Publications by authors named "Koji Saito"

Perilipin 2 expression is related to poor prognosis of patients with various malignant tumors. It exists on the surface of lipid droplets (LDs), which store lipids that can be used as an energy source during cancer progression. However, the underlying mechanism of lipid metabolism involving LDs in the progression of lung adenocarcinoma is unclear.

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EFA6A is a guanine nucleotide exchange factor for ADP ribosylation factor 6 (Arf6), a small GTPase involved in membrane trafficking and actin cytoskeleton remodeling. While EFA6A-Arf6 signaling has been shown to regulate dendritic spine formation and maintenance in cultured neurons, its role in higher brain functions remains unclear in vivo. Here, we generated mice lacking two EFA6A splicing isoforms, EFA6A and EFA6As, to examine their role in regulating spine morphology and hippocampus-dependent learning and memory.

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Rho family small GTPases are key regulators of the actin cytoskeletal organization that controls cell morphology, but the regulatory mechanism of Rho small GTPase activity is not fully understood. Here we identified septin2, a component of the septin cytoskeleton, as an interacting protein of ARHGAP25, a GTPase-activating protein for Rho small GTPase Rac, in mammalian cells. ARHGAP25 colocalized with septin2 at lamellipodia, which are actin filament-rich protrusions.

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Background/hypothesis: The contraction of the flexor pronator muscles (FPMs) plays an important role in stabilizing the elbow joint in baseball players. However, the influence of different types of contractions on the medial joint space (MJS) in high school baseball players is not well understood. This study aimed to elucidate the effects of individual or combined contractions of the FPMs, specifically the flexor carpi ulnaris, flexor digitorum superficialis (FDS), pronator teres (PT), palmaris longus, and flexor carpi radialis, on the MJS in high school baseball players.

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Iqsec1 (IQ motif and Sec7 domain-containing protein 1), also known as BRAG2 (Brefeldin A-resistant Arf-GEF 2), is a guanine nucleotide exchange factor that regulates membrane trafficking, cytoskeletal organization, and signal transduction by activating class II and III ADP-ribosylation factors. To investigate the physiological role of Iqsec1 at the whole animal level, we generated Iqsec1-deficient mice using CRISPR/Cas9-mediated gene editing. Nearly all Iqsec1 mice (99%) exhibited embryonic lethality with severe growth retardation.

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  • The study investigates a young boy with severe autoimmune conditions who was found to have a germline gain-of-function mutation in the STAT3 gene through whole-exome sequencing.* -
  • Treatment with the targeted therapy tocilizumab led to a reduction in hospital stays and slowed the progression of pulmonary fibrosis, showing promise for managing his condition without increasing steroid use.* -
  • The findings suggest that genetic testing and functional analysis of STAT3 mutations are important for diagnosing early-onset autoimmune diseases and for considering targeted treatment options.*
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Background: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability.

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  • The study aimed to evaluate how well contrast-enhanced computed tomography (CECT) predicts outcomes for patients with severe acute pancreatitis (SAP) by using the computed tomography severity index (CTSI).
  • A retrospective analysis of 1,097 SAP patients from 44 institutions in Japan found that while necrosis in pancreatic tissue increased mortality risks, the overall inflammation did not significantly impact mortality rates.
  • The results showed that the CTSI had a moderate ability (AUC 0.65) to predict mortality, with significant correlations between higher levels of pancreatic necrosis and increased odds of death.
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  • Lipopolysaccharide (LPS) from Gram-negative bacteria activates Toll-like receptors (TLRs) and may affect locomotion in mice when exposed to new environments, with Porphyromonas gingivalis (Pg) LPS's influence being previously unknown.
  • In this study, researchers compared the effects of Pg-LPS and Escherichia coli (Ec-LPS) on mouse locomotion and blood levels of inflammatory markers IL-6, TNF-alpha, and IL-10, using a TLR4 antagonist (TAK-242) to assess TLR4's role.
  • Results showed that while Ec-LPS inhibited locomotion and increased IL-6 and IL-10 levels, Pg-LPS did not produce
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  • The study focuses on kidney podocytes and how their function relies on the actin cytoskeleton regulated by Rho small GTPases, highlighting that podocyte dysfunction is linked to kidney diseases and proteinuria.
  • FilGAP, a protein that activates Rho small GTPase Rac1, is essential for maintaining podocyte structure, as its depletion leads to a loss of actin stress fibers and reduced cell adhesion.
  • The research demonstrates that FilGAP helps podocytes form necessary structures and attachments to the extracellular matrix by inhibiting Rac1 and PAK1 signaling pathways, suggesting its critical role in preventing kidney-related pathologies.
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  • A 63-year-old woman was investigated for superior vena cava syndrome, resulting in the discovery of a tumor in the azygos vein.
  • She underwent video-assisted thoracic surgery to remove the distal end of the vein, followed by complete tumor resection through median sternotomy.
  • Two years post-surgery, the patient remains tumor-free and has no complications or graft occlusions in the reconstructed veins, highlighting the effectiveness of thoracoscopic surgery for such tumors.
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  • A 72-year-old woman had a retroperitoneal tumor found during a CT scan, which was 27 mm in size and located away from major blood vessels; imaging suggested it might be a vascular malformation.
  • The tumor was removed laparoscopically, and further analysis confirmed it was a capillary arteriovenous malformation, highlighting the challenges in diagnosing such cases before surgery.
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The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features.

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Invadopodia are protrusive structures that mediate the extracellular matrix (ECM) degradation required for tumor invasion and metastasis. Rho small GTPases regulate invadopodia formation, but the molecular mechanisms of how Rho small GTPase activities are regulated at the invadopodia remain unclear. Here we have identified FilGAP, a GTPase-activating protein (GAP) for Rac1, as a negative regulator of invadopodia formation in tumor cells.

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  • Granulosa cell tumors (GCTs) are a rare type of ovarian cancer that represent around 2% of ovarian malignancies, often linked to irregular bleeding in postmenopausal women and late recurrences following initial treatment.
  • In a study, two cases of GCTs were examined to explore the role of serum vascular endothelial growth factor (VEGF) levels as a potential biomarker for treatment effectiveness and recurrence risk.
  • The findings suggest that VEGF levels could be clinically significant in monitoring disease progression in GCTs and may help assess the efficacy of treatments like bevacizumab.
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  • COVID-19 can lead to coagulopathy, a condition affecting blood clotting, but the exact mechanisms behind this are still unclear.
  • A study in Japan involving 99 hospitalized COVID-19 patients aimed to investigate the relationship between coagulopathy and extracellular vesicle (EV) levels, focusing on various types of EVs derived from different cell types.
  • The findings revealed that while no significant differences in EV levels were observed between coagulopathy and non-coagulopathy patients, the levels of CD41+ EVs were significantly higher in patients with coagulopathy compared to healthy volunteers, suggesting a potential role for these EVs in the disease's coagulopathy aspect.
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  • This case report details an adult man who experienced spontaneous regeneration of the fibula after a below-the-knee amputation, despite this phenomenon typically occurring in children.
  • The patient had a history of a severe leg injury from a traffic accident, leading to his amputation and subsequent use of a prosthetic limb.
  • Radiographic and pathological examinations showed the regenerated fibula was 7 cm long and composed of normal bone tissue, suggesting that factors like preserved periosteum and negative pressure therapy contributed to the regeneration process.
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  • Cancer-associated fibroblasts (CAFs), specifically stromal spindle cells (SSCs), are linked to aggressive tumor behavior in pulmonary adenocarcinomas, influencing development and metastasis.
  • A study of 211 surgical patients found SSC-positive cases associated with worse clinicopathological features, such as advanced stage and lymph node metastasis.
  • The presence of SSCs in cytological specimens may serve as a crucial indicator for poor prognosis in lung adenocarcinomas, with SSC-positive patients experiencing shorter recurrence-free survival.
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  • A rare anatomical abnormality known as systemic arterial blood supply to a normal lung can lead to pulmonary hypertension, necessitating surgical intervention.* -
  • The report details two cases: one involved a woman in her 50s who underwent a left lower lobectomy with embolization support, and another was a man in his 40s who had a left partial resection with advanced imaging techniques.* -
  • The study emphasizes the safety and effectiveness of combining interventional radiology with thoracoscopic surgery and cone-beam CT imaging to treat this unusual condition.*
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  • Pulmonary capillary hemangiomatosis (PCH) is a rare lung disease marked by abnormal capillary growth in various lung structures, with no known cause.
  • A 38-year-old woman was mistakenly diagnosed with lung carcinoma due to a small nodule, but subsequent surgery revealed that the thickened lung tissue was actually PCH, not cancer.
  • The case highlights the need for more research on PCH, as there are only a few documented instances of solitary PCH lesions.
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Background/aim: Rho small GTPases regulate cancer cell adhesion, migration and invasion through reorganization of the actin cytoskeleton. Rho GTPase Activating Protein 22 (ARHGAP22) is a Rac-specific GAP and suppresses Rac-dependent lamella formation and cell spreading. We have previously shown that ARHGAP22 localizes at endosomes in human melanoma A7 cells.

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Recent comprehensive analyses of mtDNA and orthogonal RNA-sequencing data revealed that in numerous human cancers, mtDNA copy numbers and mtRNA amounts are significantly reduced, followed by low respiratory gene expression. Under such conditions (called mt-Low), cells encounter severe cell proliferation defects; therefore, they must acquire countermeasures against this fatal disadvantage during malignant transformation. This study elucidated a countermeasure against the mt-Low condition-induced antiproliferative effects in hepatocellular carcinoma (HCC) cells.

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  • A young male developed cutaneous IgA vasculitis, hematuria, diarrhea, and pericarditis after his second dose of a COVID-19 mRNA vaccine, showing potential links to autoimmune conditions.
  • Despite treatment with anti-inflammatory medications and prednisolone that improved his symptoms, kidney biopsy indicated only minor glomerular changes and no signs of vasculitis.
  • This case suggests that COVID-19 vaccination could trigger various autoimmune or inflammatory responses, offering insight into the relationship between these disorders.
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  • The COVID-19 pandemic led to a significant shortage of intravenous anesthetics, particularly impacting patients on extracorporeal membrane oxygenation (ECMO).
  • A 52-year-old man with acute respiratory distress syndrome from COVID-19 was treated with ECMO, facing difficulties in managing sedation through traditional IV anesthetics.
  • The medical team successfully used inhaled anesthetics delivered through ECMO to reduce the need for intravenous medications, suggesting a potential solution to the shortage issue.
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