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Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although −AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than −AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.

Protoporphyrin IX (PpIX) enhances the generation of reactive oxygen species in cells following physicochemical interactions with X-rays. To evaluate the use of porphyrins as radio-sensitizers in radiotherapy, the transcriptomic effects of PpIX and/or X-ray irradiation were investigated in HeLa cells. Microarray experiments were performed using Agilent-014,850 Whole Human Genome Microarray 4x44K G4112F (GEO#: GSE61805). We selected the condition corresponding to 1 μg/mL PpIX exposure prior to 3 Gy-irradiation of cells, and collected cells 24 h post irradiation. X-ray exposure at a dose of 3 Gy did not affect cell survival 24 h post irradiation, regardless of the concentration of PpIX. Approximately 50% cells exposed to X-ray irradiation alone (XT) and 70% cells exposed to PpIX treatment for 6 h before X-ray irradiation (PpIX-XT) lost clonogenic ability. Based on p-values (p < 0.01), we selected genes for functional analysis. The majority of the regulated genes in the XT and PpIX-XT groups were related to cell cycle arrest. Furthermore, transcriptome analysis of the cells collected 24 h post irradiation revealed the fate of the cells that lost clonogenic ability due to cell cycle arrest.

Quasi-One and quasi-two dimensional organic conductors consisting of TTF derivatives such as BEDT-TTF (bis-(ethylene-dithio)-tetra-thia-fulvalene) and TMTCF (C = S; TMTTF: tetra-methyl-tetra-thia-fulvalene, C = Se; TMTSF: tetra-methyl-tetra-selena-fulvalene) have been well investigated in condensed matter physics because of interest in the emerging electric and magnetic properties, such as the spin density wave, charge order, superconductivity, anti-ferromagnetism, and so on. To probe the electronic state, nuclear magnetic resonance (NMR) is one of the most powerful tools as the microscopic magnetometer. A number of 13C-NMR studies have been performed of the double-site central 13C=13C bond substituted molecules. However, problems with the coupled spin system of 13C=13C complicated the interpretation for observations on NMR. Therefore, single-site 13C-enriched molecules are desired. We summarize the problem of Pake doublet and the preparation of the single-site 13C-susbstituted BEDT-TTF and TMTCF molecules. We also demonstrate the superiority of 13C-NMR of the single-site 13C-susbstituted molecule utilizing the hyperfine coupling tensor.

Miniature pigs are useful model animals for humans because they have similar anatomy and digestive physiology to humans and are easy to breed and handle. In this study, whole blood microarray analyses were conducted to evaluate variations of correlation among individuals and ages using specific pathogen-free (SPF) Clawn miniature pigs. Whole blood RNA is easy to handle compared to isolated white blood cell RNA and can be used for health and disease monitoring and animal control. In addition, whole blood is a heterogeneous mixture of subpopulation cells. Once a great change occurs in composition and expressing condition of subpopulations, their associated change will be reflected on whole blood RNA. From 12 to 30 weeks of age, fractions of lymphocytes, monocytes, neutrophils, eosinophils, and basophils in white blood cells showed insignificant differences with age as a result of ANOVA analysis. This study attempted to identify characteristics of age-related gene expression by taking into account the change in the number of expressed genes by age and similarities of gene expression intensity between individuals. As a result, the number of expressed genes was less in fetal stage and infancy period but increased with age, reaching a steady state of gene expression after 20 weeks of age. Variation in gene expression intensity within the same age was great in fetal stage and infancy period, but converged with age. The variation between 20 and 30 weeks of age was comparable to that among 30 weeks individuals. These results indicate that uniformity of laboratory animals is expected for miniature pigs after 20 weeks of age. Furthermore, a possibility was shown that whole blood RNA analysis is applicable to evaluation of physiological state.

BACKGROUND: Currently, no standardized method for measuring intrahepatic fat density via conventional computed tomography (CT) exists. OBJECTIVE: We aim to quantify intrahepatic fat density via material decomposition analysis using rapid kilovolt peak-switching dual-energy (RSDE) CT. METHODS: Homogenized porcine liver and fat (lard) were mixed in various ratios to produce phantoms for fat density verification. The actual fat density was measured on the basis of the phantom volume and weight, and these measurements were used as reference densities. The fat and liver mass attenuation coefficients, which were used as the material basis pairs, were employed in the material decomposition analysis. Then, the measured fat density of each phantom was compared with the reference densities. RESULTS: For fat content differences exceeding 2%, the measured fat density for the phantoms became statistically significant (p < 0.01). The correlation between the reference densities and RSDE-measured fat densities was reasonably high (R > 0.9997); this indicates the validity of this analysis method. CONCLUSIONS: Intrahepatic fat density can be measured using the mass attenuation coefficients of fat and liver in a material decomposition analysis. Given the knowledge of the accuracy and the limitations found in this study, our method can quantitatively evaluate fat density. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transmission and tomographic X-ray measurements are useful in assessing bone structures, but only a few studies have examined cartilage growth because of the poor contrast in conventional X-ray imaging. OBJECTIVE: In this study, we attempted to use the linear attenuation coefficient (LAC) as a metric of tissue-engineered cartilage development, which would be useful in high-throughput screening of cartilage products. METHODS: Assuming that the LAC is related to the amount of extracellular matrix (ECM) in terms of the density and its atomic components, we measured X-ray absorption through tissue-engineered cartilage constructs. Characteristic X-ray beams from a molybdenum microfocus X-ray tube were employed to avoid beam hardening. The correlation of the LAC with mechanical properties was analyzed for verification. RESULTS: The LAC was higher for chondrocyte constructs and lower for fibroblast-dominant constructs and was consistent with the quantification of toluidine blue staining, which is a proof of ECM production. The LAC was positively correlated with the bending modulus but negatively correlated with the dynamic elastic modulus and stiffness, possibly because of the remaining scaffold. CONCLUSIONS: The LAC has the potential to be used as a metric of development of tissue-engineered cartilage. However, the calcified regions should be excluded from analysis to avoid decreasing the correlation between the LAC and the amount of ECM. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (ALA) is a precursor of the photosensitizer used in photodynamic therapy. It accumulates in tumor cells and subsequently metabolizes to protoporphyrin IX (PpIX), which generates singlet oxygen after light irradiation. PpIX enhances the generation of reactive oxygen species following physicochemical interactions with X-rays. ALA-based treatment using fractionated doses of irradiation suppressed tumor growth in a mouse melanoma model. To study the transcriptomic effects of PpIX, microarray analyses were conducted using HeLa cells with limited proliferation capacity. Based on the p-values (p < 0.01), we selected genes showing altered expression in each treatment group with reference to the non-treatment (NT) group. We detected 290, 196 and 28 upregulated genes, as well as 203, 146 and 36 downregulated genes after a 6 h-long PpIX treatment (1 µg/mL) prior to 3 Gy X-ray irradiation (PpIX-XT), 3 Gy X-ray irradiation alone (XT) and PpIX treatment alone (PpIXT), respectively. Functional analysis revealed that a majority of the regulated genes in the XT and PpIX-XT groups were related to cell-cycle arrest. The XT and PpIX-XT groups differed in the quantity, but not in the quality of their gene expression. The combined effect of PpIX and X-ray irradiation sensitized HeLa cells to X-ray treatment. [ABSTRACT FROM AUTHOR]

As a possible radiosensitizer candidate having biological compatibility, oncotropic property, and X-ray activation capability, contribution of protoporphyrin IX (PpIX) to enhanced generation of reactive oxygen species (ROS) under X-ray and UV irradiations were examined. To identify the kinds of ROS, 2-[6-(4-amino)phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF) and dihydroethidium (DHE) were used together with ethanol as a hydroxyl radical (OH•) quencher. All of the three species of our interest (OH•, superoxide radical (O2•−), and singlet oxygen (1O2)) were enhanced by PpIX under X-ray and UV irradiations in addition to those by radiolysis and photolysis. Its enhancement factors exceeded 1.7 depending on the concentrations of PpIX from 1.5 to 15.0 μg/ml. [Copyright &y& Elsevier]

Since the speed of sound (SOS) reflects tissue characteristics and is expected as an evaluation index of elasticity and water content, the noninvasive measurement of SOS is eagerly anticipated. However, it is difficult to measure the SOS by using an ultrasound device alone. Therefore, we have presented a noninvasive measurement method of SOS using ultrasound (US) and magnetic resonance (MR) images. By this method, we determine the longitudinal SOS based on the thickness measurement using the MR image and the time of flight (TOF) measurement using the US image. The accuracy of SOS measurement is affected by the accuracy of image registration and the accuracy of thickness measurements in the MR and US images. In this study, we address the accuracy improvement in the latter thickness measurement, and present an image-processing-based method for improving the accuracy of thickness measurement. The method was investigated by using in vivo data obtained from a tissue-engineered cartilage implanted in the back of a rat, with an unclear boundary. [ABSTRACT FROM AUTHOR]