possuíam ausência de Salmonella spp., porém, 35% estavam contaminadas por bactérias pertencentes à família Enterobacteriaceae. Apesar de não ter sido constatada a presença de Salmonella spp.nas amostras analisadas, baseando-se nos resultados conclui-se que ocorreram falhas durante o processo de higienização dos ovos comercializados na cidade de São Luís/ MA, sendo necessárias melhorias na manipulação e acondicionamento dos ovos comercializados, visando minimizar potenciais riscos à saúde do consumidor.

One of the largest challenges of this century, it continues to be the production of foods for the population. The question is not just to produce food, but also to assure the products quality for the final consumer. In this context, the quality control of food becomes necessary in the sector nutritional. This work has for goal to evaluate microbiological aspects of the eggs consumed in the city of São Luís/ MA. They were analyzed 80 samples of eggs derived of eight markets different. The results of the analyses microbiological evidenced that 35% of the samples analyzed was contaminated. That result showed that the microbiological quality of the eggs commercialized in some markets city of São Luís/MA, is not in satisfactory terms for the consumption, being, therefore a risk in potential for the consumer health.