Characterization of common marmoset (Callithrix jacchus) bone marrow-derived mesenchymal stem cells

Abstract: Mesenchymal stem cells (MSCs) could be useful for regenerative medicine because they can beharvested easily from the bone marrow of living donors and the cells can be differentiated into adipogenic, osteogenic, and chondrogenic lineages in vitro. To apply MSCs for the medical treatment of human diseases as regenerative medicine, detailed experimental characterization of the cells is required. Recently, a New World primate, the common marmoset (Callithrix jacchus), has been widely used as a new human disease model because of its ease of handling and breeding. Although common marmoset MSCs have been established and will be used in preclinical studies of regenerative medicine, the characteristics of these cells remain unclear. Aiming to characterize common marmoset MSCs further, we harvested common marmoset bone marrow-derived cells (cmBMDCs) from the femurs of newborn males. We revealed that the morphology of the cells was similar to common marmoset fibroblasts, and extracellular matrix components, such as gelatin and fibronectin, were effective for their proliferation and formation of colony-forming unit fibroblasts. Furthermore, we were able to differentiate cmBMDCs into adipocytes, osteocytes, and chondrocytes in vitro, and they expressed the MSCmarkers CD44, CD73, CD90, and CD105, but their expression decreased with increasing passage number. The data demonstrate that cmBMDCs exhibit characteristics of MSCs and thus it would be beneficial to use these cells in preclinical studies

The MAXI Mission on the ISS: Science and Instruments for Monitoring All Sky X-Ray Images

The MAXI (Monitor of All-sky X-ray Image) mission is the first astronomical payload to be installed on the Japanese Experiment Module-Exposed Facility (JEM-EF) on the ISS. It is scheduled for launch in the middle of 2009 to monitor all-sky X-ray objects on every ISS orbit. MAXI will be more powerful than any previous X-ray All Sky Monitor (ASM) payloads, being able to monitor hundreds of AGN. MAXI will provide all sky images of X-ray sources of about 20 mCrab in the energy band of 2-30 keV from observation on one ISS orbit (90 min), about 4.5 mCrab for one day, and about 1 mCrab for one month. A final detectability of MAXI could be 0.2 mCrab for 2 year observations.Comment: 12 pages, 11 figures, accepted for publication in Publications of the Astronomical Society of Japa

Cell-Free DNA Analysis of Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients by Droplet Digital PCR

Cell-free DNA (cfDNA) analysis may provide a non-invasive diagnostic approach for lung adenocarcinoma patients. Recently, droplet digital PCR (ddPCR) has been developed as a highly sensitive detection method for a low mutant allele percentage. The ddPCR detection limit for epithelial growth factor receptor (EGFR) mutations was evaluated using cell lines, NCI-H1975 for EGFR L858R point mutation and PC-9 for EGFR E746-A750del. Subsequently, detection of EGFR mutations by ddPCR was performed in tumor DNA (tDNA) and cfDNA samples of 19 lung adenocarcinoma patients whose tumor biopsies were already evaluated for EGFR mutations by clamp PCR (13 of L858R, 3 of E746-750del, and 3 of EGFR negative). In 12 cases, immunohistochemical analysis was performed to quantify the number of EGFR L858R-positive cells rate. EGFR point mutation or deletion were detected in 16 tumor DNA samples. In the measurable cfDNA samples, the rate of detection by ddPCR in cfDNA was 61.5% (8/13) for L858R and 100% (3/3) for E746-A750del. A relative correlation was found between the allele fraction (AF) of tDNA and the number of EGFR L858R-positive cells rate. No correlation was found between the AF of tDNA and AF of cfDNA. In our study, cfDNA mutation detection was not associated with clinicopathological features, but cases with high AF of cfDNA did have metastatic lesions. Our study shows that ddPCR enables cfDNA analysis for EGFR L858R and E746-A750del, with a high detection rate. Therefore, cfDNA analysis using ddPCR may complement to tumor biopsy and is beneficial for precision medicine in lung adenocarcinoma patients

In Vitro Transfection of Up-Regulated Genes Identified in Favorable-Outcome Neuroblastoma into Cell Lines

We previously used microarrays to show that high expression of DHRS3, NROB1, and CYP26A1 predicts favorable NB outcomes. Here, we investigated whether expression of these genes was associated with suppression of NB cell (SK-N-SH, NB12, and TGW) growth. We assessed morphology and performed growth, colony-formation, and migration assays, as well as RNA sequencing. The effects of the transient expression of these genes were also assessed with a tetracycline-controlled expression (Tet-On) system. Gene overexpression reduced cell growth and induced morphological senescence. Gene-expression analysis identified pathways involving cellular senescence and cell adhesion. In these cells, transduced gene dropout occurred during passage, making long-term stable gene transfer difficult. Tet-On-induced gene expression caused more pronounced cell-morphology changes. Specifically, DHRS3 and NROB1 led to rapid inhibition and arrest of cell growth, though CYP26A1 did not affect cell-growth rate or cell cycle. DHRS3 arrested the cell cycle by interacting with the all-trans-retinol pathway and drove differentiation and senescence in tumors. Overexpression of these genes reduced the malignant grade of these cells. A new therapeutic strategy might be the induction of these genes, as they suppress the growth of high-risk neuroblastoma and lead to differentiation and senescence

Recording the Fragrance of 15 Types of Medicinal Herbs and Comparing Them by Similarity Using the Electronic Nose FF-2A

Medical herbs have been recognized till now as having different constituents that act on the human body. However, the fragrance of herbs is a complex mixture of odors, which makes it difficult to qualify or quantify the scent objectively on the human sense of smell. In this study, aromas of 15 medicinal herbs were recorded using an electronic nose FF-2A, and their characteristics were compared with aroma samples of wine such as Le Nez du Vin, to determine which wine aromas are similar to each medicinal herb. Thereafter, the aromas of the 15 herbs were standardized to create a reference axis for the aroma of each herb, and the similarity of tea herbs to the reference axis was examined. Additionally, the results were compared with those obtained by gas chromatography-mass spectrometry (GC-MS). In FF-2A, the measured scent is recorded as an absolute value. We succeeded in calculating the similarity of the scents of other herbs with the axes of the scent of each herb by standardizing their scents and creating new axis data. Conversely, although GC-MS is able to identify the components and concentrations of fragrances, an electronic nose can analyze fragrances in a way that is uncommon with GC-MS, such as comparison of similarities between fragrances

Recording the Fragrance of 15 Types of Medicinal Herbs and Comparing Them by Similarity Using the Electronic Nose FF-2A

Medical herbs have been recognized till now as having different constituents that act on the human body. However, the fragrance of herbs is a complex mixture of odors, which makes it difficult to qualify or quantify the scent objectively on the human sense of smell. In this study, aromas of 15 medicinal herbs were recorded using an electronic nose FF-2A, and their characteristics were compared with aroma samples of wine such as Le Nez du Vin, to determine which wine aromas are similar to each medicinal herb. Thereafter, the aromas of the 15 herbs were standardized to create a reference axis for the aroma of each herb, and the similarity of tea herbs to the reference axis was examined. Additionally, the results were compared with those obtained by gas chromatography-mass spectrometry (GC-MS). In FF-2A, the measured scent is recorded as an absolute value. We succeeded in calculating the similarity of the scents of other herbs with the axes of the scent of each herb by standardizing their scents and creating new axis data. Conversely, although GC-MS is able to identify the components and concentrations of fragrances, an electronic nose can analyze fragrances in a way that is uncommon with GC-MS, such as comparison of similarities between fragrances

The Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Association with Physical Function and Prognosis in Patients with Acute Coronary Syndrome

It is believed that patients with acute coronary syndrome (ACS) are at an increased risk of nonalcoholic fatty liver disease (NAFLD), which can lead to sarcopenia and physical dysfunction. However, the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and physical dysfunction and prognosis remains unclear. We investigated the prevalence of MAFLD in patients with ACS to assess the relationship between MAFLD and muscle strength, walking speed, and 6-min walking distance (6 MWD). We reviewed patients with ACS who were assessed for hepatic steatosis using the fatty liver index, and the results were further assessed to determine the presence of MAFLD. Among 479 enrolled hospitalized patients, MAFLD was identified in 234 (48.9%) patients. Multiple regression analysis revealed that MAFLD was independently associated with lower leg strength, gait speed, and 6 MWD (leg strength, p = 0.020; gait speed, p = 0.003 and 6 MWD, p = 0.011). Furthermore, in multivariate Poisson regression models after adjustment for clinical confounding factors, combined MAFLD and reduced physical functions were significantly associated with a higher incidence of clinical events. MAFLD is common in hospitalized patients with ACS and is associated with impaired physical function. Also, the coexistence of MAFLD and lower physical function predict the incidence of clinical events in patients with ACS

The Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Association with Physical Function and Prognosis in Patients with Acute Coronary Syndrome

It is believed that patients with acute coronary syndrome (ACS) are at an increased risk of nonalcoholic fatty liver disease (NAFLD), which can lead to sarcopenia and physical dysfunction. However, the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and physical dysfunction and prognosis remains unclear. We investigated the prevalence of MAFLD in patients with ACS to assess the relationship between MAFLD and muscle strength, walking speed, and 6-min walking distance (6 MWD). We reviewed patients with ACS who were assessed for hepatic steatosis using the fatty liver index, and the results were further assessed to determine the presence of MAFLD. Among 479 enrolled hospitalized patients, MAFLD was identified in 234 (48.9%) patients. Multiple regression analysis revealed that MAFLD was independently associated with lower leg strength, gait speed, and 6 MWD (leg strength, p = 0.020; gait speed, p = 0.003 and 6 MWD, p = 0.011). Furthermore, in multivariate Poisson regression models after adjustment for clinical confounding factors, combined MAFLD and reduced physical functions were significantly associated with a higher incidence of clinical events. MAFLD is common in hospitalized patients with ACS and is associated with impaired physical function. Also, the coexistence of MAFLD and lower physical function predict the incidence of clinical events in patients with ACS