Publications by authors named "Narae Park"

Hypoimmunogenic universal induced pluripotent stemn (iPS) cells were generated through the targeted disruption of key genes, including human leukocyte antigen (HLA)-A, HLA-B and HLA-DR alpha (DRA), using the CRISPR-Cas9 system. This approach aimed to minimize immune recognition and enhance the potential of iPS cells for allogeneic therapy. Heterozygous iPS cells were used for guide RNA design and validation to facilitate the knockout (KO) of the HLA-A, HLA-B and HLA-DRA genes.

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Objective: To evaluate the impact of the emergency department (ED) Multi-Visit Patient (MVP) Program, a novel team-based approach to supporting patients with frequent ED utilization.

Study Setting And Design: The ED MVP Program identified patients with frequent ED visits, conducted comprehensive chart reviews, and implemented tailored care plans to address healthcare barriers and social determinants of health. A comparison group included eligible patients who did not receive the intervention as well as those not yet treated at a given month.

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Objectives: Decades of research indicate that volunteering is associated with better health for the volunteer beyond the selection effects based on health. However, little is known about potential heterogeneity in health outcomes associated with volunteering in the context of good or poor health. This study addresses this gap by focusing on the frailty index (FI) to investigate the volunteering-health nexus across the population frailty distribution ranging from fit to frail.

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Objective: To compare fertility in India to both low-to-middle-income and high-income countries (LMICs and HICs) and describe the patterns that have accompanied India's transition to low fertility.

Methods: We use data from the Demographic and Health Surveys (DHS), the United Nations (UN), and the Organisation for Economic Co-operation and Development (OECD) to observe factors associated with fertility decline in 36 Indian states and 76 countries.

Results: Although fertility in India has declined to levels similar to HICs, women's entry into marriage and initiation of childbearing are more in line with patterns found in LMICs.

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CDK12 is overexpressed in HER2-positive breast cancers and promotes tumorigenesis and trastuzumab resistance. Thus CDK12 is a good therapeutic target for the HER2-positive breast tumors resistant to trastuzumab. We previously reported a novel purine-based CDK inhibitor with an ability to degrade cyclinK.

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Liquid chromatography-tandem mass spectrometry (LC-MS)-based profiling of proteomes with isobaric tag labeling from low-quantity biological and clinical samples, including needle-core biopsies and laser capture microdissection, has been challenging due to the limited amount and sample loss during preparation. To address this problem, we developed OnM (On-Column from Myers et al. and mPOP)-modified on-column method combining freeze-thaw lysis of mPOP with isobaric tag labeling of On-Column method to minimize sample loss.

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Article Synopsis
  • * The treatment resulted in significant improvements in the mice's motor skills and balance, as well as better preservation of brain cells and increased protein levels in specific neurons.
  • * Additionally, hMSC injections enhanced the levels of beneficial neurotrophic factors and reduced inflammation, indicating their potential as a therapeutic approach to mitigate ataxia symptoms and cerebellar damage.
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  • - The study focuses on a co-culture system where different cell types are grown together to simulate their natural environment, allowing for a more accurate analysis of their secreted proteins, known as the secretome.
  • - Researchers used a method involving a mouse mutant enzyme to incorporate a special amino acid into proteins, which helped isolate and identify the specific secretome from the targeted cell type while minimizing contamination from other sources.
  • - They successfully identified up to 719 secreted proteins and applied this analysis to mesenchymal stem cells, predicting their potential therapeutic effects on osteoarthritis based on the secretome profiles obtained.
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Phosphorylation is a crucial component of cellular signaling cascades. It controls a variety of biological cellular functions, including cell growth and apoptosis. Owing to the low stoichiometry of phosphorylated proteins, the enrichment of phosphopeptides prior to LC-MS/MS is necessary for comprehensive phosphoproteome analysis, and quantitative phosphoproteomic workflows are typically limited by the amount of sample required.

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Background And Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE.

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Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1-34 and 107-139); mcPTHrP 1-34+107-139 using a minicircle vector.

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  • The study focuses on the role of matrix metalloproteinase-2 (MMP-2) in the progression of metastatic colorectal cancer (CRC) and highlights a lack of understanding about its effects in clinical scenarios.
  • An analysis was conducted on CRC patient plasma proteome, cancer secretome after MMP-2 knockdown, and existing CRC tissue proteome data, revealing a protein cluster linked to epithelial-to-mesenchymal transition (EMT).
  • The findings suggest that increased levels of MMP-2 and CD9-integrin, along with the activation of focal adhesion kinase signaling, contribute to the higher invasiveness observed in metastatic CRC as the disease advances.
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Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of or . Current strategies for treating OI are not curative.

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Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal size, minicircles exhibit relatively high safety and efficient delivery of genes of interest into cells.

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Hypoxic environment is essential for chondrocyte maturation and longitudinal bone growth. Although hypoxia-inducible factor 1 alpha (Hif-1α) has been known as a key player for chondrocyte survival and function, the function of Hif-2α in cartilage is mechanistically and clinically relevant but remains unknown. Here we demonstrated that Hif-2α was a novel inhibitor of chondrocyte maturation through downregulation of Runx2 stability.

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  • CT-derived skeletal muscle area (SMA) and skeletal muscle radiodensity (SMD) provide insights into muscle quantity and quality, but their ability to predict muscle function is not well understood.
  • A study involving 1,523 older adults found that those with low jump power had lower SMA, SMD, and grip strength, indicating a relationship between muscle quality and function.
  • SMD was found to be a significant predictor of low jump power, more so than SMA, suggesting that SMD could be a valuable marker for assessing muscle function in older adults.
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Early osteoarthritis (OA)-like symptoms are difficult to study owing to the lack of disease samples and animal models. In this study, we generated induced pluripotent stem cell (iPSC) lines from a patient with a radiographic early-onset finger osteoarthritis (efOA)-like condition in the distal interphalangeal joint and her healthy sibling. We differentiated those cells with similar genetic backgrounds into chondrogenic pellets (CPs) to confirm efOA.

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  • Cigarette smoking is a known risk factor for rheumatoid arthritis (RA), but the precise mechanisms behind its aggravation of the disease have not been fully understood; this study explores those mechanisms using an experimental model.
  • Mice exposed to cigarette smoke while being induced with collagen-induced arthritis (CIA) experienced a faster onset of the disease and showed increased citrullination in lung and joint tissues, with significant changes noted in tracheal cartilage.
  • The findings suggest that targeting tracheal citrullination caused by cigarette smoke could be a potential strategy for preventing or reducing the severity of arthritis in those at risk.
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Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors.

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  • A 3D culture system mimicking the natural environment of bone is important for creating bone-like material in labs.
  • This study uses plant-derived cellulose scaffolds to support the growth of stem cells turning into osteoblasts (bone cells).
  • Among the tested materials, apple scaffolds with 300 μm pores performed the best, leading to successful tissue generation that could be implanted in rats, promoting bone formation.
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  • Metabolomics studies the unique metabolites involved in cellular processes, helping to diagnose rheumatoid arthritis (RA) and osteoarthritis (OA) by identifying disease biomarkers.
  • The study compared the metabolic profiles of fibroblast-like synoviocyte (FLS) cells and induced pluripotent stem cells (iPSCs) from RA and OA patients, revealing 37 detectable metabolites using advanced techniques.
  • Key findings indicated that certain metabolites, particularly nicotinamide (NAM), were significantly higher in RA iPSCs, contributing to their greater proliferation, while treatment with a NAM inhibitor notably reduced this proliferation in RA iPSCs.
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  • - Peptic ulcer disease is the leading cause of acute gastrointestinal bleeding, but acquired hemophilia A is a rare condition that causes bleeding due to the body's own antibodies attacking clotting factor VIII.
  • - A 78-year-old man visited the Emergency Department with symptoms of melena and was treated for Dieulafoy's lesions through endoscopic cauterization, yet continued to experience pain and bleeding.
  • - Further imaging revealed a hematoma in the psoas muscle, and blood tests confirmed the diagnosis of acquired hemophilia A, highlighting an unusual case of this disease linked to gastrointestinal bleeding.
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  • - Pluripotent stem cell transplantation is a potential treatment for hard-to-treat diseases, but finding suitable donor stem cells that match human leukocyte antigens (HLA) is very challenging due to HLA diversity.
  • - Traditional methods to create HLA-matched stem cells are time-consuming, leading researchers to explore HLA engineering as a faster, more cost-effective alternative to prevent immune rejection in transplants.
  • - In this study, CRISPR/Cas9 technology was used to knock out HLA-B in induced pluripotent stem cells (iPSCs), resulting in these cells showing reduced immunogenicity, thus supporting the idea that HLA-engineered iPSCs could be viable for stem cell transplantation
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Background: Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). The drug is cost-effective, but sometimes causes hepatotoxicity, requiring a physician's attention. In this study, we simulated hepatotoxicity by treating hepatocytes derived from RA patient-derived induced pluripotent stem cells (RA-iPSCs) with MTX.

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Article Synopsis
  • Sodium chloride (NaCl) may play a role in autoimmune diseases by increasing the production of pathogenic CD4 T helper cells that produce interleukin-17 (Th17 cells), particularly in arthritis cases.* -
  • In a study involving mice with collagen-induced arthritis (CIA) and human patients, a high-salt diet led to more severe arthritis symptoms and higher levels of Th17 cells, alongside increased IL-17 in affected tissues.* -
  • The findings suggest that reducing salt intake may be a beneficial strategy for managing inflammatory arthritis conditions like rheumatoid arthritis (RA).*
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