Publications by authors named "Okuzaki D"

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and GABA, act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.

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Interstitial pneumonia (IP) is a refractory disease that causes severe inflammation and fibrosis in the interstitium of the lungs, often resulting in the development of lung cancer (LC) during treatment. Previous studies have demonstrated that the prognosis of LC complicated by IP is inferior to that of LC without IP. It is therefore of the utmost importance to gain a deeper understanding of the heterogeneity of such tumors.

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Micropapillary adenocarcinoma (MPC) is an aggressive histological subtype of lung adenocarcinoma (LUAD). MPC is composed of small clusters of cancer cells exhibiting inverted polarity. However, the mechanism underlying its formation is poorly understood.

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Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56 NK cells can be expanded , NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB.

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  • Researchers created a new Alzheimer’s disease (AD) model mouse using human tau protein to better understand microglial states related to tau pathology, which hasn't been thoroughly studied yet.
  • The study found that microglia associated with disease increased after tau accumulation, suggesting a shift from age-related microglia to a disease-associated profile in the brains of these model mice.
  • Advanced techniques like single-nucleus RNA sequencing and spatial transcriptomics were employed to highlight how tau propagation affects microglial behavior, paving the way for deeper insights into tau-related changes in the AD brain.
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  • The tumor microenvironment (TME) has immune-suppressive cells, particularly T helper 1-polarized regulatory T cells (T1-T cells), but little is known about their abundance.
  • Research shows that depleting arginase I-expressing tumor-associated macrophages (Arg1 TAMs) can decrease tumor growth and reduce the presence of T1-T cells.
  • Arg1 TAMs produce platelet factor 4 (PF4), which promotes T1-T cell polarization via specific receptors, and targeting PF4 can limit T1-T cell accumulation and aid in fighting tumors.
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The growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre-hypertrophic, and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate.

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Experimental autoimmune encephalomyelitis (EAE) is the most widely used rodent model for multiple sclerosis. Interferon-γ (IFN-γ) and regulatory T cells (Tregs) are individually well known to play beneficial roles in amelioration of EAE. However, little is known about the relationship between IFN-γ and Tregs during the disease.

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Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process.

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One of the dense granule proteins named GRA15 in Toxoplasma gondii (T. gondii), is known to support an innate immune response in host through activation of NF-κB. However, little is known about advantages of GRA15 for parasites.

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The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated.

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  • Circular RNAs (circRNAs) are unique RNA molecules that resist degradation, offering potential as stable biomarkers and therapeutic targets for diseases.
  • This study focused on analyzing circRNAs during the response to the BNT162b2 mRNA vaccine by sequencing blood samples from healthcare workers.
  • A total of 4706 circRNAs were identified, with 4217 being newly expressed during vaccination, suggesting they play a role in immune response and are associated with stress granule assemblies and specific RNA binding proteins.
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Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.

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Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis.

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  • * Neoself-antigens, which are unusual self-targets, are presented on MHC-II when the invariant chain is absent, leading to the activation of autoreactive T cells in SLE.
  • * Research shows that these neoself-reactive T cells expand in SLE patients and can be activated by cells reactivated by the Epstein-Barr virus, indicating a significant relationship between viral infections and the development of lupus.
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We previously demonstrated hepatic, cardiac, and skin inflammation in a high-fat diet-induced steatotic liver disease (SLD) model. However, the molecular mechanism in the kidneys in this model remains unclear. It has been recently reported that SGLT2 inhibitors improve chronic kidney disease (CKD).

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Detecting antibodies, particularly those targeting donor human leukocyte antigens in organ transplantation and self-antigens in autoimmune diseases, is crucial for diagnosis and therapy. Radioprotective 105 (RP105), a Toll-like receptor family protein, is expressed in immune-competent cells, such as B cells. Studies in mice have shown that the anti-mouse RP105 antibody strongly activates B cells and triggers an adjuvant effect against viral infections.

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Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines.

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  • Myasthenia gravis (MG) is connected to thymus abnormalities, but the specific pathologic features in the thymus are not well understood.
  • This study utilized spatial transcriptome analysis to investigate thymoma (tumors of the thymus) and thymic hyperplasia (thymus enlargement) samples, revealing that most thymomas are primarily composed of cortex, while the medullary region is notably enlarged in seropositive cases.
  • The research highlights that the medulla contains unique immune structures and cell types that may be critical to MG pathology, suggesting these regions are important for future understanding and treatment of the disease.
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  • The study compared how patients respond to bacterial sepsis and COVID-19 sepsis by looking at different types of RNA in their blood.
  • Researchers analyzed blood samples from 22 patients with bacterial sepsis, 35 with COVID-19 sepsis, and 15 healthy people to see how their genes were expressed.
  • The results showed important differences in gene activity between the two types of sepsis, which helps scientists understand how these illnesses affect the body differently.
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  • CAR T cell therapy has shown success in treating blood cancers but struggles with solid tumors like non-small cell lung cancer (NSCLC) due to a lack of specific cell surface targets.
  • Researchers identified that CD98 heavy chain protein is overexpressed in NSCLC cells and could serve as a target for CAR T cells.
  • A specific monoclonal antibody called R8H283, which reacts selectively with NSCLC cells without impacting normal tissues, led to the development of CAR T cells that demonstrated significant anti-tumor effects in model studies.
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Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis.

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  • Ahed is a newly identified gene in haematopoiesis that plays a crucial role in blood cell development, discovered through screening mutant embryonic stem cells.
  • Conditional knockout of Ahed leads to severe anemia and prenatal death, as its absence hampers the ability of haematopoietic cells to regenerate in living organisms.
  • Deletion of Ahed disrupts multiple biological pathways in adult mice and is linked to mutations found in cancer patients, highlighting its importance in both normal blood development and potential involvement in cancers.
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  • The liver helps control what comes from the gut, with different zones having unique immune functions.
  • Special immune cells called macrophages in one zone (PV) can reduce inflammation and depend on friendly gut bacteria to work properly.
  • If these macrophages don't function well, it can lead to liver diseases and more inflammation, showing how important they are for keeping the liver healthy.
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