Publications by authors named "Tomono Y"

Article Synopsis
  • The study focuses on Laminin 511 (LM511) and its fragment, 511E8, which is thought to enhance cell adhesion and behavior in human skin cells during culture.
  • Researchers examined the effects of 511E8 on reconstituted skin equivalents (SEs) formed from human foreskin keratinocytes and fibroblasts, comparing results from cultures with and without the 511E8 addition.
  • The findings showed that 511E8 improved the formation and continuity of basement membrane-like structures and increased the expression of key collagen genes, indicating its potential benefits in skin cell culture applications.
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Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.

Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.

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  • Epidural and subdural hematomas often occur due to traumatic brain injuries, and while surgery is the main treatment, it's important to prevent complications like post-traumatic epilepsy.* -
  • In a study with rats, researchers found that a monoclonal antibody targeting high mobility group box-1 (HMGB1) effectively reduced inflammation and the release of inflammatory markers after a hematoma occurred.* -
  • The study suggests that using anti-HMGB1 therapy could help minimize brain inflammation and protect neural tissue, making it a potential addition to treatment protocols for epidural hematomas.*
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  • * A recent study explored the implications of a specific mutation (c.1771G>A, p.Gly591Ser) in COL4A6, which is associated with hearing loss and cochlear malformation, by examining Col4a6 knockout (KO) mice.
  • * Results revealed that Col4a6 KO mice had normal hearing thresholds and cochlear structures, suggesting that the harmful effects seen in humans with the COL4A6 mutation are likely due to the
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Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5-fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer.

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Objective: Asymptomatic intracranial dural arteriovenous fistula (DAVF) is a rare disease that is often undiagnosed before symptom onset. The present study aimed to examine the detection rate and radiological features of asymptomatic intracranial DAVF using brain MRI data obtained from the Japanese brain check-up system.

Methods: We retrospectively identified 11745 individuals who underwent brain MRI between January 2010 and December 2014.

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  • The study presents a histochemical technique called vessel painting that enables 3D, multicolor imaging of blood vessels and surrounding tissues, which is crucial for understanding vascular diseases.* -
  • The research includes developing applications that combine vessel painting with immunostaining and tissue clearing for use in advanced microscopy methods, enhancing the imaging capability.* -
  • A new microscopy setup with an aberration correction system was introduced, improving image quality and demonstrating the method's effectiveness by visualizing detailed changes in kidney structures of mice with a specific kidney disease.*
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Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation.

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The basement membrane (BM) is composed of various extracellular molecules and regulates tissue regeneration and maintenance. Here, we demonstrate that collagen XVIII was spatiotemporally expressed in the BM during skin wound healing in a mouse excisional wound-splinting model. Re-epithelialization was detected at days 3 and 6 post-wounding.

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Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as , , , , and , and two human cancer cell lines with similar stem cell gene expression.

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Article Synopsis
  • About 5% of cerebral small vessel diseases are hereditary, often linked to mutations in COL4A1/COL4A2, which lead to weak blood vessels due to impaired collagen secretion.
  • The study aimed to find new genes associated with these disorders by performing whole exome sequencing on two families, revealing biallelic variants in the COLGALT1 gene, which affects collagen modification.
  • Results showed that these variants destabilize protein structure and decrease enzyme activity, confirming that COLGALT1 mutations contribute to similar problems as COL4A1/COL4A2 mutations in causing abnormalities in cerebral blood vessels.
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  • This research investigates the diverse roles of compartmentalized epidermal stem cells in the mouse hair follicle, particularly in forming tactile sensory units.
  • These stem cells express specific genes related to extracellular matrix (ECM) and neurogenesis, and they produce a unique ECM protein called EGFL6, which is essential for the structure and function of mechanosensory complexes.
  • By preserving the original stem cell niche, these epidermal stem cells create stable connections between the hair follicle and the nervous system, maintaining their roles during hair regeneration cycles.
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  • Iron chelation therapy helps treat iron overload disease but can have side effects that complicate cancer treatment, leading to the development of super-polyphenol (SP) as a safer alternative.
  • SP comes in different forms, with water-soluble versions SP6 and SP10 showing the strongest ability to bind iron and potential as anti-cancer agents.
  • In research, SP6 and SP10 were found to effectively inhibit cancer cell growth and tumor growth in models, with minimal toxicity compared to traditional iron chelators.
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  • The study investigates the phosphorylation of type III intermediate filament proteins vimentin, GFAP, and desmin by various kinases, emphasizing its importance for proper cell division.
  • It examines the increased solubility of keratin 5 and keratin 14 (K5/K14) during mitosis and identifies specific phosphorylation sites on K5 that are crucial for effective separation of these filaments.
  • The findings highlight that K5 phosphorylation is primarily regulated by CDK1, Aurora-B, and Rho-kinase, which are essential for the reorganization of the K5/K14 intermediate filament network during cell division.
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Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases.

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Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies.

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Article Synopsis
  • Researchers used suncus (house musk shrew) to create monoclonal antibodies, utilizing their unique immune responses that differ from those of common lab animals like mice and rats.
  • The team injected suncus with antigens to develop plasmacytoma cell lines, leading to the creation of several hybrid cell lines capable of producing specific monoclonal antibodies.
  • The resulting hybrid cells can be cloned and preserved for future use, making them valuable for generating suncus monoclonal antibodies that have not been previously available.
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Objective The correlation of adiponectin with cholesterol concentration of fractionated lipoproteins has not been well investigated. Methods This study included 174 subjects (79 men and 95 women) without diabetes. The medical record data were investigated retrospectively.

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To characterize eplerenone pharmacokinetics (PK) in Japanese chronic heart failure (CHF) patients and to estimate the impact of factors that may affect eplerenone PK, population pharmacokinetic (PPK) analysis was conducted. In addition, PK of Japanese CHF and Western CHF patients from a previous clinical pharmacology study were compared in the analysis. Eplerenone PK was characterized by a 1-compartment PPK model with first-order absorption and lag time in Japanese CHF patients.

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Desmin is a type III intermediate filament (IF) component protein expressed specifically in muscular cells. Desmin is phosphorylated by Aurora-B and Rho-kinase specifically at the cleavage furrow from anaphase to telophase. The disturbance of this phosphorylation results in the formation of unusual long bridge-like IF structures (IF-bridge) between two post-mitotic (daughter) cells.

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Esophageal carcinomas often have a poor prognosis due to early lymph node metastasis. Epithelial-mesenchymal transition (EMT) is strongly associated with the acquisition of cancer metastasis and invasion. However, there is no established treatment to eliminate the EMT of cancer cells.

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Purpose: The aim is to develop a pharmacokinetic model for factor IX activity (FIX) after BeneFIX (nonacog alfa, rFIX) administration and assess potential covariates using all available clinical data collected during development.

Methods: The data set for model development combined observations from eight studies. Postdose FIX observations were adjusted by subtracting predose FIX if these were above the lower limit of quantification (BLQ) and all BLQ observations were removed.

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Background: Few studies have evaluated out-of-office blood pressure (BP) measurements as predictors of coronary artery disease (CAD) events.

Objectives: The aim of this study was to determine morning home blood pressure (HBP) as a predictor of CAD events.

Methods: Using data from the HONEST (Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure) study, we investigated the relationship between morning HBP and incidence of stroke and CAD events.

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ABSTACT Human hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required.

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