To investigate the influence of genome editing on the taste and odor of fish meat, we conducted a comparative analysis of taste components, odor components and lipid oxidation index, in the dorsal muscle of mc4r-deficien...To investigate the influence of genome editing on the taste and odor of fish meat, we conducted a comparative analysis of taste components, odor components and lipid oxidation index, in the dorsal muscle of mc4r-deficient red sea bream compared to the unedited control. In terms of taste components, only some free amino acids were significantly difference in the mc4r-deficient group compared with the unedited control group. Differences were also noted in non-protein nitrogen, equivalent umami concentration, and some taste-active value between the mc4r-deficient and unedited control groups. Regarding odor components, some volatile organic compounds were significantly difference in the mc4r-deficient group. However, no differences were observed in other taste and odor components, or the lipid oxidation index between these groups. These findings suggest that the effect of mc4r deficiency on taste and odor-related components and lipid oxidation in red sea bream muscle is minor.
LPS-induced inflammation triggers metabolic reprogramming and nutritional decline. This study aimed to identify biomarkers for inflammatory and nutritional stress using GC-MS/MS-based metabolomic profiling. Male mice rec...LPS-induced inflammation triggers metabolic reprogramming and nutritional decline. This study aimed to identify biomarkers for inflammatory and nutritional stress using GC-MS/MS-based metabolomic profiling. Male mice received LPS to induce systemic inflammation. Evaluations included liver histology (H&E, Gr-1), blood biochemistry, and metabolomic analysis of liver and plasma. LPS administration significantly increased hepatic neutrophil infiltration and liver enzymes, while decreasing nutritional markers (total protein, albumin, LDL-cholesterol). In the liver, LPS increased glycolytic and TCA cycle intermediates (e.g. 3-phosphoglycerate, citric acid) but decreased amino acids, including glutamine and tryptophan. Plasma analysis showed significant decreases in tryptophan, glucose, and succinic acid. Notably, tryptophan was significantly reduced in both compartments. Our findings demonstrate that tryptophan serves as a robust biomarker for monitoring the intersection of inflammatory response and nutritional status, reflecting synchronized metabolic shifts in the liver and plasma.
Periodontal disease is a major oral infectious condition that leads to the degradation of alveolar bone and subsequent tooth loss. Porphyromonas gingivalis, a keystone pathogen in periodontitis, plays a critical role in...Periodontal disease is a major oral infectious condition that leads to the degradation of alveolar bone and subsequent tooth loss. Porphyromonas gingivalis, a keystone pathogen in periodontitis, plays a critical role in disease initiation and progression. In a previous study, we demonstrated the anti-P. gingivalis activity of epimedokoreanin B, a prenylated flavonoid derived from Epimedium species. However, its in vivo efficacy against periodontitis remains unclear. Oral administration of epimedokoreanin B attenuated P. gingivalis-induced alveolar bone resorption in murine periodontitis models and suppressed infection-induced antibody production Furthermore, epimedokoreanin B compromised bacterial membrane integrity and virulent gene expressions. In this preclinical study, in vitro and in vivo analyses indicate that epimedokoreanin B suppressed both bacterial viability and virulence, thereby attenuating alveolar bone loss caused by periodontitis. These findings suggest that epimedokoreanin B is a promising candidate for the development of novel therapeutics targeting periodontal pathogens.
Cacti are xerophytic plants characterized by water-storing cladodes, thick cuticles, and CAM photosynthesis, enabling high productivity under harsh conditions. They accumulate ascorbate (AsA) at levels comparable to thos...Cacti are xerophytic plants characterized by water-storing cladodes, thick cuticles, and CAM photosynthesis, enabling high productivity under harsh conditions. They accumulate ascorbate (AsA) at levels comparable to those of leafy vegetables, potentially contributing to stress tolerance and nutritional value. However, the regulation of AsA accumulation in cacti remains poorly understood. Here, we used the dwarf prickly pear cactus Nopalea cochenillifera to investigate the tissue-specific distribution and environmental responses of AsA. AsA preferentially accumulated in the cortex, exhibited light-dependent increases, and was maintained or even increased under high-light, drought, and low-temperature stress conditions. Supplementation experiments with AsA and its precursors suggest the presence of multiple biosynthetic pathways and inter-cladode transport mechanisms. These results provide insights into mechanisms specific to the cactus N. cochenillifera for maintaining AsA homeostasis under adverse environmental conditions. This study provides the first evidence of tissue-specific and stress-responsive regulation of AsA metabolism in cactus cladodes.
Butyrophilin subfamily 1 member A1 (BTN1A1) is a major protein of the milk fat globule membrane, but its immunoregulatory function remains largely unresolved, despite its structural similarity to the B7 co-stimulatory mo...Butyrophilin subfamily 1 member A1 (BTN1A1) is a major protein of the milk fat globule membrane, but its immunoregulatory function remains largely unresolved, despite its structural similarity to the B7 co-stimulatory molecules. In this study, we investigated the immunological significance of BTN1A1 in gastrointestinal epithelial cells. The human ectodomain of BTN1A1 expressed as a soluble Fc fusion protein (ectoBTN-Fc) was added to HT29-MTX-E12 cells as a model for gastrointestinal epithelial cells. In the absence of TNF-α, it significantly promoted MUC5AC production via a weak activation of NF-κB signal transduction pathway. In contrast, prior incubation with ectoBTN-Fc inhibited TNF-α-provoked-IL-8 secretion by suppressing the phosphorylation of NF-κB p65. Binding analyses demonstrated that ectoBTN-Fc likely binds to HT29-MTX-E12 cells, followed by its endocytosis. These results suggest a dual-faceted regulatory function of BTN1A1. It reinforces intestinal mucosal barrier function under basal conditions, while it may endow a prophylactic effect alleviating strong inflammatory stimulation.
The biosynthetic gene cluster for PF1451A (1), a potent fungicidal peptide, was identified, showing 1 is a member of ribosomally synthesized and post-translationally modified peptides of fungal origin. Notably, a hypothe...The biosynthetic gene cluster for PF1451A (1), a potent fungicidal peptide, was identified, showing 1 is a member of ribosomally synthesized and post-translationally modified peptides of fungal origin. Notably, a hypothetical protein belonging to IPR053008 family was involved in the desaturation of valine residue. Bioinformatic analysis demonstrated wide distribution of similar proteins in the fungal genomes.
Vaspin is an adipokine involved in metabolic regulation; however, the mechanisms governing its transcription in obesity remain unclear. Here, we investigated the role of peroxisome proliferator-activated receptor γ (PPAR...Vaspin is an adipokine involved in metabolic regulation; however, the mechanisms governing its transcription in obesity remain unclear. Here, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) in regulating Vaspin expression in white adipose tissue (WAT). Vaspin expression was markedly reduced in the WAT of obese ob/ob mice and was restored following rosiglitazone treatment. Reporter assays revealed that ligand-activated PPARγ promotes Vaspin transcription through a weak but functional PPAR response element (PPRE). Promoter deletion analysis further showed that this PPRE contributes to transcriptional activation, whereas additional promoter regions containing C/EBP-responsive elements sustain residual transcriptional activity. These findings suggest that Vaspin expression is regulated, at least partly, through a non-canonical PPARγ-dependent mechanism involving cooperative transcriptional regulation. Our findings provide insight into adipokine regulation in obesity and highlight gene-specific differences in PPARγ-mediated transcription.
This study investigated the molecular mechanisms and therapeutic efficacy of chitosan-based thymol gels (2.5%, 5%, and 10%) in postoperative neuropathic pain. Gels exhibited pseudoplastic shear-thinning behavior and a bi...This study investigated the molecular mechanisms and therapeutic efficacy of chitosan-based thymol gels (2.5%, 5%, and 10%) in postoperative neuropathic pain. Gels exhibited pseudoplastic shear-thinning behavior and a biphasic release profile, achieving > 90% cumulative release within 12 h. Using a Wistar rat model of hind paw incision, topical treatment with 5% and 10% thymol gels significantly (p < 0.05) reversed the reduction in paw withdrawal latency and threshold compared to the controls. Thymol gel markedly decreased serum corticosterone, cyclooxygenase-2 (COX-II), and prostaglandin E2 (PGE2) levels. Furthermore, it downregulated the messenger ribonucleic acid (mRNA) expression of interleukins and tumor necrosis factor in the sciatic nerve. Histopathological analysis confirmed reduced inflammation and congestion. Positive correlations were observed between pro-inflammatory cytokine expression and serum corticosterone, PGE2, and COX-II levels. These findings suggest that thymol gel effectively ameliorates anesthesia-related postoperative neuropathic pain by modulating key inflammatory mediators, suggesting its beneficial treatment option for alleviating such pain.
Beer color is primarily formed through the Maillard reaction. Our research focused on identifying low-molecular-weight pigments in beer, which led to the detection of an unidentified pigment (X) with an absorption maximu...Beer color is primarily formed through the Maillard reaction. Our research focused on identifying low-molecular-weight pigments in beer, which led to the detection of an unidentified pigment (X) with an absorption maximum at around 400 nm in the basic fraction of beer samples. We found that the amount of compound X increased more than 30 times when fructose was added to dark beer and subsequently autoclaved. We successfully isolated compound X from 10 L of the heated beer using various chromatographic procedures. The mass spectrometry showed that the molecular formula of compound X is C16H17O4N. The NMR spectrum analyses indicated that compound X is (5-{(E)-[2-(5-hydroxymethylfuran-2-yl)-5,6-dihydropyridin-3(4H)-ylidene]methyl}furan-2-yl)methanol. Since this yellow pigment is a novel Maillard reaction product and a derivative of furpipates, we named it beer-furpipate. Pale and dark beers contain about 0.06 μg/mL and 0.18 μg/mL of this pigment, respectively.
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates the metabolism of exogenous compounds. Pharmacological inhibition of AhR reduces lipid droplet (LD) accumulation and suppresses hepatiti...Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates the metabolism of exogenous compounds. Pharmacological inhibition of AhR reduces lipid droplet (LD) accumulation and suppresses hepatitis C virus (HCV) proliferation. Recent evidence implicates AhR in the propagation of viruses such as herpes simplex virus type 1 (HSV-1), making it a host factor regulating the proliferation of diverse viruses and an attractive target for broad-spectrum antivirals. To identify AhR ligands with antiviral activity, we screened secondary metabolites derived from fungi isolated from various animals. We identified roquefortine C, an indole alkaloid obtained from quail-derived fungi, as an AhR antagonist. Roquefortine C suppressed LD formation and HCV production in human hepatoma cells. Additionally, it showed anti-HSV-1 and anti-pseudorabies virus (PRV) activities. Notably, our study demonstrated the relationship between AhR and PRV for the first time. AhR ligands could represent potential lead compounds with broad-spectrum antiviral properties.
Blueberry leaves (Vaccinium virgatum Aiton), cultivated in Miyazaki Prefecture, Japan, represent a promising natural health-promoting resource. This study investigated the anti-inflammatory effects of blueberry leaf extr...Blueberry leaves (Vaccinium virgatum Aiton), cultivated in Miyazaki Prefecture, Japan, represent a promising natural health-promoting resource. This study investigated the anti-inflammatory effects of blueberry leaf extract (BLEx) using lipopolysaccharide-stimulated RAW264 macrophage cells. BLEx (up to 100 μg/mL) significantly suppressed nitric oxide production and reduced both the secretion and mRNA expression of interleukin (IL)-1β and IL-6, while showing no significant effect on tumor necrosis factor-α, indicating selective anti-inflammatory activity. Highly polymerized proanthocyanidins, one of the major components of BLEx, contributed to the suppression of IL-1β production. BLEx treatment also induced morphological changes, including intracellular vacuole formation, suggesting the involvement of autophagy. Consistently, the expression of autophagy-related factors increased in a concentration-dependent manner, and inhibition of autophagy attenuated the suppressive effect of BLEx on IL-1β. Overall, BLEx exerts anti-inflammatory effects partly via autophagy activation and may be useful for preventing IL-1β-related inflammatory disorders.
While short-term antibiotic exposure has been reported to exacerbate the development of allergies, the effects of long-term administration remain less understood. This study addressed the influences of prolonged antibiot...While short-term antibiotic exposure has been reported to exacerbate the development of allergies, the effects of long-term administration remain less understood. This study addressed the influences of prolonged antibiotic administration in a murine model of food allergy. Mice received a broad-spectrum antibiotic cocktail (ABX) for six weeks from pre-sensitization through allergen challenge. ABX reduced allergic reactions, serum IgE levels, and intestinal mast cell counts. Production of Th2 cytokine, but not of Th1 and Th17 cytokines, was lowered in allergen-stimulated splenocytes of ABX-treated allergic mice, whereas the levels of these cytokines in their intestines decreased. ABX did not significantly alter the levels of regulatory cytokine IL-10 in intestines and regulatory T cells in spleens. ABX reduced gut bacterial amount, though Lactobacillus, Lactococcus, and Streptococcus remained detectable. Collectively, the long-term ABX suppresses allergic reaction by modulating Th2-mediated events dominantly, providing insights into the complex role of antibiotics in allergy models.
Diphenylmethylene serine methyl ester is an important precursor for the synthesis of O-glycoprotein mimics; however, it exists as an equilibrium mixture of imine and oxazolidine forms due to intramolecular cyclization. U...Diphenylmethylene serine methyl ester is an important precursor for the synthesis of O-glycoprotein mimics; however, it exists as an equilibrium mixture of imine and oxazolidine forms due to intramolecular cyclization. Upon crystallization from ether/hexane, the oxazolidine form is typically obtained as the predominant species, and the pure imine form has not been isolated to date. In this study, diphenylmethylene serine methyl ester was synthesized from serine methyl ester and benzophenone imine, purified by chromatography, and subsequently recrystallized from methanol to selectively afford the imine form in high purity. The structure was confirmed by nuclear magnetic resonance spectroscopy and single-crystal X-ray diffraction analysis. Tautomeric interconversion was investigated in deuterated chloroform at various temperatures, revealing a gradual conversion of the imine into the oxazolidine form until equilibrium was established. These findings clarify the tautomeric behavior of this compound and provide an effective strategy for the selective isolation of tautomers of serine derivatives.
The brewer's yeast Saccharomyces pastorianus originated as a hybrid between the mesophilic yeast Saccharomyces cerevisiae and cryotolerant yeast Saccharomyces eubayanus. In this study, we investigated temperature-depende...The brewer's yeast Saccharomyces pastorianus originated as a hybrid between the mesophilic yeast Saccharomyces cerevisiae and cryotolerant yeast Saccharomyces eubayanus. In this study, we investigated temperature-dependent changes in lipid composition in three yeast species using untargeted lipidomics. We found that both S. cerevisiae and S. pastorianus accumulated storage lipids, particularly triacylglycerols (TG), as the temperature decreased, whereas TG levels in S. eubayanus showed slight temperature-dependent changes. Mitochondria-associated lipids, such as cardiolipin (CL) and its precursor phosphatidylglycerol, also exhibited species-specific patterns. In particular, S. cerevisiae and S. eubayanus differed in their regulatory modes of fatty acid desaturation in CL. The acyl chain composition of CL in S. pastorianus was biased toward the characteristics of S. eubayanus. Our findings show that S. pastorianus integrates parental lipid regulatory systems in a lipid class-specific manner, combining S. cerevisiae-like regulation of storage lipids with S. eubayanus-like control of mitochondrial membrane lipids.
Ethanol extracts from four species of green algae were comparatively evaluated for anti-melanogenic activity using B16F10 mouse melanoma cells. The extract derived from Ulva prolifera demonstrated the strongest inhibitor...Ethanol extracts from four species of green algae were comparatively evaluated for anti-melanogenic activity using B16F10 mouse melanoma cells. The extract derived from Ulva prolifera demonstrated the strongest inhibitory effect on melanin synthesis and was thus selected for further investigation to isolate and identify its bioactive constituents. Through sequential chromatographic techniques, two active compounds-1-hexadecatetraenoylglycerol and 1-hexadecatetraenoyl-3-β-D-galactopyranosylglycerol-were isolated and structurally characterized via NMR and mass spectrometric analyses. Notably, hexadecatetraenoic acid alone did not exhibit anti-melanogenic activity under the same experimental conditions, whereas its glycerol-conjugated form, 1-hexadecatetraenoylglycerol, significantly suppressed melanin production. Additionally, neither the ethanol extract of U. prolifera nor the isolated compounds directly inhibited tyrosinase activity, suggesting that they may influence melanogenesis through indirect mechanisms. These results suggest that the molecular configuration of fatty acids plays an important role in anti-melanogenic activity and highlight the potential of lipid components from U. prolifera as functional anti-melanogenic agents.
In this study, beta glucan nanoparticles were fabricated and encapsulated with Doxorubicin for an effective drug delivery for triple negative breast cancer treatment. The synthesized nanoparticles were characterized by F...In this study, beta glucan nanoparticles were fabricated and encapsulated with Doxorubicin for an effective drug delivery for triple negative breast cancer treatment. The synthesized nanoparticles were characterized by FTIR, TEM, SEM, DLS and zeta potential analysis. A drug encapsulation rate of 80% was achieved and drug release studies displayed a better release of drug from encapsulated glucan nanoparticles in acidic media. In vitro cytotoxicity and cellular uptake were evaluated by MTT and fluorescence microscopy, respectively where the IC50 concentrations for Dox and Dox loaded nano glucans were found to be 2.5 and 1µg/ml respectively. SEM, TEM and DLS results showed that beta glucan nanoparticles have a size distribution between 30-100 nm. FTIR and zeta potential analysis confirmed the loading of Dox. The results over MDA-MB-231 cells showed that Dox loaded beta glucan nanoparticles were effectively internalized and had more cytotoxic activity with respect to free drug.
Bifidobacterium psychraerophilum was isolated from Kishu-Narezushi, marking the first discovery of the Bifidobacterium species originating from a spontaneously fermented traditional Japanese food. Kishu-Narezushi is a tr...Bifidobacterium psychraerophilum was isolated from Kishu-Narezushi, marking the first discovery of the Bifidobacterium species originating from a spontaneously fermented traditional Japanese food. Kishu-Narezushi is a traditional Japanese spontaneously fermented food composed of fish, rice, and salt. Typically, Bifidobacterium species are isolated from milk-related fermented foods or human intestines. The isolated strain was identified as B. psychraerophilum and named the Yasuke strain. B. psychraerophilum are closely related with Bifidobacterium aquikeferi and Bifidobacterium crudilactis. The Yasuke strain and Bifidobacterium psychraerophilum DSM 22366 exhibited greater resistant to salt and oxygen compared to other Bifidobacterium species. Draft genome analysis of the Yasuke strain and four other B. psychraerophilum strains indicates the presence of stress tolerance-related genes. Superoxide dismutase [Mn] and glutathione peroxidase genes are observed in this species. Genes involved in phage interactions, proline metabolism, and sugar and amino acid transport were uniquely identified in the Yasuke strain.
Intracellular biosynthesis of natural products in human cells represents a promising strategy for functional drug delivery. Here, we engineered the production of fumagillin metabolites in human cells expressing fungal cy...Intracellular biosynthesis of natural products in human cells represents a promising strategy for functional drug delivery. Here, we engineered the production of fumagillin metabolites in human cells expressing fungal cytochrome P450 Fma-P450. In endothelial-derived EA.hy926 cells, metabolic flux optimization enhanced metabolite production and enabled detection of cytotoxic activity.
For nearly 40 years, from my student days to the present, I have been engaged in research primarily at my alma mater, Nagoya University; at the National Institutes of Health (N.I.H.) in the United States, where I served...For nearly 40 years, from my student days to the present, I have been engaged in research primarily at my alma mater, Nagoya University; at the National Institutes of Health (N.I.H.) in the United States, where I served as a postdoctoral fellow; and at the University of Tokyo, where I am currently affiliated. At each of these institutions, I have consistently focused on research themes related to the chemical reactions underlying biological phenomena associated with food and health, with a particular emphasis on covalent protein modifications induced by reactive species. This research has become the lifelong theme to which I have dedicated my career.
Mitochondrial NADPH is synthesized by isocitrate dehydrogenase (Idp1) from NADP+ and NAD kinase (Pos5) from NADH. Coenzyme Q levels in Schizosaccharomyces pombe were decreased by deletion of idp1 and further lowered by d...Mitochondrial NADPH is synthesized by isocitrate dehydrogenase (Idp1) from NADP+ and NAD kinase (Pos5) from NADH. Coenzyme Q levels in Schizosaccharomyces pombe were decreased by deletion of idp1 and further lowered by deletion of pos5. The NADP+/NADPH ratio of the ∆idp1 strain shifted to an oxidized state. The mitochondrial NADPH pool and its redox state are critical for CoQ biosynthesis.