Phosphorus intake regulates intestinal function and polyamine metabolism in uremia

Phosphorus intake regulates intestinal function and polyamine metabolism in uremia. This study found that 5/6-nephrectomized uremic rats showed secondary hyperparathyroidism as reflected by an increase in their serum parathyroid hormone (PTH) level in association with a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. These changes recovered partially upon phosphorus restriction. Calcium absorption and gene expression of calbindin-D9k were decreased in uremia and were also improved by phosphorus restriction. In uremia, intestinal spermidine/spermine N1-acetyl-transferase activity was decreased, while ornithine decarboxylase (ODC) activity and its gene expression were potentiated. Enhancement of c-fos and c-jun gene expressions was also observed in uremia. These phenomena suggest that the intestinal villus may proliferate in uremia. Phosphorus restriction prevented increases in the expression of ODC, c-fos and c-jun observed in uremia. Since phosphorus restriction caused a rise in the serum 1,25-(OH)2D level, the role of 1,25-(OH)2D in uremia-induced intestinal dysfunction was examined. A single injection of 1,25-(OH)2D3 to uremic rats caused an increase in the steady-state calbindin-D9k mRNA level, and decreases in steady state c-fos and ODC mRNA levels, suggesting that the deficiency of 1,25-(OH)2D3 is responsible for intestinal dysfunction in uremia. In conclusion, altered polyamine metabolism caused by 1,25-(OH)2D deficiency is intimately involved in intestinal dysfunction and the development of the proliferative state of the intestinal villus in uremia

Localization of silica nanoparticles to lysosome causes lysosomal dysfunction in JEG-3 cells

Kobayashi J., Higashisaka K., Muranaka M., et al. Localization of silica nanoparticles to lysosome causes lysosomal dysfunction in JEG-3 cells. Biochemical and Biophysical Research Communications 736, 150488 (2024); https://doi.org/10.1016/j.bbrc.2024.150488.Nanoparticles have useful functions due to the characteristics conferred on them by an increase in their specific surface area, and they have already been put into practical use in products in various industrial fields. Although exposure to nanoparticles in daily life is unavoidable for pregnant women, studies that evaluate the toxicity of nanoparticles in pregnant women are lacking. To redress this, we have focused on the placenta and have previously revealed that nanoparticles can show placental toxicity. However, there is still little knowledge regarding the behavior of nanoparticles within placental cells, which would enable us to understand their mode of action. Here, we tried to clarify the intracellular localization of silica nanoparticles in placental cells and how this affects placental toxicity. We analyzed the uptake of silica nanoparticles with a diameter of 10 nm (nSP10) into JEG-3 cells, a human choriocarcinoma cell line. Flow cytometry analysis showed that nSP10 labelled with red fluorescence were taken up into JEG-3 cells, and that pre-treatment with the endocytosis inhibitor cytochalasin D inhibited their uptake, suggesting that nSP10 are taken up into JEG-3 cells by the endocytic pathway. Moreover, confocal microscopy revealed that nSP10 are prominently localized in lysosomes. Staining with LysoTracker showed that nSP10 treatment increased the acidic compartment of JEG-3 cells, suggesting lysosome accumulation and swelling. These results indicate that nSP10 taken into placental cells are transferred to lysosomes and may cause lysosomal dysfunction

Guidance for peptide vaccines for the treatment of cancer

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system - a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area. Guidance for Peptide Cancer Vaccines

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

The Creation of School Education Bringing up a Student Carrying Tomorrow (3) : The Valuation of "Compulsory Subjects", "Optional Subjects", and "Integrated Subjects"

The purpose of this study is to show the valuation of "Compulsory Subjects", "Optional Subjects", and "Integrated Subjects", to show the relationship between each subjects and "three abilities", "the ability of recognizing othere senses of value", "the ability of self-expression and communication" and "the ability of decision-making" which defined by the project members. The main result of this study is that we should make up the standards which teachers, students and parents recognize as important abilities

Electrochemically synthesized polymers in molecular imprinting for chemical sensing

This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered