Publications by authors named "Shinya Oki"

Aim: To evaluate the safety and efficacy of scalp cooling in preventing chemotherapy-induced alopecia among Japanese patients with gynecological cancer.

Methods: A retrospective study was conducted involving 16 patients with gynecological cancer who underwent chemotherapy with scalp cooling at our institution between January 2021 and April 2024. The completion rate of the planned regimens, the success rate (defined as hair loss ≤50%), hair volume recovery 8-12 weeks after chemotherapy, and adverse events were assessed.

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In the ventricular-subventricular-zone (V-SVZ) of the postnatal mammalian brain, immature neurons (neuroblasts) are generated from neural stem cells throughout their lifetime. These V-SVZ-derived neuroblasts normally migrate to the olfactory bulb through the rostral migratory stream, differentiate into interneurons, and are integrated into the preexisting olfactory circuit. When the brain is injured, some neuroblasts initiate migration toward the lesion and attempt to repair the damaged neuronal circuitry, but their low regeneration efficiency prevents functional recovery.

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  • Viral RNA synthesis of mononegaviruses, like the mumps virus (MuV), occurs in specialized cytoplasmic regions called inclusion bodies (IBs) that have liquid-like properties due to liquid-liquid phase separation.
  • Research findings show that MuV IBs have a cage-like structure formed by viral proteins and the viral polymerase that spatially aligns with viral RNAs.
  • The analysis also revealed that host RNAs with G-quadruplex motifs (G4-RNAs) are concentrated in MuV IBs, and these G4-RNAs enhance the formation of these structures by interacting with a specific viral protein.
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Patatin-like phospholipase domain-containing lipase 8 (PNPLA8), one of the calcium-independent phospholipase A2 enzymes, is involved in various physiological processes through the maintenance of membrane phospholipids. Biallelic variants in PNPLA8 have been associated with a range of paediatric neurodegenerative disorders. However, the phenotypic spectrum, genotype-phenotype correlations and the underlying mechanisms are poorly understood.

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  • Cervical conization is a common treatment for cervical intraepithelial neoplasia (CIN) 2/3, but Ho:YAG laser ablation may be a more effective alternative, which this study aimed to explore.
  • The study analyzed data from 607 patients who underwent the Ho:YAG laser treatment from June 2012 to November 2021, reporting a 5.6% recurrence rate of CIN2 or higher after two years.
  • Age was identified as a significant risk factor for recurrence, while preoperative CIN grade and HPV status did not have a major impact; the postoperative high-risk HPV test proved highly effective for detecting recurrences.
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ChIP-Atlas (https://chip-atlas.org/) presents a suite of data-mining tools for analyzing epigenomic landscapes, powered by the comprehensive integration of over 376 000 public ChIP-seq, ATAC-seq, DNase-seq and Bisulfite-seq experiments from six representative model organisms. To unravel the intricacies of chromatin architecture that mediates the regulome-initiated generation of transcriptional and phenotypic diversity within cells, we report ChIP-Atlas 3.

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Mitochondrial and lysosomal functions are intimately linked and are critical for cellular homeostasis, as evidenced by the fact that cellular senescence, aging, and multiple prominent diseases are associated with concomitant dysfunction of both organelles. However, it is not well understood how the two important organelles are regulated. Transcription factor EB (TFEB) is the master regulator of lysosomal function and is also implicated in regulating mitochondrial function; however, the mechanism underlying the maintenance of both organelles remains to be fully elucidated.

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Background: Despite well-documented effects on human health, the action modes of environmental pollutants are incompletely understood. Although transcriptome-based approaches are widely used to predict associations between chemicals and disorders, the molecular cues regulating pollutant-derived gene expression changes remain unclear. Therefore, we developed a data-mining approach, termed "DAR-ChIPEA," to identify transcription factors (TFs) playing pivotal roles in the action modes of pollutants.

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Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.

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Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF.

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  • SETD8 is a histone methyltransferase linked to endometrial cancer, influencing cell proliferation and apoptosis by modifying histone H4 at lysine 20 and affecting the p53 signaling pathway.
  • The study found that SETD8 expression is significantly higher in endometrial cancer tissues and that reducing SETD8 through siRNAs or inhibitors suppresses cancer cell growth and encourages cell death.
  • Key genes related to apoptosis, including KIAA1324 and TP73, were identified as being regulated by SETD8, indicating their importance in cancer progression and prognosis.
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Drugs are expected to recover the cell system away from the impaired state to normalcy through disease treatment. However, the understanding of gene regulatory machinery underlying drug activity or disease pathogenesis is far from complete. Here, we perform large-scale regulome analysis for various diseases in terms of gene regulatory machinery.

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Nucleus-mitochondria crosstalk is essential for cellular and organismal homeostasis. Although anterograde (nucleus-to-mitochondria) pathways have been well characterized, retrograde (mitochondria-to-nucleus) pathways remain to be clarified. Here, we found that mitochondrial dysfunction triggered a retrograde signaling via unique transcriptional and chromatin factors in hepatic cells.

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Natural lipases typically recognize enantiomers of alcohols based on the size differences of substituents near the carbinol moiety and selectively react with the R enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only R enantiomers. We report herein a method for obtaining S enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols by using a well-known R-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety.

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The basic helix-loop-helix transcriptional factor, Bhlhe40 has been shown as a crucial regulator of immune response, tumorigenesis, and circadian rhythms. We identified Bhlhe40 as a possible regulator of osteoclast differentiation and function by shRNA library screening and found that Bhlhe40 was required for osteoclast activation. Bhlhe40 expression was induced in bone marrow macrophages (BMMs) by RANKL, whereas the expression of its homolog Bhlhe41 was decreased in osteoclastogenesis.

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Motivation: Direct reprogramming involves the direct conversion of fully differentiated mature cell types into various other cell types while bypassing an intermediate pluripotent state (e.g. induced pluripotent stem cells).

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Photo-isolation chemistry (PIC) enables isolation of transcriptome information from locally defined areas by photo-irradiation. Here, we present an optimized PIC protocol for formalin-fixed frozen and paraffin mouse sections and fresh-frozen mouse sections. We describe tissue section preparation and permeabilization, followed by reverse transcription using photo-caged primers.

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ChIP-Atlas (https://chip-atlas.org) is a web service providing both GUI- and API-based data-mining tools to reveal the architecture of the transcription regulatory landscape. ChIP-Atlas is powered by comprehensively integrating all data sets from high-throughput ChIP-seq and DNase-seq, a method for profiling chromatin regions accessible to DNase.

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Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here, we identify the transcription factor, MondoA, as a regulator of cellular senescence, autophagy, and mitochondrial homeostasis.

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Background: Elucidating the modes of action (MoAs) of drugs and drug candidate compounds is critical for guiding translation from drug discovery to clinical application. Despite the development of several data-driven approaches for predicting chemical-disease associations, the molecular cues that organize the epigenetic landscape of drug responses remain poorly understood.

Results: With the use of a computational method, we attempted to elucidate the epigenetic landscape of drug responses, in terms of transcription factors (TFs), through large-scale ChIP-seq data analyses.

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Background: Repressor element 1-silencing transcription factor (REST) is a master regulator that is highly expressed in multipotent stem cells to repress gene networks involving a wide range of biological processes. A recent study has suggested that REST might be involved in a misregulation of its target genes in the embryonic brain of offspring derived from aged fathers. However, detailed analyses of the REST function in spermatogenesis are lacking due to difficulty in the detection of REST protein in specific cell types.

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In multicellular organisms, expression profiling in spatially defined regions is crucial to elucidate cell interactions and functions. Here, we establish a transcriptome profiling method coupled with photo-isolation chemistry (PIC) that allows the determination of expression profiles specifically from photo-irradiated regions of interest. PIC uses photo-caged oligodeoxynucleotides for in situ reverse transcription.

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Embryonic stem cells (ESCs) and epiblast-like cells (EpiLCs) recapitulate in vitro the epiblast first cell lineage decision, allowing characterization of the molecular mechanisms underlying pluripotent state transition. Here, we performed a comprehensive and comparative analysis of total glycomes of mouse ESCs and EpiLCs, revealing that overall glycosylation undergoes dramatic changes from early stages of development. Remarkably, we showed for the first time the presence of a developmentally regulated network orchestrating glycosylation changes and identified polycomb repressive complex 2 (PRC2) as a key component involved in this process.

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Advanced paternal age can have deleterious effects on various traits in the next generation. Here, we establish a paternal-aging model in mice to understand the molecular mechanisms of transgenerational epigenetics. Whole-genome target DNA methylome analyses of sperm from aged mice reveal more hypo-methylated genomic regions enriched in REST/NRSF binding motifs.

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Synopsis of recent research by authors named "Shinya Oki"

  • - Shinya Oki's recent research spans the fields of genetics, epigenetics, and cellular biology, focusing on the underlying mechanisms of various diseases, including microcephaly, cancer predisposition, and atrial fibrillation, by analyzing genetic variants and transcription factors.
  • - His work emphasizes the interplay between mitochondrial and lysosomal functions, the role of epigenomic landscapes in understanding how pollutants affect gene expression, and the development of data-mining tools like ChIP-Atlas to explore chromatin architecture and regulatory mechanisms.
  • - Key findings include the identification of pathogenic variants in genes such as BRCA2 and PNPLA8 linked to cancer and neurodegenerative disorders, as well as insights into how cellular stress can activate specific enhancers through retrograde signaling pathways.

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