Guided differentiation of embryonic stem cells into Pdx1-expressing regional-specific definitive endoderm

The generation of specific lineages of the definitive endoderm from embryonic stem (ES) cells is an important issue in developmental biology, as well as in regenerative medicine. This study demonstrates that ES cells are induced sequentially into regional-specific gut endoderm lineages, such as pancreatic, hepatic, and other cell lineages, when they are cultured directly on a monolayer of mesoderm-derived supporting cells. A detailed chronological analysis revealed that Activin, fibroblast growth factor, or bone morphogenetic protein signals are critical at various steps and that additional short-range signals are required for differentiation into Pdx1-expressing cells. Under selective culture conditions, definitive endoderm (47%) or Pdx1-positive pancreatic progenitors (30%) are yielded at a high efficiency. When transplanted under the kidney capsule, the Pdx1-positive cells further differentiated into all three pancreatic lineages, namely endocrine, exocrine, and duct cells.     

Central genetic alterations common to all HCV-positive, HBV-positive and non-B, non-C hepatocellular carcinoma: a new approach to identify novel tumor markers

Hepatocellular carcinoma (HCC) is a common malignancy, but the prognosis remains poor due to the lack of sensitive diagnostic markers. To gain insight into the central molecular features common to all types of HCC, and to identify novel diagnostic markers or therapeutic targets for HCC, we performed a gene expression profiling analysis using a high throughput RT-PCR system. After examining the mRNA expression of 3,072 genes in 204 (119 tumor and 85 non-tumor) liver samples, we identified differential gene expression between the HCV group (n=80), HBV group (n=19) and non-B, non-C group (n=20) with a principal component analysis and a correlation spectrum analysis. After selection of genes differentially expressed between tumor and non-tumor tissues (p<0.01) within each HCC group, a total of 51 differentially expressed genes (23 upregulated and 28 downregulated genes) were found to be common to the three HCC groups. Gene Ontology grouping analysis revealed that genes with functions related to cell proliferation or differentiation and genes encoding extracellular proteins were found to be significantly enriched in these 51 common genes. Using an atelocollagen-based cell transfection array for functional analysis of eight upregulated genes, five (CANX, FAM34A, PVRL2, LAMR1, and GBA) significantly inhibited cellular apoptosis by two independent assays. In conclusion, we identified 51 differentially expressed genes, common to all HCC types. Among these genes, there was a high incidence of anti-apoptotic activity. This combination approach with the advanced statistical methods and the bioinformatical analysis may be useful for finding novel molecular targets for diagnosis and therapy.     

Gene trap mutagenesis in mice: new perspectives and tools in cancer research

The complete human DNA sequence of the human genome was published in 2004 and we entered the postgenomic era. However, many studies showed that gene function is much more complex than we expected, and that mutation of disease genes does not give any clue for molecular mechanisms for disease development. Since the first report on gene knockout mice in 1989, knockout mice have been shown to be a powerful tool for functional genomics and for the dissection of developmental processes in human diseases. In accordance with this successful application of knockout mice, three major mouse knockout programs are now underway worldwide, to mutate all protein-encoding genes in mouse embryonic stem cells using a combination of gene trapping and gene targeting. We developed the exchangeable gene trap method suitable for large scale mutagenesis in mice. In this method we can produce null mutation and post-insertional modification, enabling replacement of the marker gene with a gene of interest and conditional knockout. We herein discuss the effect of this gene-driven type approach for cancer research, especially for finding the genes that are related to cancer, but are paid little attention in hypothesis-driven cancer research. ( Cancer Sci 2008; 99: 1–6)     

Cost-utility analysis of a one-time supervisor telephone contact at 6-weeks post-partum to prevent extended sick leave following maternity leave in The Netherlands: results of an economic evaluation alongside a randomized controlled trial

Background  

Working women of childbearing age are a vital part of the population. Following childbirth, this group of women can experience a myriad of physical and mental health problems that can interfere with their ability to work. Currently, there is little known about cost-effective post-partum interventions to prevent work disability. The purpose of the study was to evaluate whether supervisor telephone contact (STC) during maternity leave is cost-effective from a societal perspective in reducing sick leave and improving quality-adjusted life years (QALYs) compared to common practice (CP).     

Behavioral abnormalities of fetal growth retardation model rats with reduced amounts of brain proteoglycans

Fetal growth retardation (FGR) is a critical problem in the neonatal period, because a substantial population of infants born with FGR go on to develop various developmental disorders. In the present study, we produced FGR model rats by continuous administration of a synthetic thromboxane A₂ analogue (STA₂) to pregnant rats. The FGR pups exhibited a significant delay in postnatal neurological development. Moreover, behavioral analyses revealed the presence of a learning disability in juvenile FGR male rats. To investigate the mechanism underlying the neurological disorders, histological and biochemical analyses of the brain of FGR rats were performed. The density of neurons in the cortical plate of an FGR brain was low compared with the brains of a similarly aged, healthy rat. Consistent with this finding, the density of TUNEL-positive cells was higher in the cortical plate of FGR brains. Western blot analyses showed that the levels of three brain-specific chondroitin sulfate proteoglycans (CSPGs), neurocan, phosphacan, and neuroglycan C, were all significantly reduced in the brain of neonatal FGR rats compared with those of the control. The reduction of CSPG-levels and morphological changes in the brain may be relevant to neurological dysfunction in FGR.     

Can cognitive leisure activity prevent cognitive decline in older adults? A systematic review of intervention studies

The aims of this systematic review were to investigate what kind of cognitive leisure activities have been used in intervention studies targeting older adults, and whether these activities improve cognitive function or inhibit cognitive decline. Based on the PRISMA declaration, we searched keywords using three electronic databases: PubMed, PsycINFO and PsycARTICLES. Intervention studies involving cognitive leisure activities with cognitive assessments set as outcomes were included. We regarded cognitive leisure activities as activities for enjoyment or well‐being that cause intellectual stimulation (e.g. reading, playing board games). To investigate the influence of each activity on cognitive domains, multicomponent programs (e.g. combined music and art) were excluded. In total, 20 studies were included in the evaluation. Consequently, intervention studies related to arts, writing, board games, reading, handicrafts, a crossword puzzle and learning computer skills were identified. Of the 20 studies, 13 showed improvement in some cognitive domain. In 12 of these 13 studies, the intervention effects were not observed in a specific cognitive domain; rather, the intervention effects were observed across multiple cognitive domains and on working memory. The results of the present review suggest that cognitive function in older adults can be improved through cognitive leisure activity interventions. Activities related to learning new skills, that cause strong intellectual stimulation and that include communication elements were considered particularly effective tools. However, as the number of studies is small, more high‐quality research needs to be accumulated. Geriatr Gerontol Int 2019; 19: 469–482 .