Effects of a video-viewing intervention with positive word stimulation on the depressive symptoms of older patients with cardiac disease and subthreshold depression: a pilot randomized controlled trial protocol.

Background: Intervention for older patients with cardiac disease and subthreshold depression (StD) may be an effective strategy to prevent the development of major depressive disorder. The subliminal priming with supraliminal reward stimulation (SPSRS) website developed by us is an advanced intervention that can improve depressive symptoms in individuals with StD by presenting positive word stimuli in videos. However, its efficacy for treating depressive symptoms in older patients with cardiac disease and StD has not been investigated.

descSPIM: an affordable and easy-to-build light-sheet microscope optimized for tissue clearing techniques.

Despite widespread adoption of tissue clearing techniques in recent years, poor access to suitable light-sheet fluorescence microscopes remains a major obstacle for biomedical end-users. Here, we present descSPIM (desktop-equipped SPIM for cleared specimens), a low-cost ($20,000-50,000), low-expertise (one-day installation by a non-expert), yet practical do-it-yourself light-sheet microscope as a solution for this bottleneck. Even the most fundamental configuration of descSPIM enables multi-color imaging of whole mouse brains and a cancer cell line-derived xenograft tumor mass for the visualization of neurocircuitry, assessment of drug distribution, and pathological examination by false-colored hematoxylin and eosin staining in a three-dimensional manner.

Development of a novel co-culture system using human pancreatic cancer cells and human iPSC-derived stellate cells to mimic the characteristics of pancreatic ductal adenocarcinoma in vitro.

Pancreatic ductal adenocarcinoma (PDAC) is a serious disease with poor prognosis and prone to chemotherapy resistance. It is speculated that the tumor microenvironment (TME) of PDAC contributes to these characteristics. However, the detailed mechanisms of interactions between pancreatic cancer cells and stroma in the TME are unclear.

Highly Sensitive Detection of Human Pluripotent Stem Cells by Loop-Mediated Isothermal Amplification.

For safe regenerative medicines, contaminated or remaining tumorigenic undifferentiated cells in cell-derived products must be rigorously assessed through sensitive assays. Although in vitro nucleic acid tests offer particularly sensitive tumorigenicity-associated assays, the human pluripotent stem cell (hPSC) detectability is partly constrained by the small input amount of RNA per test. To overcome this limitation, we developed reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays that are highly gene specific and robust against interfering materials.

Copper-Catalyzed Enantioselective Hydrosilylation of gem-Difluorocyclopropenes Leading to a Stereochemical Study of the Silylated gem-Difluorocyclopropanes.

Optically active cyclopropanes have been widely investigated especially from the views of pharmaceutical and agrochemical industries, and substituting one of the methylenes with the difluoromethylene unit should be promising for developing novel biologically relevant compounds and functional materials. In this paper, the copper-catalyzed enantioselective hydrosilylation of gem-difluorocyclopropenes to provide the corresponding chiral gem-difluorocyclopropanes is presented. The use of copper(I) chloride, chiral ligands including bidentate BINAPs and monodentate phosphoramidites, and silylborane Me PhSi-Bpin accompanying sodium tert-butoxide in methanol was appropriate for the enantioselective hydrosilylation of the strained C=C double bond, and the resultant chiral difluorinated three-membered ring was unambiguously characterized.

High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development.

Primary human hepatocytes are widely used to evaluate liver toxicity of drugs, but they are scarce and demanding to culture. Stem cell-derived hepatocytes are increasingly discussed as alternatives. To obtain a better appreciation of the molecular processes during the differentiation of induced pluripotent stem cells into hepatocytes, we employ a quantitative proteomic approach to follow the expression of 9,000 proteins, 12,000 phosphorylation sites, and 800 acetylation sites over time.

Clever Experimental Designs: Shortcuts for Better iPSC Differentiation.

For practical use of pluripotent stem cells (PSCs) for disease modelling, drug screening, and regenerative medicine, the cell differentiation process needs to be properly refined to generate end products with consistent and high quality. To construct and optimize a robust cell-induction process, a myriad of cell culture conditions should be considered. In contrast to inefficient brute-force screening, statistical design of experiments (DOE) approaches, such as factorial design, orthogonal array design, response surface methodology (RSM), definitive screening design (DSD), and mixture design, enable efficient and strategic screening of conditions in smaller experimental runs through multifactorial screening and/or quantitative modeling.

Human Organoid and Supporting Technologies for Cancer and Toxicological Research.

Recent progress in the field of organoid-based cell culture systems has enabled the use of patient-derived cells in conditions that resemble those in cancer tissue, which are better than two-dimensional (2D) cultured cell lines. In particular, organoids allow human cancer cells to be handled in conditions that resemble those in cancer tissue, resulting in more efficient establishment of cells compared with 2D cultured cell lines, thus enabling the use of multiple patient-derived cells with cells from different genetic background, in keeping with the heterogeneity of the cells. One of the most valuable points of using organoids is that human cells from either healthy or cancerous tissue can be used.

Robust parameter design of human induced pluripotent stem cell differentiation protocols defines lineage-specific induction of anterior-posterior gut tube endodermal cells.

Tissues and cells derived from pluripotent stem cells (PSC) are likely to become widely used in disease modeling, drug screening, and regenerative medicine. For these applications, the in vitro PSC differentiation process must be elaborately investigated and controlled to reliably obtain the desired end products. However, because traditional experimental methods, such as one factor at a time or brute-force approaches, are impractical for detailed screening of complex PSC cultivation conditions, more strategic and effective screening based on statistical design of experiments (DOE) ought to be indispensable.

Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media.

Advances in organoid technology have broadened the number of target diseases and conditions in which human induced pluripotent stem cell (iPSC)-based regenerative medicine can be applied; however, mass production of organoids and the development of chemically defined, animal origin-free (CD-AOF) media and supplements are unresolved issues that hamper the clinical applicability of these approaches. CD-AOF media and supplements ensure the quality and reproducibility of culture systems by lowering lot-to-lot variations and the risk of contamination with viruses or toxins. We previously generated liver organoids from iPSCs, namely iPSC-liver buds (iPSC-LBs), by mimicking the organogenic interactions among hepatocytes, endothelial cells (ECs), and mesenchymal cells (MCs) and recently reported the mass production of iPSC-LBs derived entirely from iPSCs (all iPSC-LBs), which should facilitate their large-scale production for the treatment of liver failure.

Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method.

To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture.

Robust detection of undifferentiated iPSC among differentiated cells.

Recent progress in human induced pluripotent stem cells (iPSC) technologies suggest that iPSC application in regenerative medicine is a closer reality. Numerous challenges prevent iPSC application in the development of numerous tissues and for the treatment of various diseases. A key concern in therapeutic applications is the safety of the cell products to be transplanted into patients.

Enantioselective Functionalization of Difluorocyclopropenes Catalyzed by Chiral Copper Complexes: Proposal for Chiral -Dimethyl and -Butyl Analogues.

The highly enantioselective copper/chiral phosphine-catalyzed hydro-, bora-, and carbo-metalations of difluorocyclopropenes with PHMS [H-Si], H-BPin, (BPin), and (CH)Zn [Zn-Me] are shown to regiodivergently afford highly enantioenriched and functionalized difluorocyclopropanes. These examples can be viewed as the first successful syntheses of "chiral" -dimethyl and -butyl analogues.

Publisher Correction: Fgf10 is essential for limb and lung formation.

In the version of the paper initially published, Fig. 5a was inadvertently duplicated and presented as both Fig. 5a and 5f, and the correct image for Fig.

Recapitulation of hepatitis B virus-host interactions in liver organoids from human induced pluripotent stem cells.

Therapies against hepatitis B virus (HBV) have improved in recent decades; however, the development of individualized treatments has been limited by the lack of individualized infection models. In this study, we used human induced pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that inherited the genetic background of the donor, and evaluated its application in modeling HBV infection and exploring virus-host interactions. To establish a functional hiPSC-LO, we cultured hiPSC-derived endodermal, mesenchymal, and endothelial cells with a chemically defined medium in a three-dimensional microwell culture system.

Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling.

Timely controlled oxygen (O) delivery is crucial for the developing liver. However, the influence of O on intercellular communication during hepatogenesis is unclear. Using a human induced pluripotent stem cell-derived liver bud (hiPSC-LB) model, we found hypoxia induced with an O-permeable plate promoted hepatic differentiation accompanied by TGFB1 and TGFB3 suppression.

Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation.

Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by "self-condensation" culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets.

Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids.

Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2 posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm.

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells.

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme.

Multilineage communication regulates human liver bud development from pluripotency.

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture.

Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells.

Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promotes tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue.

Liver Regeneration Using Cultured Liver Bud.

Here, we describe a protocol to develop a three-dimensional (3D) liver bud-like tissue from human iPSCs in vitro. This method mainly consists of two parts: (1) hepatic endoderm (HE) differentiation from human iPSCs in 2D culture and (2) co-culturing iPSC-HE with endothelial and mesenchymal cells. First, iPSCs were differentiated into definitive endoderm (DE) cells, and the DE cells were differentiated into HE cells, which were then co-cultured with endothelial cells and mesenchymal cells on Matrigel-coated plastic plates or micropattern plates.

Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism.

Liver bud progenitors experience a transient amplification during the early organ growth phase, yet the mechanism responsible is not fully understood. Collective evidence highlights the specific requirements in stem cell metabolism for expanding organ progenitors during organogenesis and regeneration. Here, transcriptome analyses show that progenitors of the mouse and human liver bud growth stage specifically express the gene branched chain aminotransferase 1, encoding a known breakdown enzyme of branched-chain amino acids (BCAAs) for energy generation.

Correlation between brain damage, associated biomarkers, and medication in psychiatric inpatients: A cross-sectional study.

Background: We clarified the correlation between brain damage, associated biomarkers and medication in psychiatric patients, because patients with schizophrenia have an increased risk of stroke.

Methods: The cross-sectional study was performed from January 2013 to December 2015. Study participants were 96 hospitalized patients (41 men and 55 women) in the Department of Psychiatry at Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.