Publications by authors named "Yuki Sugiura"
We developed a single-molecule enzyme activity assay platform for NAD(P)-dependent oxidoreductases, leveraging a new NAD(P)H-responsive fluorogenic probe optimized for microdevice-based fluorometric detection. This platform enabled the detection of enzyme activities in blood and cerebrospinal fluid (CSF), including lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and hexokinases. We demonstrate its potential for activity-based diagnosis by detecting altered populations of enzyme activity species in blood and CSF from liver damage in brain tumor patients.
View Article and Find Full Text PDFPostnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest.
View Article and Find Full Text PDFChemogenetic activation of hepatic G signaling ameliorates hepatic steatosis and obesity.
Biochim Biophys Acta Mol Basis Dis
February 2025
Article Synopsis
- The study investigates the role of G signaling in hepatic steatosis and obesity, highlighting a gap in targeted treatments for nonalcoholic fatty liver disease (NAFLD).
- Mice with liver-specific G-coupled designer GPCR showed that activating G signaling can reduce hepatic steatosis progression and promote fat oxidation, even under high-fat diets.
- The research suggests that G signaling activation has potential therapeutic benefits for preventing liver fat accumulation and obesity, paving the way for future drug development targeting liver GPCRs.
Article Synopsis
- Cellular senescence is a permanent halt in the cell cycle induced by stress, playing roles in aging and tumor suppression.
- The study reveals that DNA damage response (DDR) signaling influences mitochondria to trigger senescence, with a key protein called BNIP3 identified as critical in this process.
- Enhanced fatty acid oxidation (FAO) linked to BNIP3 leads to changes that promote senescence, indicating that targeting mitochondrial metabolism might help control or manipulate cell aging.
Article Synopsis
- Embryo implantation is essential for a healthy pregnancy and is influenced by changes in gene expression and metabolism in the uterus, which respond to hormones and embryo signals.
- Researchers used spatial transcriptomic analysis to identify that lipid metabolism, particularly pathways related to arachidonic acid, is important in the uterus during implantation.
- The study found that the COX2 enzyme plays a crucial role in successful implantation, while the absence of COX1 or COX2 leads to impaired pregnancy or infertility, highlighting the distinct functions of each enzyme in this process.*
Article Synopsis
- Rapid bone regeneration is essential for restoring alveolar bone and oral functions after periodontal diseases, but current biomedical materials fall short.
- Bone autografts aid regeneration but can harm healthy areas, highlighting the need for effective, local treatments, especially for older adults.
- The newly developed COAp-silica block, a bone substitute with a growth factor, shows superior bone regeneration and remodeling compared to existing substitutes, offering a promising advancement in restoring oral function post-periodontal disease.
Article Synopsis
- Researchers studied cold-resistant cells from the Syrian hamster to understand how they survive cold stress, informing therapeutic hypothermia and organ preservation efforts.
- They identified a gene called Gpx4 that prevents cold-induced cell death, showing its crucial role in reducing lipid peroxidation in cold conditions.
- Other pathways that help prevent ferroptosis (a type of cell death) were found to also play a role in protecting hamster cells from cold stress, suggesting potential strategies to enhance cold resistance in human cells.
Article Synopsis
- The study introduces robust design methods for a vertical avalanche photodiode-based CMOS image sensor, focusing on three practical factors: eliminating guard rings for better pixel isolation, ensuring device performance is stable regardless of voltage and temperature changes, and maintaining consistent operation under intense light conditions.
- The design minimizes trade-offs between electric field concentration and pixel isolation, validated through both simulations and experiments, resulting in effective optimization strategies.
- A global feedback resistor is used to stabilize device characteristics, while an in-pixel overflow transistor improves resistance to high illumination; the sensor's robustness is confirmed by extensive testing on multiple chips under extreme conditions for over 1000 hours.
Article Synopsis
- Impaired glucose metabolism in the brain is a key feature of Alzheimer's disease, with recent studies showing that glial cell metabolism is disrupted.
- Inhibition of the enzyme IDO1, which converts tryptophan into kynurenine, can improve memory function in mouse models of Alzheimer's by restoring how astrocytes (a type of brain cell) metabolize.
- IDO1 inhibition not only enhances glucose metabolism in the brain but also boosts the production of lactate, which is beneficial for neurons, suggesting potential for IDO1 inhibitors, originally designed for cancer, to be used in Alzheimer's treatment.
Article Synopsis
- Zirconia ceramics are valued in dentistry for their biocompatibility, strength, and aesthetic similarity to natural teeth, but there's a rising need for incorporating antibacterial properties into dental restorations.
- The study investigated how well two antibacterial agents, cetylpyridinium chloride (CPC) and benzalkonium chloride (BKC), attach to zirconia surfaces with different crystal structures—tetragonal and monoclinic.
- Results showed that monoclinic zirconia adsorbed significantly more CPC and BKC than tetragonal zirconia, and in tetragonal zirconia, increased YO content enhanced the adsorption due to complex formation between rare earth elements and the quaternary amines.
Article Synopsis
- Dietary interventions like caloric restriction lead to 'browning' of white fat, which helps maintain health and extends lifespan, but the exact mechanisms remain unclear.
- Researchers found that caloric restriction in humans lowers cysteine levels in white adipose tissue, indicating this amino acid plays a role in the metabolic benefits of dietary changes.
- In a mouse model lacking cysteine, the absence of this amino acid led to significant weight loss and fat utilization, suggesting that cysteine is critical for metabolic health and that its depletion may trigger beneficial responses like fat browning.
Article Synopsis
- Zirconia is favored for dental crowns and bridges due to its strength and biocompatibility, but it can lead to secondary caries because of margin leakage.
- This study investigates adding silver, known for its antibacterial properties, to zirconia to prevent such caries.
- Silver-doped zirconia was created using the sol-gel method, with effective antibacterial properties found in samples with at least a 0.5% silver content after firing at lower temperatures.*
Article Synopsis
- Some RNAs, including Y RNAs, are cleaved during apoptosis, a process whose biological significance and mechanisms are not fully understood.
- Y RNAs are important non-coding RNAs involved in various cellular functions and are linked to autoimmune diseases due to their connection with known autoantigenic proteins, Ro and La.
- The study found that cleavage of Y RNAs during apoptosis is regulated by the caspase 3 enzyme acting on the protein PTBP1, and disruptions in this process can lead to immune system dysregulation and potentially trigger autoimmune disorders.
Article Synopsis
- Impaired glucose metabolism in the brain is a key feature of Alzheimer's disease (AD), affecting the function of astrocytes, which support neurons.
- Inhibiting the enzyme IDO1 restores memory and neuronal function in preclinical models by enhancing astrocytic glucose metabolism and lactate production.
- Targeting IDO1 could offer new therapeutic strategies for AD, as its inhibition improves neuronal health by supporting glucose metabolism in the presence of amyloid and tau pathology.
Article Synopsis
- Aging affects stem cells, leading to decreased function and impacting tissue health, but hematopoietic stem cells (HSCs) develop a resilience that helps them survive.* -
- Old HSCs shift their metabolism by activating the pentose phosphate pathway, allowing them to resist oxidative stress and operate independently of glycolysis.* -
- The study reveals that old HSCs enhance energy production through mitochondrial changes, aided by increased levels of a specific factor (SDHAF1), improving their survival during stress and addressing age-related blood cell formation issues.*
Article Synopsis
- Metabolic pathways adapt quickly to stress, impacting cell behavior, especially in rare hematopoietic stem cells (HSCs).
- Researchers focused on how key enzymes affect glycolytic metabolism in HSCs under different conditions.
- They identified that the enzyme phosphofructokinase (PFK) plays a crucial role in increasing glycolysis during stress, with its regulation influenced by specific modifications, ultimately affecting HSC proliferation and differentiation.
Article Synopsis
- Mitophagy is crucial for maintaining mitochondrial health and involves both ubiquitin-mediated and receptor-mediated pathways.
- HeLa cells lacking the receptors BNIP3 and NIX completely lose mitophagy, while those lacking other receptors do not.
- The study shows that this loss of mitophagy leads to increased mitochondrial reactive oxygen species (mtROS), activating the Nrf2 antioxidant pathway, making these cells more susceptible to ferroptosis.
Recent in vitro experiments showed that combined treatment with MHY1485, a low-molecular-weight compound, and X-ray irradiation significantly increased apoptosis and senescence in tumor cells, which was associated with oxidative stress, endoplasmic reticulum (ER) stress and p21 stabilization, compared to radiation treatment alone. However, evidence for MHY1485 treatment-mediated suppression of tumor growth in animals is still lacking. Furthermore, it has been shown that ER stress enhances immunogenic cell death (ICD) in tumor cells, as it can exert a favorable influence on the anti-cancer immune system.
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- Super-selective adrenal venous sampling (ssAVS) helps collect blood from specific adrenal veins to diagnose conditions related to aldosterone overproduction.
- A new method was developed using liquid chromatography/mass spectrometry to measure levels of aldosterone and related steroids in patients with different types of adrenal issues (unilateral adenoma vs. bilateral hyperplasia).
- While the study found higher levels of 18-oxocortisol in patients with aldosterone-producing tumors, it concluded that these measurements alone aren't definitive for determining the type of condition due to variability between individuals.
Article Synopsis
- Microbiota composed of fungi and bacteria significantly influences the physiological functions of larvae, though the specific species and their impacts are not well understood.
- The study found that a specific yeast is crucial for larval growth in the early fermentation stages, while a particular bacterium takes over as the primary growth supporter in later stages, needing the coexistence of yeasts and lactic acid bacteria for stability.
- The microbiota enhances larval nutrition and promotes gene activity related to cell growth and metabolism, highlighting the important role of these microbial species during developmental transitions.
Article Synopsis
- Researchers analyzed serum metabolites from 83 patients to find early markers for predicting SARS-CoV-2 infection severity.
- High levels of de-aminated amino acid catabolites, linked to nucleotide synthesis, were identified as potential early indicators of severe disease and correlated with viral load.
- Animal studies showed that amino acid de-amination and nucleotide synthesis led to abnormal cell growth in the lungs, suggesting that early lung tissue changes could indicate future inflammation and disease progression.
Article Synopsis
- Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in NAD biosynthesis that presents a promising target for cancer treatment, particularly in neuroendocrine tumors like lung and prostate cancer.
- Neuroendocrine tumors show a particular vulnerability to NAMPT inhibitors (NAMPTi), which is further enhanced by dietary changes that affect NAD synthesis pathways.
- Circulating nicotinic acid riboside (NAR) can decrease the effectiveness of NAMPT inhibitors, but reducing NAR levels in combination with NAMPTi treatment proves to be effective in killing tumor cells in mouse models.
Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory strains provides implications on pathogenic host responses.
Katherine-Sofia Candray-Medina Yu Nakagama Masamichi Ito Shun Nakagama Evariste Tshibangu-Kabamba Yuki Sugiura
Trop Med Health
December 2023
Article Synopsis
- Chagas disease can result in severe heart issues, and different strains of the parasite Trypanosoma cruzi affect the disease's progression and symptoms.
- Researchers studied the effects of various T. cruzi strains on heart cells (cardiomyocytes) to understand how they impact gene expression related to heart damage.
- Key findings indicate that T. cruzi infection elevates oxidative stress and activates specific biological pathways linked to heart cell growth and death, particularly in cells infected by Colombian/Y strains.
Article Synopsis
- The study explores the use of deep learning methods to classify heart failure (HF) severity in patients with hypertrophic cardiomyopathy (HCM) based on their ECG data.
- Researchers developed a neural network model using data from HCM patients to distinguish between different severities of HF, achieving a weighted average F1 score of 0.745.
- The findings indicate that the model effectively utilizes ECG data, particularly highlighting specific QRS wave patterns, demonstrating potential for improving the assessment of HF severity in clinical settings.