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.
View Article and Find Full Text PDFObjective: 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.
J Gerontol B Psychol Sci Soc Sci
May 2024
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.
View Article and Find Full Text PDFObjective: 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.
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.
View Article and Find Full Text PDFLiquid 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.
View Article and Find Full Text PDFPhosphorylation 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.
View Article and Find Full Text PDFBackground 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.
View Article and Find Full Text PDFOsteoporosis 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.
View Article and Find Full Text PDFOsteogenesis 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.
View Article and Find Full Text PDFGene 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.
View Article and Find Full Text PDFHypoxic 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.
View Article and Find Full Text PDFEarly 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.
View Article and Find Full Text PDFHuman 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.
View Article and Find Full Text PDFBackground: 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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