Publications by authors named "Risa Okada"

Article Synopsis
  • Long-duration spaceflight can stress the skeletal and immune systems, but the specific response mechanisms are still not fully understood.
  • A study with mice on the ISS evaluated how different gravitational conditions (microgravity, lunar gravity, and Earth gravity) affected their bone, thymus, and spleen over 25-35 days.
  • Results showed that while bone density loss in microgravity was mostly restored in Earth gravity, lunar gravity only offered partial recovery; microgravity also caused thymus shrinkage, partially reversible by both lunar and Earth gravity but with ongoing gene expression issues.
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Muscle regeneration depends on muscle stem cell (MuSC) activity. Myogenic regulatory factors, including myoblast determination protein 1 (MyoD), regulate the fate transition of MuSCs. However, the direct target of MYOD in the process is not completely clear.

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Background And Aim: Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B.

Methods: A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The was the association between MRE-based liver stiffness and HCC.

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Background And Aim: Immune checkpoint inhibitors pose the risk of immune-related adverse events (irAEs). Recent data suggest that irAEs may be associated with a favorable prognosis. This study aimed to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable hepatocellular carcinoma.

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Aim: A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population.

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Article Synopsis
  • Spaceflight can lead to health issues, affecting various systems like the immune system, with oxidative stress playing a key role.
  • Research on Nrf2-knockout mice showed they experienced worse immunosuppression and inflammation from spaceflight compared to normal mice.
  • The findings suggest that enhancing Nrf2 activity could help alleviate health challenges faced by astronauts during space travel.
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Skeletal muscle is sensitive to gravitational alterations. We recently developed a multiple artificial-gravity research system (MARS), which can generate gravity ranging from microgravity to Earth gravity (1 g) in space. Using the MARS, we studied the effects of three different gravitational levels (microgravity, lunar gravity [1/6 g], and 1 g) on the skeletal muscle mass and myofiber constitution in mice.

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Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice.

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The vestibular system is known to participate in controlling posture and metabolism. Different gravitational environments, including microgravity or hypergravity, cause plastic alteration of the vestibular system, and plasticity is important for adaptation to a novel gravitational environment. However, it is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading.

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Article Synopsis
  • * Research found that the amount of white fat tissue in mice increases during spaceflight, and this increase is less pronounced in mice that don't have Nrf2 (Nrf2 knockout).
  • * Analyses showed that certain lipid levels in the blood change significantly during and after spaceflight, with Nrf2 knockout mice showing different metabolic responses compared to normal mice, highlighting Nrf2's key role in lipid metabolism under stress.
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Article Synopsis
  • Space travel negatively affects health due to environmental stresses like microgravity and radiation, impacting kidney function, blood pressure, and bone health.
  • A study examined the role of the Nrf2 protein in kidney function in mice after a 31-day mission on the International Space Station, revealing changes in gene expressions related to these bodily functions.
  • Results showed that certain genes, particularly Ugt1a isoforms, were induced in the kidneys post-spaceflight to help excrete excess lipids, highlighting the kidneys' important role in adapting to gravity changes during space travel.
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Purpose: This study aimed to investigate the impact of sarcopenia on activities of daily living (ADL) recovery and hospitalization costs in older patients admitted to convalescent rehabilitation wards.

Methods: This prospective cohort study included 104 patients aged ≥ 65 years who were admitted to convalescent rehabilitation wards. The primary outcome was ADL recovery as evaluated by the Functional Independence Measure (FIM) efficiency during hospitalization, and the secondary outcome was hospital-related costs.

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Microgravity induces skeletal muscle atrophy, particularly in the soleus muscle, which is predominantly composed of slow-twitch myofibre (type I) and is sensitive to disuse. Muscle atrophy is commonly known to be associated with increased production of reactive oxygen species. However, the role of NRF2, a master regulator of antioxidative response, in skeletal muscle plasticity during microgravity-induced atrophy, is not known.

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Spaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS).

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Article Synopsis
  • Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome that resists steroid treatment, often leading to kidney failure, with spontaneous recovery being uncommon.
  • The study reveals that the basic leucine zipper transcription factor, MafB, is crucial for podocyte function and is decreased in patients with FSGS; mice lacking MafB specifically in podocytes developed FSGS and severe proteinuria.
  • Overexpressing MafB in podocytes of transgenic mice was found to reduce adriamycin-induced FSGS symptoms, suggesting MafB as a potential new target for FSGS therapies.
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The glomerular filtration barrier is composed of podocytes, glomerular basement membrane, and endothelial cells. Disruption of these structures causes several glomerular injuries, such as focal segmental glomerulosclerosis (FSGS). The surface of podocyte apical membranes is coated by negatively charged sialic acids on core 1-derived mucin-type O-glycans.

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Article Synopsis
  • The study examined the impact of living in space on male reproductive health by observing mice in both artificial gravity and microgravity environments for 35 days on the ISS.
  • Mice showed a decrease in accessory gland weight, but no significant changes in reproductive organs, sperm functionality, or gene expression were found.
  • Fertilized eggs from mice in both space conditions resulted in similar numbers of healthy pups as those from ground control mice, suggesting short-term space exposure doesn't harm male fertility.
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The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear.

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Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown.

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The core 1 β1,3-galactosyltransferase-specific molecular chaperon (Cosmc) is essential for the synthesis of the core 1 structure of mucin-type O-glycans. To clarify the physiological role of core 1-derived O-glycans in macrophages, we exploited the LysM-Cre transgene to generate a conditional Cosmc mutant allele (conditional Cosmc knockout; cKO) in myeloid cells. cKO mice developed normally with no gross phenotypic abnormalities or abnormal peripheral blood counts.

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The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF.

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The small G protein Arf6 and the GTPase dynamin2 (Dyn2) play key roles in clathrin-mediated endocytosis (CME). However, their functional relationship remains obscure. Here, we show that Arf6 functions as a downstream molecule of Dyn2 in CME.

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Article Synopsis
  • The lipid kinase PIP5K produces a phospholipid called phosphatidylinositol 4,5-bisphosphate, with three identified isozymes in mammals: PIP5K1A, PIP5K1B, and PIP5K1C.
  • This study explores the roles of PIP5K1A and PIP5K1B in spermatogenesis using genetically modified mice, revealing that absence of these isozymes leads to reduced fertility.
  • Findings show that mice lacking both PIP5K1A and PIP5K1B had disorganized F-actin and fewer elongated spermatids, suggesting these isozymes work together to maintain sperm number and proper
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