Small non-coding RNAs, such as microRNAs (miRNAs), are involved in diverse processes, including organ development and tissue differentiation. Exosomes are small membrane vesicles (30-100 nm in ...diameter) produced by numerous cells. Recently, exosomes have been shown to contain miRNAs. However, the small RNAs contained in exosomes are not fully characterized. In a previous study, we found at least two types of salivary exosome that are different in size and have different proteomes. Studies of salivary exosomal small RNAs are limited to miRNAs. In this study, we examined small RNA transcriptomes using next generation sequencing technology to elucidate a full transcriptome set of small RNAs expressed in the two types of salivary exosomes and in whole saliva (WS). Many types of small RNA, such as miRNA, piwi-interacting RNA (piRNA), small nucleolar RNA (snoRNA) and other small RNAs are contained in salivary exosomes and WS. Among these small RNAs we identified novel miRNA candidates.
•Two types of epoxy resin were used to produce geopolymer composites.•The microstructure and mechanical strength are investigated.•The heat resistance of geopolymer composites was ...examined.•Geopolymer composites behave similarly to the neat geopolymer at high temperature.
This study investigated the performance of fly ash/slag-based geopolymer composites at ambient and extremely high temperatures. Two types of commercially available epoxy resins, bisphenol F epoxy resin and phenol novolac epoxy resin with incorporating amounts of 1 and 2.5 mass%, were used to produce geopolymer composites. The heat resistance test was carried out at 500 °C, 750 °C, and 950 °C. The microstructure and mechanical strength of geopolymers unexposed and exposed to heat were examined. The results show that incorporating a small amount of epoxy resin could improve strength and reduce crack formation. Although the epoxy resin is sensitive to high temperatures, incorporating it into the geopolymer system did not significantly affect the high-temperature resistance of the geopolymer. This finding indicates that geopolymer reinforced with epoxy resin has the potential to be used in the application where exposure to high temperature is required.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Contribution of fly ash to strength development of mortar was investigated.•Contribution of fly ash varied with the replacement ratio and curing temperature.•Expressed cementing efficiency factor as ...log function of cumulative temperature.•Cementing efficiency can be expressed using an appropriate datum temperature.
This study aims to determine the contribution of fly ash to the compressive strength development of mortars cured at different temperatures based on the cementing efficiency factor. The strength development of mortar specimens with different fly ash replacement ratios cured at 10 °C, 20 °C, and 30 °C was analyzed considering the apparent activation energy. Subsequently, the contribution of fly ash was assessed using the cementing efficiency factor. The results indicate that the cementing efficiency factor is significantly affected by the curing temperature and can be estimated using the cumulative temperature and the appropriate datum temperature for fly ash cement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Saliva contains a large number of proteins that participate in the protection of oral tissue. Exosomes are small vesicles (30—100 nm in diameter) with an endosome-derived limiting membrane that are ...secreted by a diverse range of cell types. We have recently demonstrated that exosomes are present in human whole saliva. In this study, we found that whole saliva contained at least two types of exosomes (exosome I and exosome II) that are different in size and protein composition. Proteomic analysis revealed that both types of exosomes contained Alix, Tsg101 and Hsp70, all exosomal markers, immunoglobulin A and polymeric immunoglobulin receptor, whereas they had different protein compositions. Most of dipeptidyl peptidase IV known as CD26 in whole saliva, was present on the exosome II and metabolically active in cleaving chemokines (CXCL11 and CXCL12). Human whole saliva exosomes might participate in the catabolism of bioactive peptides and play a regulatory role in local immune defense in the oral cavity.
Exosomes are derived from various sources, including primary and cultured cell lines and body fluids. It is now evident that they are important for communication between cells. They have, therefore, ...been proposed as potential carriers to deliver drugs to specific sites. In this study, we examined stability of exosomes derived from human saliva. Exosomes were stored at 4°C for up to 20 months and their membrane integrity assessed. Several exosomal markers, such as dipeptidyl peptidase IV (DPP IV; membrane marker) and programmed cell death 6-interacting protein (Alix, lumen marker), were retained intact after 20 months storage at 4°C. Moreover, intact exosomes could be isolated from whole saliva that had been stored at 4°C. Membrane disruption with detergents such as Triton X-100 and Nonidet P-40 caused partial solubilization of DPP IV and release of Alix into the supernatant. In contrast, sodium dodecyl sulfate treatment caused a complete disruption of the membrane. In addition, membrane stability was maintained after freezing and thawing. These results indicated that human saliva-derived exosomes are stable, maintaining their membrane integrity over a long storage period.
Exosomes are small extracellular vesicles containing microRNAs and mRNAs that are produced by various types of cells. We previously used ultrafiltration and size-exclusion chromatography to isolate ...two types of human salivary exosomes (exosomes I, II) that are different in size and proteomes. We showed that salivary exosomes contain large repertoires of small RNAs. However, precise information regarding long RNAs in salivary exosomes has not been fully determined. In this study, we investigated the compositions of protein-coding RNAs (pcRNAs) and long non-protein-coding RNAs (lncRNAs) of exosome I, exosome II and whole saliva (WS) by next-generation sequencing technology. Although 11% of all RNAs were commonly detected among the three samples, the compositions of reads mapping to known RNAs were similar. The most abundant pcRNA is ribosomal RNA protein, and pcRNAs of some salivary proteins such as S100 calcium-binding protein A8 (protein S100-A8) were present in salivary exosomes. Interestingly, lncRNAs of pseudogenes (presumably, processed pseudogenes) were abundant in exosome I, exosome II and WS. Translationally controlled tumor protein gene, which plays an important role in cell proliferation, cell death and immune responses, was highly expressed as pcRNA and pseudogenes in salivary exosomes. Our results show that salivary exosomes contain various types of RNAs such as pseudogenes and small RNAs, and may mediate intercellular communication by transferring these RNAs to target cells as gene expression regulators.
•The strength under the drying condition was attributed to carbonation and suction.•The contributions of the chemical reactions to strength were quantitatively understood.•The relationship between ...the strength and the water content was well established.•Carbonation could increase the strength at the early age of cement-treated soils.
This study investigates the effects of carbonation, water content, and pozzolanic reaction under the drying condition on the strength development of cement-treated soils. Two soil specimen types (i.e., sand mixture and sand–loam mixture) were cured under sealed, drying, and changing water content conditions. The measured compressive strength of the specimens under the drying condition was higher than that under the sealed condition because of carbonation and suction. The relationship between the strength and the water content under the drying condition was established. The progress of the chemical reactions in the specimens was also evaluated. The contributions of cement hydration, carbonation, pozzolanic reaction, and suction to strength development under the drying condition were then quantitatively analyzed. The results indicated that not only cement hydration and pozzolanic reactions, but also carbonation and changes in the water content, substantially contributed to the strength development of cement-treated soils.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and ...their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 10
cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34
cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. ...Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis.
METHODS—We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue.
RESULTS—The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed.
CONCLUSIONS—Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy.
Though behavioral activation (BA) has been shown to be effective for depression, evidence in patients with advanced cancer has not been established. This study aimed to examine the effectiveness of a ...BA program on depression in this population.
A randomized controlled trial with a wait-list control group (waiting group) of 38 patients with advanced cancer and depression will be conducted at three sites in Japan. The BA program consists of seven sessions. Outcome measures will be evaluated at three times in the intervention group; at the entry, at the end of the intervention and 4 months after the end of the intervention and four times in the waiting group: at the entry, before the intervention, at the end of the intervention, and 4 months after the end of the intervention. Primary outcome is Beck Depression Inventory-II (BDI-II) score. To examine the main effect of the intervention, two-way repeated measures analysis of variance (ANOVA) will be conducted, with timing and intervention status as the independent variables and BDI-II score as the dependent variable. One-way repeated measures ANOVA will be conducted to combine data from the intervention and control groups and examine changes in BDI-II scores by timing in both groups. Secondary endpoints (anxiety, quality of life, spirituality, degree of behavioral activation, value, and pain) will be evaluated with rating scales. Two-way repeated measures ANOVA will be conducted to examine whether there are differences between the groups before and after the intervention, with timing and intervention status as the independent variables and scores on each rating scale as the dependent variables.
This multicenter randomized controlled trial is the first study to assess the effectiveness of BA on depression in patients with advanced cancer. Our findings will provide evidence about the effectiveness of BA on depression and provide an intervention option that is acceptable and feasible for the treatment of depression in this population. The results of this study will lead to improved mood and rebuilding to regain life purpose and value in this vulnerable population.
jRCT, jRCT1030210687, Registered 22 March 2022, https://jrct.niph.go.jp/en-latest-detail/jRCT1030210687 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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