This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like 211At, 223Ra, 225Ac/213Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging. Special attention is given to the nuclear recoil effect and its impacts on the possible use of alpha emitters for cancer treatment, proper dose estimation, and labelling chemistry. The most recent and important achievements in the development of alpha emitters carrying vectors for preclinical and clinical use are highlighted along with an outlook for future developments.

• MeSH
• Actinium chemistry   therapeutic use   MeSH
• Alpha Particles therapeutic use   MeSH
• Astatine chemistry   therapeutic use   MeSH
• Bismuth chemistry   therapeutic use   MeSH
• Chelating Agents chemistry   pharmacokinetics   MeSH
• Radiation Dosage MeSH
• Heterocyclic Compounds, 1-Ring chemistry   pharmacokinetics   MeSH
• Heterocyclic Compounds chemistry   pharmacokinetics   MeSH
• Small Molecule Libraries chemistry   pharmacokinetics   MeSH
• Humans MeSH
• Neoplasms pathology   radiotherapy   MeSH
• Drug Carriers administration & dosage   chemistry   MeSH
• Radiopharmaceuticals chemistry   therapeutic use   MeSH
• Radioisotopes chemistry   therapeutic use   MeSH
• Radium chemistry   therapeutic use   MeSH
• Dose-Response Relationship, Radiation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• MeSH
• Alpha Particles MeSH
• Particle Accelerators MeSH
• Electrons MeSH
• Nuclear Energy MeSH
• Protons MeSH

Targeted alpha therapy with radionuclides undergoing multiple alpha-particle decays is a promising method of nuclear medicine. To study the effectiveness of alpha versus beta emitters, survival of DU145 prostate cancer cells exposed to 223Ra or 177Lu was assessed. Per decay, the cells were much more sensitive to the alpha than beta emitter. However, per unit dose the sensitivities would be comparable, contrary to the well-known evidence, if the decay energy were deposited within the sample completely and homogeneously. Measurements by Timepix detectors showed about three times higher counts of alpha particles above than below the sample. After the first alpha decay of 223Ra to 219Rn, this gas likely moves upwards and its subsequent three alpha decays occur in the upper part of the sample. Correct estimation of absorbed dose is a critical issue when analysing in vitro data and when translating their results to clinical applications.

• MeSH
• Alpha Particles therapeutic use   MeSH
• Humans MeSH
• Radiometry methods   MeSH
• Radioisotopes therapeutic use   MeSH
• Radium * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Hepatitis C epidemiology   therapy   diagnosis   MeSH
• Interferon-alpha therapeutic use   MeSH
• Hepatitis B virus MeSH
• Publication type
• Collected Work MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• gastroenterologie
• infekční lékařství

• MeSH
• Biological Transport MeSH
• Brefeldin A pharmacology   MeSH
• COP-Coated Vesicles physiology   MeSH
• Polyomavirus physiology   MeSH
• Carrier Proteins analysis   MeSH
• Virion physiology   MeSH
• Virosomes analysis   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

The importance of fluorescence light microscopy for understanding cellular and sub-cellular structures and functions is undeniable. However, the resolution is limited by light diffraction (~200-250 nm laterally, ~500-700 nm axially). Meanwhile, super-resolution microscopy, such as structured illumination microscopy (SIM), is being applied more and more to overcome this restriction. Instead, super-resolution by stimulated emission depletion (STED) microscopy achieving a resolution of ~50 nm laterally and ~130 nm axially has not yet frequently been applied in plant cell research due to the required specific sample preparation and stable dye staining. Single-molecule localization microscopy (SMLM) including photoactivated localization microscopy (PALM) has not yet been widely used, although this nanoscopic technique allows even the detection of single molecules. In this study, we compared protein imaging within metaphase chromosomes of barley via conventional wide-field and confocal microscopy, and the sub-diffraction methods SIM, STED, and SMLM. The chromosomes were labeled by DAPI (4',6-diamidino-2-phenylindol), a DNA-specific dye, and with antibodies against topoisomerase IIα (Topo II), a protein important for correct chromatin condensation. Compared to the diffraction-limited methods, the combination of the three different super-resolution imaging techniques delivered tremendous additional insights into the plant chromosome architecture through the achieved increased resolution.

• MeSH
• Chromosomes, Plant chemistry   genetics   metabolism   MeSH
• DNA Topoisomerases, Type II metabolism   MeSH
• Fluorescent Dyes chemistry   MeSH
• Microscopy, Fluorescence methods   MeSH
• Indoles chemistry   MeSH
• Hordeum cytology   genetics   MeSH
• Microscopy, Confocal methods   MeSH
• Metaphase genetics   MeSH
• Reproducibility of Results MeSH
• Single Molecule Imaging methods   MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

• MeSH
• Adult MeSH
• Hepatitis B blood   pathology   therapy   MeSH
• Interferon-alpha therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Hepatitis B virus genetics   drug effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Optimalizace terapie interferonem alfa ("tailoring"terapie) u chronických hepatitid B a C pomocí monitorování virémie a stanovení sérotypu viru hepatitidy C.; Optimalization of interferon alpha therapy ("tailoring"therapy) in patients with chronic hepatitis B and C using monitoring viremia and detection of hepatitis C virus serotype.

• MeSH
• Hepatitis B, Chronic drug therapy   MeSH
• Hepatitis C, Chronic drug therapy   MeSH
• Interferon-alpha therapeutic use   MeSH
• Ribavirin therapeutic use   MeSH
• Hepatitis B virus drug effects   drug effects   MeSH
• Treatment Outcome MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• virologie
• infekční lékařství
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

Bacteriophages are ubiquitous in nature and represent a vast repository of genetic diversity, which is driven by the endless coevolution cycle with a diversified group of bacterial hosts. Studying phage-host interactions is important to gain novel insights into their dynamic adaptation. In this study, we isolated 12 phages infecting species of the Acinetobacter baumannii-Acinetobacter calcoaceticus complex which exhibited a narrow host range and similar morphological features (podoviruses with short tails of 9-12 nm and isometric heads of 50-60 nm). Notably, the alignment of the newly sequenced phage genomes (40-41 kb of DNA length) and all Acinetobacter podoviruses deposited in Genbank has shown high synteny, regardless of the date and source of isolation that spans from America to Europe and Asia. Interestingly, the C-terminal pectate lyase domain of these phage tail fibres is often the only difference found among these viral genomes, demonstrating a very specific genomic variation during the course of their evolution. We proved that the pectate lyase domain is responsible for phage depolymerase activity and binding to specific Acinetobacter bacterial capsules. We discuss how this mechanism of phage-host co-evolution impacts the tail specificity apparatus of Acinetobacter podoviruses.

• MeSH
• Acinetobacter baumannii virology   MeSH
• Acinetobacter calcoaceticus virology   MeSH
• Genome, Viral genetics   MeSH
• Host Specificity physiology   MeSH
• Podoviridae classification   genetics   metabolism   MeSH
• Polygalacturonase metabolism   MeSH
• Polysaccharide-Lyases metabolism   MeSH
• Protein Domains physiology   MeSH
• Base Sequence MeSH
• Virion genetics   MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Asia MeSH
• Europe MeSH

• MeSH
• DNA, Viral analysis   MeSH
• Adult MeSH
• Interferon-alpha therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Hepatitis, Viral, Human drug therapy   blood   MeSH
• Hepatitis B virus isolation & purification   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH