ABSTRACT
Human papillomaviruses of high carcinogenic risk (HR HPVs) are major etiological agents of malignant diseases of the cervix, vulva, penis, anal canal, larynx, head, and neck. Prophylactic vaccination against HPV, which mainly covers girls and women under 25, does not prevent vertical and horizontal HPV transmission in infants and children and does not have a therapeutic effect. As a result, a significant proportion of the population is not protected from the HPV infection and development of HPV-associated neoplastic transformation and cancer, which indicates the need for development and introduction of therapeutic HPV vaccines. Unlike prophylactic vaccines aimed at the formation of virus-neutralizing antibodies, therapeutic vaccines elicit cellular immune response leading to the elimination of infected and malignant cells expressing viral proteins. The ideal targets for vaccine immunotherapy are highly conserved HR HPV oncoproteins E6 and E7 expressed in precancerous and tumor tissues. Here, we describe expression of these proteins during different stages of HPV infection, their antigenic and immunogenic properties, and T-cell epitopes, the response to which correlates with natural regression of HPV-induced neoplastic changes. The review describes patterns of E6 and E7 oncoproteins presentation to the immune system as components of candidate vaccines along with the results of the most promising preclinical trials and animal models used in these trials. Special attention is paid to vaccine candidates which have shown efficacy in clinical trials in patients with HPV-associated neoplastic changes.
Subject(s)
Papillomaviridae/immunology , Papillomavirus Infections/therapy , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/virology , Animals , Bacterial Vaccines/therapeutic use , Cancer Vaccines/therapeutic use , Disease Models, Animal , Female , Humans , Male , Mice , Molecular Targeted Therapy , Papillomavirus E7 Proteins/immunology , Papillomavirus E7 Proteins/metabolism , Papillomavirus Vaccines/economics , Recombinant Proteins/immunology , T-Lymphocytes, Cytotoxic/immunology , Vaccines, DNA/therapeutic useABSTRACT
We studied the role of calcium-regulating structures of slow- (m. soleus, SOL) and fast-twitch (m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са2+ elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca2+ balance.
Subject(s)
Calcium/metabolism , Muscle Fibers, Slow-Twitch/metabolism , Plant Extracts/pharmacology , Transcriptional Activation/drug effects , Animals , Camellia sinensis/chemistry , Drug Evaluation, Preclinical , Male , Metabolic Networks and Pathways , Muscle Fibers, Slow-Twitch/drug effects , Physical Conditioning, Animal , Rats, Wistar , TranscriptomeABSTRACT
Aging is a process that depends on a variety of both external and internal factors. The biological age of a person determines body deterioration and the risk of age-related diseases. Currently, as indicators of biological age are considered different characteristics including average length of telomeres in cells and the level DNA methylation. We propose to combine the two approaches to create a model to assess the biological age of the person. Application of qPCR to determina the length of telomeres and MS-HRM for analysis of DNA methylation will help us to determine the parameters of interest quickly when using a minimum set of equipment.
Subject(s)
Aging/genetics , DNA Methylation , Longevity/genetics , Models, Biological , Telomere Homeostasis/genetics , Telomere/chemistry , Cellular Senescence/genetics , DNA/genetics , DNA/metabolism , Epigenesis, Genetic , Eukaryotic Cells/cytology , Eukaryotic Cells/metabolism , Humans , Nucleic Acid Denaturation , Real-Time Polymerase Chain ReactionABSTRACT
Myocarditis is defined as myocardial inflammation, followed by cardiomyocyte necrosis. Diagnostics of myocarditis is based on unsafe and complicated method of endomyocardial biopsy (EMB). Development of myocarditis might alter gene expression not only in cardiac but in peripheral blood cells (PBC) as well. So, transcription profiles can be considered as possible biomarkers for the given pathology. At the moment, there are no reference genes defined for expression analysis in myocarditis studies. In this study, we analyzed mRNA content of six housekeeping genes in EMB and PBC samples. An algorithm for processing qPCR results obtained under the limited amount of sample is proposed. Set of GAPDH and HPRT1 genes has been selected for normalization of gene expression profiles in cardiac tissue and blood cells under the studies of myocarditis.
