Publications by authors named "Shinji Kume"

Epidemiological studies suggest that poor nutrition during pregnancy predisposes offspring to the development of lifestyle-related noncommunicable diseases and psychiatric disorders later in life. However, the molecular mechanisms underlying this predisposition are not well understood. In our previous study, using rats as model animals, we showed that behavioral impairments are induced by prenatal undernutrition.

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  • Endothelial cells are important for nutrient transport, and -GlcNAcylation, a process mediated by OGT, helps sense nutrients, although its function in these cells is not well understood.
  • This study focused on the role of -GlcNAcylation using -ECKO mice, which lack specific endothelial -GlcNAcylation, comparing them with control mice on different diets.
  • Results showed that -ECKO mice had lower body weight and impaired lipid absorption, along with changes in intestinal cell structure, indicating that -GlcNAcylation is vital for lipid uptake and may lead to new obesity treatments.
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Objective: Carotid artery stenting (CAS) under flow reversal with dual protection using a proximal balloon and distal filter has been an established procedure for internal carotid artery (ICA) stenosis. This study investigates the effect of external carotid artery (ECA) occlusion on outcomes of CAS and ICA flow under flow reversal.

Methods: We reviewed 231 cases of CAS under flow reversal with ECA occlusion and 32 without.

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  • - Acetate, a short-chain fatty acid produced by gut microbiota, is vital for intestinal health and may influence muscle performance, yet its specific effects during resistance exercise are not fully understood.
  • - A study on mice revealed that antibiotic treatment lowered grip strength and muscle fiber size, while acetate supplementation helped counteract these negative effects, suggesting a protective role for acetate in muscle preservation.
  • - Low-fiber diets and the absence of acetyl-CoA synthase 2 in mice also led to reduced muscle size and lifespan, reinforcing the idea that acetate from gut bacteria is essential for maintaining skeletal muscle health.
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Dietary therapy is crucial for diabetes care with the aim of preventing the onset and progression of diabetes and its complications. The traditional approach to dietary therapy for diabetes has primarily focused on restricting the intake of the three major nutrients and rigorously controlling blood glucose levels. However, advancements in nutritional science have shown that within the three major nutrients - carbohydrates, proteins and lipids - there exist multiple types, each with distinct impacts on type 2 diabetes and its complications, sometimes even showing conflicting effects.

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For the advancement of DKD treatment, identifying unrecognized residual risk factors is essential. We explored the impact of obesity diversity derived from different carbohydrate qualities, with an emphasis on the increasing trend of excessive fructose consumption and its effect on DKD progression. In this study, we utilized db/db mice to establish a novel diabetic model characterized by fructose overconsumption, aiming to uncover the underlying mechanisms of renal damage.

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The prevalence of chronic kidney disease (CKD) is increasing worldwide, making the disease an urgent clinical challenge. Caloric restriction has various anti-aging and organ-protective effects, and unraveling its molecular mechanisms may provide insight into the pathophysiology of CKD. In response to changes in nutritional status, intracellular nutrient signaling pathways show adaptive changes.

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The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many patients with diabetes. However, there is still a negative perception of ketone bodies stemming from ketoacidosis.

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Article Synopsis
  • * There is increasing research indicating that ketone bodies may provide health benefits, particularly in protecting organs as we age and potentially preventing kidney diseases, including diabetic kidney disease (DKD).
  • * While more research is needed, emerging evidence suggests that ketone bodies can ease kidney stress from high sugar levels, reduce inflammation, and slow the progression of kidney diseases.
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Renal artery stenosis-induced chronic renal ischemia is an important cause of renal dysfunction, especially in older adults, and its incidence is currently increasing. To elucidate the mechanisms underlying chronic renal hypoperfusion-induced kidney damage, we developed a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury. This model exhibits decreased renal blood flow and function, atrophy, and parenchymal injury in the coiled kidney, along with compensatory hypertrophy in the non-coiled kidney, without chronic hypertension.

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Transient neurological events (TNEs) occur after bypass surgery in Moyamoya disease (MMD); however, their pathology remains unknown. To elucidate the pathophysiology of TNEs, we investigated their relationship with perioperative superficial temporal artery (STA) blood flow volume, which was evaluated using ultrasonography. Forty-nine patients with MMD, who underwent direct bypass surgery, were included and stratified into TNE and non-TNE groups, respectively.

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Objective: Direct bypass surgery by superficial temporal artery (STA) - middle cerebral artery anastomosis is an established procedure for moyamoya disease (MMD). However, some patients may develop cerebral infarction (CI) due to the watershed shift phenomenon after the surgery. This study sought to investigate the correlation between the postoperative changes of STA flow as well as cerebral blood flow (CBF) and the incidence of CI after direct bypass surgery for MMD.

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Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. -linked -acetylglucosamine (-GlcNAc) modification (-GlcNAcylation), which involves the addition of -acetylglucosamine to proteins by -GlcNAc transferase (Ogt), modulates multiple cellular processes. However, little is known about the role of -GlcNAcylation in adipose tissues during body weight gain due to overnutrition.

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Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role of endogenous ketogenesis in mammalian life span, and the safety and efficacy of the long-term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole-body Hmgcs2 deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3-butanediol, a precursor of β-hydroxybutyrate.

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Aims: This study aimed to evaluate changes in glycemic control and diabetes treatment by age group in Japanese patients with type 2 diabetes.

Methods: The study included the results of approximately 40,000 patients/year using cross-sectional and retrospective analyses from 2012 to 2019.

Results: There was little change in the glycemic control status in all age groups during the study period.

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This study, which included serological and cellular immunity tests, evaluated whether coronavirus disease 2019 (COVID-19) vaccination adequately protected healthcare workers (HCWs) from COVID-19. Serological investigations were conducted among 1600 HCWs (mean ± standard deviation, 7.4 ± 1.

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Objective: Intraoperative spinal angiography via the popliteal artery for patients in the prone position has been reported only twice in 4 patients. This study aimed to clarify the safety precautions to be taken with this technique in a larger patient cohort.

Methods: Seven patients with spinal vascular disorders underwent intraoperative spinal angiography in the prone position via the popliteal artery.

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Lipoprotein lipase (LPL) is an enzyme that catalyzes the hydrolysis of circulating triglyceride and the transport of fatty acids into cells. Its activity is positively regulated by insulin, and insulin resistance is associated with low LPL activity and subsequent hypertriglyceridemia. The involvement of hypertriglyceridemia in chronic kidney disease (CKD) is still under the debate in a clinical setting.

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Ketone bodies, including 3HBA, are endogenous products of fatty acid oxidation, and Hmgcs2 is the first rate-limiting enzyme of ketogenesis. From database analysis and in vivo and in vitro experiments, we found that adipose tissue and adipocytes express Hmgcs2, and that adipocytes produce and secrete 3HBA. Treatment with 3HBA enhanced the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors in adipose tissue in vivo and in adipocytes in vitro, accompanied by reduced ROS levels.

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Objective Evaluating the rate of decline in the estimated glomerular filtration rate (eGFR) may help identify patients with occult chronic kidney disease (CKD). We herein report that eGFR fluctuation complicates the assessment of the rate of decline and propose a long-term eGFR plot analysis as a solution. Methods In 142 patients with persistent eGFR decline in a single hospital, we evaluated the factors influencing the rate of eGFR decline, calculated over the long term (≥3 years) and short term (<3 years) using eGFR plots, taking into account eGFR fluctuation between visits.

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Fabry disease is an inherited lysosomal disorder caused by mutations in the alpha-galactosidase A gene. We herein report a Fabry disease patient with enzyme replacement therapy (ERT)-resistant proteinuria who showed improvement in the estimated glomerular filtration rate (eGFR) decline rate after uric acid (UA)-lowering therapy. The patient was diagnosed with Fabry disease at 36 years old.

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Aims: Identifying the mechanisms that underlie progression from endothelial damage to podocyte damage, which leads to massive proteinuria, is an urgent issue that must be clarified to improve renal outcome in diabetic kidney disease (DKD). We aimed to examine the role of dynamin-related protein 1 (Drp1)-mediated regulation of mitochondrial fission in podocytes in the pathogenesis of massive proteinuria in DKD.

Methods: Diabetes- or albuminuria-associated changes in mitochondrial morphology in podocytes were examined by electron microscopy.

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SGLT2 inhibitors may have a potential to stop the decline of renal function independent of the stage of albuminuria in diabetic kidney disease, and can be a new light in the post-RAS inhibitor era.

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The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy.

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