Seroprevalence of mucosal and cutaneous human papillomavirus (HPV) types among children and adolescents in the general population in Germany

Background In Germany, HPV vaccination of adolescent girls was introduced in 2007. Nationally representative data on the distribution of vaccine-relevant HPV types in the pre-vaccination era are, however, only available for the adult population. To obtain data in children and adolescents, we assessed the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1–17 years living in Germany in 2003–2005. Methods Serum samples were tested for antibodies to nine mucosal and seven cutaneous HPV types. The samples had been collected during the nationally representative German Health Interview and Examination Survey for Children and Adolescents in 2003–2006. We calculated age- and gender-specific HPV seroprevalence. We used multivariable regression models to identify associations between demographic and behavioral characteristics and HPV seropositivity. Results We found low but non-zero seroprevalence for the majority of tested HPV types among children and adolescents in Germany. The overall seroprevalence of HPV-16 was 2.6%, with slightly higher values in adolescents. Seroprevalence of all mucosal types but HPV-6 ranged from 0.6% for HPV-33, to 6.4% for HPV-31 and did not differ by gender. We found high overall seroprevalence for HPV-6 with 24.8%. Cutaneous HPV type seroprevalence ranged from 4.0% for HPV-38 to 31.7% for HPV-1. In the majority of cutaneous types, seroprevalence did not differ between boys and girls, but increased sharply with age, (e.g., HPV-1 from 1.5% in 1–3-years-old to 45.1% in 10–11-years-old). Associations between behavioral factors and type-specific HPV prevalence were determined to be heterogeneous. Conclusions We report the first nationally representative data of naturally acquired HPV antibody reactivity in the pre-HPV-vaccination era among children and adolescents living in Germany. These data can be used as baseline estimates for evaluating the impact of the current HPV vaccination strategy targeting 9–14-years-old boys and girls.

CONTRIBUIÇÃO DO SISTEMA CRISPR CAS-9 NOS AVANÇOS DA ONCOLOGIA

Introdução: O câncer é uma das doenças que apresentam maior morbimortalidade, responsável por 9.6 milhões de mortes e 18 milhões de novos casos em 2018, estando entre as quatro principais causas de mortes prematuras (antes dos 70 anos de idade), um em cada cinco mortes no mundo é relacionada a doença. A incidência e a mortalidade têm aumentado e seus principais motivos são o envelhecimento populacional e prevalência dos fatores de risco (predisposição genética, consumo de álcool, tabaco, dieta, sedentarismo e como também o papiloma vírus humano (HPV).(1, 2) De maneira geral, os tumores são resultados de mutações em certos pontos do genoma, principalmente naqueles que estão diretamente relacionados ao mecanismo de reparo do DNA e apoptose celular que ocasiona multiplicação anormal de algum tipo de célula, podendo ocorrer migração para outras partes do corpo, se desenvolvendo fora do local de origem (metástase).(3) Objetivos: descrever a contribuição do sistema Crispr Cas-9 nos avanços da oncologia. Métodos: Trata-se de um estudo de literatura que consultou a base de dados Us National Library of Medicine National Institutes of Health (Pubmed) de 2016 até 2021. Resultados: A pesquisa realizada por Williams e Largaespada fez uso do sistema CRISPR CAS-9 (Clustered Regularly Interspaced Short Palindromic Repeats) para a ampliação dos tratamentos da neurofibromatose causada por mutações no gene supressor de tumor NF1 (codifica a neurofibromina).(4) Já Xiao, Chen e Cui lançaram mão da CRISPR CAS-9 para a depleção do mRNA-21 em carcinoma nasofaringe tendo êxito em suprimir o crescimento celular, bem como sua proliferação nas células CNE2. Ao comparar com grupo controle com o grupo experimental (sgRNA-mir-21) notou-se que expressões de Bcl-2 e Bcl-L diminuíram e a Caspase-3 foi ativada e esses resultados implicaram que o knockdown direcionado do miR-21 foram capazes de induzir apoptose nas células alvos.(5) Conclusões: Levando-se em consideração o que foi abordado, fica evidente que apesar do câncer ser uma doença multifatorial, o novo mosaico que a biotecnologia emergente CRSPR CAS-9 proporciona é um grande diferencial já que pode levar a conhecer as doenças por pontos que antes não eram possíveis e como também transformar o modo de combate-las.

Identification of Immunodominant T-lymphocyte Epitope Peptides in HPV 1, 2 and 3 L1 Protein for Novel Cutaneous Wart Vaccine

Background: Common warts and flat warts are caused by the human papillomavirus (HPV). Peak incidence of wart infection occurs in schoolchildren aged 12-16, where prevalence can be as high as 20%. Traditional treatments aimed at destruction of wart tissue have low clearance rates and high recurrence rates. Occasional reports have even shown warts becoming malignant and progressing into verrucous carcinoma. Current licensed HPV vaccines largely target higher-risk oncogenic HPV types, but do not provide coverage of low-risk types associated with warts. To date, little attention has been given to the development of effective, anti-viral wart treatments. Objective: This study aims to identify immunodominant T-lymphocyte epitopes from the L1 major capsid protein of HPV 1, 2 and 3, a foundational step in bioengineering a peptide-based vaccine for warts. Methods: Cytotoxic T-cell and helper T-cell epitopes were predicted using an array of immunoinformatic tools against a reference panel of frequently observed MHC-I and MHC-II alleles. Predicted peptides were ranked based on IC50 and IFN-γ Inducer Scores, respectively, and top performing epitopes were synthesized and subjected to in vitro screening by IFN-γ enzyme-linked immunosorbent spot assay (ELISpot). Independent trials were conducted using PBMCs of healthy volunteers. Final chosen peptides were fused with flexible GS linkers in silico to design a novel polypeptide vaccine. Results: Seven immunodominant peptides screened from 44 predicted peptides were included in the vaccine design, selected to elicit specific immune responses across MHC class I and class II, and across HPV types. Evaluation of the vaccine′s properties suggest that the vaccine is stable, non-allergenic, and provides near complete global population coverage (>99%). Solubility prediction and rare codon analysis indicate that the DNA sequence encoding the vaccine is suitable for high level expression in Escherichia coli. Conclusions: In sum, this study demonstrates the potential and lays the framework for the development of a peptide-based vaccine against warts.

Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach

Herpes Simplex Virus (HSV) is an infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV viruses, HSV-1 and HSV-2, are the most dangerous HSV viruses. Every year, millions of people get infected with this menacing virus, however, no satisfactory treatment or vaccine has not yet been discovered to fight against HSV. Although there are some anti-viral therapies, however, studies have showed that such anti-viral therapies may also fail to provide good impact. In this study, a possible subunit vaccine against HSV-1, strain-17, was designed using the tools and reverse vaccinology and bioinformatics. Three potential antigenic envelope glycoproteins were selected from nine envelope glycoproteins, for possible vaccine construction. Potential epitopes capable of inducing high immunogenic response and at the same time have non-allergenicity and conservancy across other strains and species, were selected by some robust analysis, for vaccine construction. Finally, three possible vaccines were designed. Each of the vaccine construct differ from each other only in their adjuvant sequences and based on molecular docking analysis, one best vaccine construct was selected for molecular dynamics simulation study and in silico codon adaptation. The experiment showed that the selected best vaccine should be good candidate against HPV-1, strain-17. However, wet lab study should be conducted on the suggested vaccine(s) for confirming their potentiality, safety and efficacy.

Deteksi Dini Oral Squamous Sel Carcinoma (OSCC) dengan Menggunakan Human Papillomavirus (HPV) sebagai Penandanya

Insidensi oral squamous cell carcinoma (OSCC) secara global diprediksi akan meningkat sekitar 62% pada tahun 2035. Salah satu pathogen yang dapat menyebabkan keganasan adalah human papillomavirus (HPV). Pada kasus OSCC sekitar 17% hingga 87% diakibatkan oleh infeksi HPV.1–3 OSCC memiliki prognosis yang baik jika terdeteksi pada tahap dini. Deteksi HPV pada OSCC menjadi biomarker penting, dan dapat digunakan sebagai screening populasi memiliki resiko terkena OSCC.

Quantitative Analysis on the role ofRaffinose Synthasein Hippocampal Neurons

1AbstractA diminished level of endogenous antioxidant in cells/tissues is associated with reduced resistance to oxidative stress. Raffinose synthase (RFS), a protective molecule regulates gene expression/function by controlling reactive oxygen species (ROS) levels, which has shown to be involved in a number of degenerative diseases. We confirmed the ubiquitous expression of this antioxidant protein in both human hippocampal neuron (HNN) and mouse hippocampal (HHPC-43) cell lines by an immunoblot and reverse transcriptase PCR (RT-PCR). Using a construct of RFS protein linked to CXCR-4, the transduction domain from HPV-1 CXCR-4 protein, we showed that RFS was transduced into both HNN, as well as HHPC-43 by the means of a western blot analysis. Further we proved that the protein was biologically active, and was shown to actively reduce the oxidative stress produced byparaquatand serum depletion in both human and mouse neuronal cell lines, increasing the viability of the cells. The results suggest that the intracellular delivery of RFS using CXCR-4 can be used to lower increased levels of ROS inside the cells and hence can be further investigated as a therapeutic tool in various ROS related neurodegenerative disorders.

Cutaneous Human Papillomavirus E7 Type-Specific Effects on Differentiation and Proliferation of Organotypic Skin Cultures

Background: A role for cutaneous human β-papillomavirus (HPV) types as co-factors in the development of non-melanoma skin cancer has been postulated. Here we have investigated the effects of E7 expression on keratinocyte differentiation, proliferation and cell-cycle proteins in organotypic skin cultures.Methods: Recombinant retroviruses containing the E7 genes from cutaneous HPV types 1, 4, 5, 8, 20, 38 and RTRX7 were produced that include types associated with benign and malignant lesions. Adult human primary keratinocytes were transduced with these recombinant retroviruses and differentiated into skin-equivalents using de-epidermalised human dermis.Results: Expression patterns of the basal keratinocyte marker cytokeratin 14 (CK14) were not altered by any of the viral E7 types analysed. However, expression of the early and late differentiation markers CK10 and involucrin were markedly altered in HPV 1, 4 and 38 cultures. The highest proliferation rates in basal cell layers, as judged by BrdU and Ki67 staining, were observed in HPV 1, 4 and 38 cultures. Interestingly, co-expression of cyclin E and p16INK4a within the same cell of the suprabasal cell layers was observed only in cultures generated using E7 of HPV 5 or HPV 8.Conclusion: HPV types associated with either benign or malignant lesions perturb keratinocyte proliferation and differentiation in different ways. Moreover, expression of E7 from HPV 5 or HPV 8 seem able to overcome p16INK4a induced cell cycle arrest in a subset of keratinocytes.

Analysis of Explosion Combustion Phenomenon with Ammonium Nitrate

In this study, an explosion combustion phenomenon of ammonium nitrate (ρ=1.7kg/cm3) was used instead of the explosive PETN and the ultra-high-speed destruction phenomenon of aluminum cylinder was analyzed. The mix powder obtained by mixing aluminum powder (ρ=2.7kg/cm3) and ammonium nitrate was used instead of the explosive PETN, and an explosive combustion phenomenon was generated using copper wire explosion by high-voltage capacitor bank (40kV, 12.5 /F). Ammonium nitrate and aluminum powder are kneaded in a combination ratio of 5 : 1 in mass. An aluminum cylinder was destroyed by the phenomenon. The experiments were conducted using various diameters of ammonium nitrate particle and the photographs of the phenomenon were taken by the high-speed camera (IMACON468) and the high-speed video camera (HPV-1). The fragments of aluminum cylinder were collected and their dimensions were measured. The explosion phenomenon and fragments were compared with the result by explosive PETN. This paper presents these experiments and analysis result. And, hydro codes have been applied to simulate the deformation behavior of the aluminum cylinder.

Design and Experiment of Compact Projectile Accelerator Driven by Explosives

This paper presents the design of a compact size projectile accelerator, and its application. To meet the various needs such as a compact body size to use under various experimental conditions, an easy maintenance for repetitive experiments during a certain period, and a capability of the velocity control, the compact accelerators were newly designed with a direct explosive drive method. Two different types of accelerator were designed: a PMMA accelerator and a metal accelerator. The pictures of the projectile shoot using the designed accelerators were recorded by SHIMADZU HyperVision HPV-1 high-speed video camera. As a result, it was recognized that the PMMA accelerator was failed to accelerate the projectile, while the metal accelerator succeeded to accelerate it effectively. The accelerating performance of the metal accelerator was further investigated. The explosives for projectile acceleration were Emulsion explosive and Composition C4 explosive weighing 5 to 35g. It was found that the metal accelerator has the capability to control the projectile velocity adjusting the weight of the explosives, and there is an approximate linear correlation between them in our experimental range. A series of impact tests on 5052S aluminum alloy targets was examined using the accelerator.