ABSTRACT
Cell-penetrating compounds are substances that enhance the cellular uptake of various molecular cargoes that do not easily cross the cellular membrane. The majority of cell-penetrating compounds described in the literature are cell-penetrating peptides (CPPs). This review summarizes the various structural types of cell-penetrating compounds, with the main focus on CPPs. The authors present a brief overview of the history of CPPs, discuss the various types of conjugation of CPPs to biologically active cargoes intended for cell internalization, examine the cell-entry mechanisms of CPPs, and report on the applications of CPPs in research and in preclinical and clinical studies.
Subject(s)
Cell Membrane/metabolism , Cell-Penetrating Peptides/genetics , Cell-Penetrating Peptides/metabolism , Drug Delivery Systems/methods , Amino Acid Sequence , Animals , Cell Membrane/drug effects , Cell-Penetrating Peptides/administration & dosage , Endocytosis/drug effects , Endocytosis/physiology , HumansABSTRACT
Inflammation is a vital defense mechanism of living organisms. However, persistent and chronic inflammation may lead to severe pathological processes and evolve into various chronic inflammatory diseases (CID), e.g. rheumatoid arthritis, multiple sclerosis, multiple sclerosis, systemic lupus erythematosus or inflammatory bowel diseases, or certain types of cancer. Their current treatment usually does not lead to complete remission. The application of nanotherapeutics may significantly improve CID treatment, since their accumulation in inflamed tissues has been described and is referred to as extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS). Among nanotherapeutics, water-soluble polymer-drug conjugates may be highly advantageous in CID treatment due to the possibility of their passive and active targeting to the inflammation site and controlled release of active agents once there. The polymer-drug conjugate consists of a hydrophilic biocompatible polymer backbone along which the drug molecules are covalently attached via a biodegradable linker that enables controlled drug release. Their active targeting or bio-imaging can be achieved by introducing the cell-specific targeting moiety or imaging agents into the polymer conjugate. Here, we review the relationship between polymer conjugates and inflammation, including the benefits of the application of polymer conjugates in inflammation treatment, the anti-inflammatory activity of polymer drug conjugates and potential polymer-promoted inflammation and immunogenicity.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/metabolism , Polymers/administration & dosage , Polymers/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Polymers/chemistry , Treatment OutcomeABSTRACT
We report the detection and isolation of four almost identical strains of West Nile virus (WNV) lineage 2from Culex modestus mosquitoes collected at three fish ponds in South Moravia, Czech Republic, during August 2013. Phylogenetic analysis demonstrated that the Czech WNV strains isolated are closely related to Austrian, Italian and Serbian strains reported in 2008,2011 and 2012, respectively. Our findings show the current northernmost range of lineage 2 WNV in Europe.
Subject(s)
Culex/virology , West Nile virus/genetics , West Nile virus/isolation & purification , Animals , Culicidae/virology , Czech Republic/epidemiology , Endemic Diseases , Europe/epidemiology , Insect Vectors/virology , Italy , Molecular Sequence Data , Phylogeny , Prevalence , RNA, Viral/genetics , RNA, Viral/isolation & purification , West Nile Fever/epidemiology , West Nile virus/classificationABSTRACT
Two strains of Tahyna virus (TAHV; Orthobunyavirus, Bunyaviridae) were isolated from 4,568 (92 pools) female Anopheles hyrcanus Pallas (Diptera, Culicidae) mosquitoes collected on the fishponds in South Moravia (Czechland, central Europe) during July-August 2013. This is the first isolation of TAHV from An. hyrcanus in Europe. An. hyrcanus is a species new to Czechland since 2007; its population density was very high in the year 2013 at these ponds. The virus isolation procedure was based on intracerebral inoculation of newborn mice; moreover, the positive pools were also tested by polymerase chain reaction and found to contain TAHV RNA. An. hyrcanus, feeding preferentially on mammals including humans, may be a new potential vector for TAHV in Europe.
Subject(s)
Anopheles/virology , Encephalitis Virus, California/isolation & purification , Mosquito Vectors/virology , Animals , Czech Republic , Female , MiceABSTRACT
Correlation of 24 different clinical and laboratory measures was performed for a calculation of the prognosis in 65 children with newly diagnosed acute lymphoblastic leukemia (ALL). The hematologic as well as genetic parameters were studied at the time of diagnosis. It was shown that the initial blast count in peripheral blood is the most important risk factor for the prognosis of ALL. Cytogenetic, DNA cytometric, and pedigree data correlate with blast count and also seem to be very important determinants for ALL prognosis. The statistically significant increase in the incidence of neoplasms in ALL families is reported.
