Directed differentiation of human mesenchymal stromal cells into functional endothelial cells having IKAROS-mediated immune tolerance properties.

We report an efficient method for the directed differentiation of mesenchymal stromal cells derived from embryonic stem cells (EMSCs) into functional endothelial cells (EC), addressing the challenges of direct conversion, such as cellular senescence. We found that transduction of one transcription factor, ER71, was required for the efficient derivation of induced endothelial cells from EMSCs (MiECs). Addition of transforming growth factor-β inhibitor (SB431542), vascular endothelial growth factor, and ascorbic acid to the culture media enhanced the differentiation efficiency.

Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that primarily affects the enthesis and may culminate in bony ankylosis of the spine. Despite TNF inhibitor (TNFi) being foundational in managing active inflammation, 30-40% of patients with AS remain non-responsive. Through longitudinal and multi-omics profiling of peripheral blood mononuclear cells from TNFi-receiving patients with AS, here we reveal that elevated type I IFN signatures at baseline are associated with poor TNFi response, leading to a paradoxical enhancement of IFN signatures and Th17 responses following TNFi therapy.

Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals.

While radioactive iodine therapy (RAIT) has been an effective treatment for thyroid cancer, its link to clonal hematopoiesis (CH) has been yet underexplored. In this study, error-corrected sequencing (median depth: 1926×) of 93 CH-related genes was performed from the blood samples of 358 thyroid cancer patients, including 110 controls (no RAIT) and 248 RAIT recipients. RAIT recipients were stratified into low- and high-dose groups using a 7.

Physician-Scientist Training System and Development Strategies in Korea.

Physician-scientists play a pivotal role in bridging clinical practice and biomedical research, advancing medical science, and tackling complex healthcare challenges. In South Korea, the declining number of medical doctors engaging in basic medical sciences has prompted the implementation of various training initiatives since the 2000s. Notable initiatives, such as the Integrated Physician-Scientist Training Program (2019) and the Global Physician-Scientist Training Program (2024), aim to cultivate multidisciplinary physician-scientists capable of addressing unmet medical needs.

Synergistic/antagonistic antimicrobial effects of cosmetic ingredients in combination with 1,2-hexanediol.

With the rise of the clean beauty trend in the cosmetics and personal care industry, consumers' interest in cosmetic ingredients, especially preservatives, continues to grow. Paraben, previously the most used preservative in cosmetics, has been excluded from many products owing to its potential risks. Therefore, a movement to lower the content of various preservatives is ongoing.

Simultaneous Epigenetic and Gene Expression Profiling at Single Cell Resolution Uncovers Stem-Like Treg Subsets Induced With Oligonucleotide Expansion in Humans.

Tregs play a central role in maintaining immune tolerance. Recent progress in the clinical application of Tregs underscores their potential for cell therapy. Nevertheless, a notable hurdle remains in producing functional Tregs .

Assembly of glioblastoma tumoroids and cerebral organoids: a 3D in vitro model for tumor cell invasion.

Glioblastoma (GBM) has a fatal prognosis because of its aggressive and invasive characteristics. Understanding the mechanism of invasion necessitates an elucidation of the relationship between tumor cells and the tumor microenvironment. However, there has been a scarcity of suitable models to investigate this.

Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells.

The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN.

Genetic and epigenetic alterations in aging and rejuvenation of human.

All the information essential for life is encoded within our genome and epigenome, which orchestrates diverse cellular states spatially and temporally. In particular, the epigenome interacts with internal and external stimuli, encoding and preserving cellular experiences, and it serves as the regulatory base of the transcriptome across diverse cell types. The emergence of single-cell transcriptomic and epigenomic data collection has revealed unique omics signatures in diverse tissues, highlighting cellular heterogeneity.

Blockade of STING activation alleviates microglial dysfunction and a broad spectrum of Alzheimer's disease pathologies.

Abnormal glial activation promotes neurodegeneration in Alzheimer's disease (AD), the most common cause of dementia. Stimulation of the cGAS-STING pathway induces microglial dysfunction and sterile inflammation, which exacerbates AD. We showed that inhibiting STING activation can control microglia and ameliorate a wide spectrum of AD symptoms.

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.

Microglia Gravitate toward Amyloid Plaques Surrounded by Externalized Phosphatidylserine via TREM2.

Microglia play a crucial role in synaptic elimination by engulfing dystrophic neurons via triggering receptors expressed on myeloid cells 2 (TREM2). They are also involved in the clearance of beta-amyloid (Aβ) plaques in Alzheimer's disease (AD); nonetheless, the driving force behind TREM2-mediated phagocytosis of beta-amyloid (Aβ) plaques remains unknown. Here, using advanced 2D/3D/4D co-culture systems with loss-of-function mutations in TREM2 (a frameshift mutation engineered in exon 2) brain organoids/microglia/assembloids, it is identified that the clearance of Aβ via TREM2 is accelerated by externalized phosphatidylserine (ePtdSer) generated from dystrophic neurons surrounding the Aβ plaques.

Image-based deep learning model using DNA methylation data predicts the origin of cancer of unknown primary.

Cancer of unknown primary (CUP) is a rare type of metastatic cancer in which the origin of the tumor is unknown. Since the treatment strategy for patients with metastatic tumors depends on knowing the primary site, accurate identification of the origin site is important. Here, we developed an image-based deep-learning model that utilizes a vision transformer algorithm for predicting the origin of CUP.

Higher Genetic Risk for Type 2 Diabetes Is Associated With a Faster Decline of β-Cell Function in an East Asian Population.

Objective: While most genetic variants of type 2 diabetes (T2D) are suggested to be associated with β-cell dysfunction cross sectionally, their association with the longitudinal change of β-cell function remains largely unknown.

Research Design And Methods: We analyzed data from 6,311 participants without T2D at baseline (mean [SD] age 51.6 [8.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons.

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.

Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression.

Brain hypothyroidism silences the immune response of microglia in Alzheimer's disease animal model.

Thyroid hormone (TH) imbalance is linked to the pathophysiology of reversible dementia and Alzheimer's disease (AD). It is unclear whether tissue hypothyroidism occurs in the AD brain and how it affects on AD pathology. We find that decreased iodothyronine deiodinase 2 is correlated with hippocampal hypothyroidism in early AD model mice before TH alterations in the blood.

Placental expression quantitative trait loci in an East Asian population.

Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue.

Targeting the mA RNA methyltransferase METTL3 attenuates the development of kidney fibrosis.

Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N-methyladenosine (mA) RNA methylation is associated with organ fibrosis. We investigated mA profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model).

Potential Perturbations of Critical Cancer-regulatory Genes in Triple-Negative Breast Cancer Cells Within the Humanized Microenvironment of Patient-derived Xenograft Models.

Purpose: In this study, we aimed to establish humanized patient-derived xenograft (PDX) models for triple-negative breast cancer (TNBC) using cord blood (CB) hematopoietic stem cells (HSCs). Additionally, we attempted to characterize the immune microenvironment of the humanized PDX model to understand the potential implications of altered tumor-immune interactions in the humanized PDX model on the behavior of TNBC cells.

Methods: To establish a humanized mouse model, high-purity CD34 HSCs from CB were transplanted into immunodeficient NOD scid γ mice.