Search results for "protein"
showing 10 items of 21431 documents
Oxidatively generated base modifications in DNA: Not only carcinogenic risk factor but also regulatory mark?
2016
The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively. More recently, considerable evidence has been obtained that also 8-oxo-7,8-dihydroguanine (8-oxoG), a frequent pro-mu…
Das Usher-Syndrom, eine Ziliopathie des Menschen
2018
ZusammenfassungDas humane Usher-Syndrom (USH) ist eine seltene, komplexe genetische Erkrankung, die sich in kombinierter Taubblindheit manifestiert. Aufgrund der Ausprägung des Krankheitsbilds werden 3 klinische Typen (USH1 – 3) unterschieden. Für eine korrekte Diagnose sind zusätzlich zu den auditorischen Tests im Zuge des Neugeborenenscreens auch frühe ophthalmologische Untersuchungen und eine molekulargenetische Abklärung notwendig. Die bislang 10 bekannten USH-Gene codieren für heterogene Proteine, die in Proteinnetzwerken miteinander in Funktionseinheiten kooperieren. Im Auge und im Ohr werden USH-Proteine vor allem in den mechanosensitiven Haarsinneszellen und den Stäbchen- und Zapfen…
MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma
2020
Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferatio…
Sensitivity and Specificity of Human Papillomavirus (HPV) 16 Early Antigen Serology for HPV-Driven Oropharyngeal Cancer: A Systematic Literature Revi…
2021
Simple Summary Serum antibodies against human papillomavirus 16 (HPV16) proteins are associated with HPV-driven oropharyngeal cancer (HPV-OPC). The HPV status of OPC cases is clinically relevant because patients with HPV-OPC show improved survival and treatment response compared to tobacco- or alcohol-induced OPC. In clinical settings, molecular HPV tumor status is usually determined by tissue-based methods detecting molecular markers, such as viral nucleic acids or p16 overexpression. Antibodies against HPV16 in peripheral blood were shown to be very accurate in determining the molecular HPV tumor status in multiple studies. In this work, we reviewed and summarized the available literature…
Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice.
2017
It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been proposed as a new pharmacological treatment for psychostimulant addiction. In the present study, we intend to evaluate whether the blockade of the NO synthesis (NOS) interferes with the rewarding effects of MDMA in the conditioned preference place (CPP) paradigm in young adult male mice. Our results indicated that mice treated with 7-nitroindazole (…
Protein-bound tyrosine oxidation, nitration and chlorination by-products assessed by ultraperformance liquid chromatography coupled to tandem mass sp…
2015
Abstract Background Free radicals cause alterations in cellular protein structure and function. Oxidized, nitrated, and chlorinated modifications of aromatic amino acids including phenylalanine and tyrosine are reliable biomarkers of oxidative stress and inflammation in clinical conditions. Objective To develop, validate and apply a rapid method for the quantification of known hallmarks of tyrosine oxidation, nitration and chlorination in plasma and tissue proteins providing a snapshot of the oxidative stress and inflammatory status of the organism and of target organs respectively. Material and Methods The extraction and clean up procedure entailed protein precipitation, followed by protei…
Cardiac regenerative capacity is age- and disease-dependent in childhood heart disease
2018
Objective We sought to define the intrinsic stem cell capacity in pediatric heart lesions, and the effects of diagnosis and of age, in order to inform evidence-based use of potential autologous stem cell sources for regenerative medicine therapy. Methods Ventricular explants derived from patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TF), dilated cardiomyopathy (DCM) and ventricular septal defect (VSD) were analyzed following standard in vitro culture conditions, which yielded cardiospheres (C-spheres), indicative of endogenous stem cell capacity. C-sphere counts generated per 5 mm3 tissue explant and the presence of cardiac progenitor cells were correlated to pa…
Genetic characterization of influenza viruses from influenza-related hospital admissions in the St. Petersburg and Valencia sites of the Global Influ…
2016
Abstract Background Continuous surveillance for genetic changes in circulating influenza viruses is needed to guide influenza prevention and control. Objectives To compare intra-seasonal influenza genetic diversity of hemagglutinin in influenza A strains isolated from influenza hospital admissions collected at two distinct sites during the same season. Study design Comparative phylogenetic analysis of full-length hemagglutinin genes from 77 isolated influenza A viruses from the St. Petersburg, Russian Federation and Valencia, Spain sites of the Global Influenza Hospital Surveillance Network (GIHSN) during the 2013/14 season. Results We found significant variability in A(H3N2) and A(H1N1)pdm…
In silico identification of small molecules as new cdc25 inhibitors through the correlation between chemosensitivity and protein expression pattern
2021
The cell division cycle 25 (Cdc25) protein family plays a crucial role in controlling cell proliferation, making it an excellent target for cancer therapy. In this work, a set of small molecules were identified as Cdc25 modulators by applying a mixed ligand-structure-based approach and taking advantage of the correlation between the chemosensitivity of selected structures and the protein expression pattern of the proposed target. In the first step of the in silico protocol, a set of molecules acting as Cdc25 inhibitors were identified through a new ligand-based protocol and the evaluation of a large database of molecular structures. Subsequently, induced-fit docking (IFD) studies allowed us…
Hepatitis B Virus Subverts the Autophagy Elongation Complex Atg5-12/16L1 and Does Not Require Atg8/LC3 Lipidation for Viral Maturation
2018
ABSTRACT Previous studies indicated that hepatitis B virus (HBV) stimulates autophagy to favor its production. To understand how HBV co-opts autophagy as a proviral machinery, we studied the roles of key autophagy proteins in HBV-replicating liver cell cultures. RNA interference-mediated silencing of Atg5, Atg12, and Atg16L1, which promote autophagophore expansion and LC3 membrane conjugation, interfered with viral core/nucleocapsid (NC) formation/stability and strongly diminished virus yields. Concomitantly, the core/NC membrane association and their sorting to envelope-positive compartments were perturbed. A close inspection of the HBV/autophagy cross talk revealed that the virus depended…