Envolvimento da imunidade inata na infecção do Papilomavírus Humano

Innate immunity is the first defense in the host and is crucial to prevent Human Papillomavirus (HPV) infection and subse - quent development to neoplasia. HPV is involved in the squamous intraepithelial lesions and cervical cancer development. Fortunately, not everyone infected with HPV develop cervical cancer as the immune system can control the virus infection. Innate immunity is the first defense in the host and is crucial to prevent HPV infection and subsequent development to neoplasia. This type of immunity has different antiviral defense pathways, among which are: physical barriers (skin and mucous membranes), keratinocytes and immune cells such as Langerhans cells, dendritic cells, and natural killer cells, which may secrete interferons and cytokines that activate signaling cascades that may prevent HPV infection. However, HPV has also developed various strategies to evade this immune response, which could allow the squamous intraepithelial lesions and cervical cancer development. The aim of this review was to describe the innate immunity involvement in HPV infection

Chemical composition, physicochemical evaluation and sensory analysis of yogurt added with extract of polyphenolic compounds from Quercus crassifolia oak bark

Introduction: A diet high in calories and saturated fats has been associated with health problems that have been increasing worldwide. Therefore, it is required to increase the number of formulated foods that generate well-being to health. Yogurt is a widely consumed food by all sectors of the population and it can be used as a vehicle to incorporate bioactive compounds. The phenolic compounds present in forest residues, such as those from oak bark, can be used and incorporated into yogurt, to increase its benefits as a functional food. Objective: The objective of this study was to develop a multifunctional yogurt enriched with vegetable oil (2.3% w/w) as a source of omega 6 and 3 and adding nanocapsules (24.5% w/w) of an extract of oak bark from Quercus crassifolia, rich in in phenolic compounds and high antioxidant capacity. Methods: Three yogurt formulations were prepared: F1: yogurt was made with non-fat milk, used as a control, F2: yogurt was prepared with non-fat milk and added with vegetable palm oil, and F3: non-fat yogurt was added with vegetable oil and nanoencapsulated oak bark phenolic extract. The yogurts were characterized in their chemical composition, microbiological analysis, and sensory analysis. Results: The multifunctional product F3 and product F2 presented lactic acid bacteria in concentration of 3.01X106 and 4.73x106, respectively, preserving characteristics of probiotic food. Product F3 presented low levels of syneresis (7.34%) and it was significantly different from the control yogurt (9.01%). The viscosity increased from 150 cP in the control yogurt to 341 cP in F3, due to the increase in the concentrations of solids by nanoencapsulating the phenolic. The wall material used for nanoencapsulation was sodium caseinate and mantodextrin. However, this increase in viscosity did not affect the sensory evaluation of the product. There were no significant differences between the control yogurt and the F2 and F3 products. Conclusion: A yogurt added with vegetable oil and nanoencapsulated oak bark phenolic extract was obtained. It was enhanced by the presence of probiotics, bioactive compounds, and essential fatty acids, and then evaluated and accepted by a sensory panel. Nanoencapsulation is a viable alternative to mask the characteristic astringent taste of phenolic compounds because it was not detected by the panelists

Genotyping of Human Papillomavirus in cervical Squamous Intraepitelial Lesions in Méxica Women

Approximately 40 genotypes of the human papillomavirus (HPV) have been identified in cervical mucosa. In particular, HPV-16 and HPV-18 have been associated with cervical neoplasia. Squamous intraepithelial lesions (SILs) are precursors of cervical cancer. This study aimed to identify the HPV by genotype in SILs using a line ar array genotyping test in a population in the State of México. We performed a cross-sectional study of 129 patients (women of the State of México) who completed a risk factor questionnaire and were diagnosed as being with or without SIL by colposcopy. We obtained cervical swab samples from these patients and genotyped them using a Linear Array HPV Genotyping assay from ROCHE®. Forty-nine (37.98%) samples were positive for the HPV, and 24 genotypes were found among these samples. The most common genotype was HPV-16. The 12 genotypes found in both high- and low-grade SILs were HPV-6, 16, 31, 39, 51, 52, 53, 58, 59, 61, 67, and 84, 7 of which were high risk: HPV-16, 31, 39, 51, 52, 58, and 59. In the population studied, the most frequent genotype was HPV-16, multiple infections were found, and four patients without injury tested positive for the HPV

Sensibilidad y especificidad de las pruebas de citología, colposcopia, biopsia y detección del virus del papiloma humano en lesión intraepitelial escamosa

La citología, colposcopia y biopsia son pruebas de rutina en el diagnóstico del cáncer cervicouterino (CaCu); en un gran número de estudios se ha asociado el virus del papiloma humano (vph) con el desarrollo de lesiones cancerosas y precancerosas. En consecuencia, es importante determinar si la prueba de tipificación del adn, junto con las primeras, incrementa la probabilidad de diagnóstico oportuno en casos de lesión intraepitelial escamosa de alto grado (lie-ag). Para tal efecto, se llevó a cabo un estudio transversal con 38 pacientes. La tipificación del vph se realizó por el método de Linear Array y se consultaron los expedientes para obtener los resultados de citología, colposcopia y biopsia; se calcularon los valores de sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo, coeficiente de verosimilitud, probabilidad pre-test y probabilidad post-test, mediante metodologías descritas en estudios previos. Para el diagnóstico de lie-ag, al incluir la prueba de tipificación del adn, la sensibilidad está arriba de 80% y la especificidad es menor a 42%. La probabilidad de encontrar un paciente con lie-ag cuando se usa la citología junto con la tipificación de Linear Array tiene un incremento de 7%; en la colposcopia y Linear Array aumentó 10% y en la biopsia y Linear Array, 3%. En conclusión, en la prueba de tipificación se incrementa la posibilidad post-test de detectar al paciente con lie-ag

Expresión de interferón gamma en la infección por el virus del papiloma humano y por Chlamydia trachomatis en muestras cervicales.

infecciónpor VPH y por Chlamydia trachomatis en pacientes con lesión intraepitelial escamosa.Método: Se incluyeron 100 muestras de pacientes diagnosticadas por colposcopía, con y sin lesiónintraepitelial escamosa, en quienes se efectuó el diagnóstico de infección por VPH y/o C. trachomatis. Se cuantificó la expresión relativa de interferón gamma con la prueba de transcriptasa reversa-PCR entiempo real (RT-PCR).Resultados: Las unidades relativas de la expresión de interferón gamma fueron de 13, 1,8 y 0,3 en lacoinfección por VPH y C. trachomatis, en la infección por VPH y en la infección por C. trachomatis, respec-tivamente.Conclusión: La infección por VPH y por C. trachomatis puede constituir un factor estimulante de la expre-sión de interferón gamma.Este trabajo fue financiado por la Secretaría de Investigación y Estudios Avanzados Universidad Autónoma del Estado de México (número de proyecto 3097)

Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status.

INTRODUCTION:Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor-positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk. METHODS:We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status. RESULTS:We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. CONCLUSIONS:Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors

Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis

Systemic Mastocytosis (SM) is a clonal disease characterized by abnormal accumulation of mast cells in multiple organs. Clinical presentations of the disease vary widely from indolent to aggressive forms, and to the exceedingly rare mast cell leukemia. Current treatment of aggressive SM and mast cell leukemia is unsatisfactory. An imatinib-resistant activating mutation of the receptor tyrosine kinase KIT (KIT D816V) is most frequently present in transformed mast cells and is associated with all clinical forms of the disease. Thus the etiology of the variable clinical aggressiveness of abnormal mast cells in SM is unclear. TET2 appears to be mutated in primary human samples in aggressive types of SM, suggesting a possible role in disease modification. In this report, we demonstrate the cooperation between KIT D816V and loss of function of TET2 in mast cell transformation and demonstrate a more aggressive phenotype in a murine model of SM when both mutations are present in progenitor cells. We exploit these findings to validate a combination treatment strategy targeting the epigenetic deregulation caused by loss of TET2 and the constitutively active KIT receptor for the treatment of patients with aggressive SM

Sensitization Prevalence, Antibody Cross-Reactivity and Immunogenic Peptide Profile of Api g 2, the Non-Specific Lipid Transfer Protein 1 of Celery

Background: Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. Methodology: 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. Results: IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Conclusions: Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.Christian-Doppler Research Association, Biomay AG, Vienna, AustriaItalian Ministry of Healt

Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status

INTRODUCTION: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor–positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk. METHODS: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status. RESULTS: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. CONCLUSIONS: Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors