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1.
Peptides ; 177: 171184, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38432550

RESUMO

It is ideal to ingest bioactive substances from daily foods to stay healthy. Rice is the staple food for almost half of the human population. We found that an orally administered enzymatic digest of rice endosperm protein exhibits antidepressant-like effects in the tail suspension test (TST) using mice. A comprehensive peptide analysis of the digest using liquid chromatography-tandem mass spectrometry was performed, and a tridecapeptide QQFLPEGQSQSQK, detected in the digest, was chemosynthesized. Oral administration of the tridecapeptide exhibited antidepressant-like effects at a low dose comparable to classical antidepressant in the TST. This also exhibited anti-depressant-like effect in the forced swim test. We named it rice endosperm-derived antidepressant-like peptide (REAP). Intriguingly, intraperitoneal administration had no effect. Orally administered REAP(8-13) but not REAP(1-7) exhibited antidepressant-like activity, suggesting that the C-terminal structure is important for the antidepressant-like effect. We confirmed the presence of REAP, corresponding to rice glutelin type B4(130-142) and B5(130-142), in the digest. The effects of REAP were blocked by both dopamine D1 and D2 antagonists. These results suggest that it exerts its antidepressant-like activity through activation of the dopamine system. Taken together, oral administration of a novel tridecapeptide exhibited antidepressant-like effects via the dopamine system. This is the first report of a rice-derived peptide that exhibits antidepressant-like effects.

2.
Nutrients ; 15(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37571427

RESUMO

The rice endosperm protein (REP) hydrolysate containing the following rice endosperm protein derived oligopeptides QQFLPEGQSQSQK, LPEGQSQSQK, and pEQFLPEGQSQSQK (a N-terminal pyroglutamate residue-modified peptide) reportedly showed an antidepressant-like effect in an animal model. We investigated the effect of the REP hydrolysate on healthy humans who self-reported mental fatigue with subjectively low vigor. Seventy-six participants (age: 20-64 years) were randomly allocated to two groups. The influence of the REP hydrolysate on the mood state was evaluated in two studies: single intake (Study 1) and repeated intake over 4 weeks (Study 2). A salivary stress marker, Chromogranin A (CgA), was measured in Study 1. The single intake of the REP hydrolysate significantly improved the Profile of Mood Status 2nd edition for adults (POMS 2) subscale of Tension-Anxiety. Additionally, the salivary CgA concentrations were remarkably reduced after the single intake of the REP hydrolysate. Though a single intake of the REP hydrolysate did not significantly influence the other subscales and the TMD of the POMS 2 and the Euthymia Scale, both the subjective and objective results supported the possible effect of the REP hydrolysate on reducing anxiety and nervousness. No significant positive effects on the subjective mood state (Euthymia Scale and POMS 2) and sleep quality (Insomnia Severity Index) were observed in the trial setting employed for Study 2. In conclusion, a single intake of REP hydrolysate might help relax the subjective feelings of tension and anxiety. The effectiveness of repeated REP hydrolysate intake needs to be tested in a different clinical setting.


Assuntos
Oryza , Hidrolisados de Proteína , Adulto , Animais , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Hidrolisados de Proteína/farmacologia , Endosperma , Afeto , Ansiedade , Método Duplo-Cego
3.
J Agric Food Chem ; 71(1): 421-429, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36580688

RESUMO

In this study, we demonstrated that novel rice-derived bioactive peptides promote the secretion of ghrelin, an endogenous orexigenic hormone secreted from the stomach. The enzymatic digest of rice endosperm protein with subtilisin, a microorganism-derived enzyme, stimulated acylated ghrelin secretion in the ghrelin-releasing cell line MGN3-1 and increased food intake after oral administration in mice. By performing a comprehensive analysis based on structure-activity relationships, we selected candidate peptides from over 30,000 peptides in the rice digest. Among them, we found that QAFEPIRSV and TNPWHSPRQGSF, corresponding to the amino acid sequence of the rice endoplasmic proteins glutelin A1 or A2(52-60) and B1 or B2(31-42), respectively, stimulated acylated ghrelin release in MGN3-1 cells. We named them rice-ghretropins A and B. Pyroglutamate formation of rice-ghretropin A, [pyr1]-rice-ghretropin A, also promoted ghrelin secretion. Furthermore, oral administration of rice-ghretropins increased food intake, plasma ghrelin concentration, and small intestinal transit in mice. In addition, the subtilisin digest of the rice protein significantly increased food intake for 4 h in 9 month-old (control: 0.61 ± 0.049 g; digest: 0.83 ± 0.059 g) and 24 month-old mice (control: 0.52 ± 0.067 g; digest: 1.01 ± 0.064 g). In summary, we found that novel bioactive peptides, namely, rice-ghretropins, from the enzymatic digest of rice endosperm stimulated acylated ghrelin secretion and increased food intake. This is the first report of rice-derived exogenous bioactive peptides that increase acylated ghrelin secretion.


Assuntos
Grelina , Oryza , Camundongos , Animais , Grelina/metabolismo , Oryza/metabolismo , Ingestão de Alimentos , Proteínas , Subtilisinas
4.
BMC Plant Biol ; 21(1): 476, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666675

RESUMO

Bacterial canker of tomato (Solanum lycopersicon) caused by the Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) is an economically important disease. To understand the host defense response to Cmm infection, transcriptome sequences in tomato cotyledons were analyzed by RNA-seq. Overall, 1788 and 540 genes were upregulated and downregulated upon infection, respectively. Gene Ontology enrichment analysis revealed that genes involved in the defense response, phosphorylation, and hormone signaling were over-represented by the infection. Induced expression of defense-associated genes suggested that the tomato response to Cmm showed similarities to common plant disease responses. After infection, many resistance gene analogs (RGAs) were transcriptionally upregulated, including the expressions of some receptor-like kinases (RLKs) involved in pattern-triggered immunity. The expressions of WRKYs, NACs, HSFs, and CBP60s encoding transcription factors (TFs) reported to regulate defense-associated genes were induced after infection with Cmm. Tomato genes orthologous to Arabidopsis EDS1, EDS5/SID1, and PAD4/EDS9, which are causal genes of salicylic acid (SA)-deficient mutants, were upregulated after infection with Cmm. Furthermore, Cmm infection drastically stimulated SA accumulation in tomato cotyledons. Genes involved in the phenylalanine ammonia lyase pathway were upregulated, whereas metabolic enzyme gene expression in the isochorismate synthase pathway remained unchanged. Exogenously applied SA suppressed bacterial growth and induced the expression of WRKYs, suggesting that some Cmm-responsive genes are regulated by SA signaling, and SA signaling activation should improve tomato immunity against Cmm.


Assuntos
Interações Hospedeiro-Patógeno , Doenças das Plantas/imunologia , Ácido Salicílico/metabolismo , Solanum lycopersicum/genética , Transcriptoma , Clavibacter/crescimento & desenvolvimento , Clavibacter/fisiologia , Cotilédone/genética , Cotilédone/microbiologia , Cotilédone/fisiologia , Perfilação da Expressão Gênica , Solanum lycopersicum/microbiologia , Solanum lycopersicum/fisiologia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Regulação para Cima
5.
Front Plant Sci ; 12: 647599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447395

RESUMO

The common fig (Ficus carica L.) has a gynodioecious breeding system, and its sex phenotype is an important trait for breeding because only female plant fruits are edible. During breeding to select for female plants, we analyzed the FcRAN1 genotype, which is strongly associated with the sex phenotype. In 12 F1 populations derived from 13 cross combinations, the FcRAN1 genotype segregation ratio was 1:1, whereas the M119-226 × H238-107 hybridization resulted in an extremely male-biased segregation ratio (178:7 = male:female). This finding suggests that the segregation distortion was caused by some genetic factor(s). A whole-genome resequencing of breeding parents (paternal and maternal lines) identified 9,061 high-impact SNPs in the parents. A genome-wide linkage analysis exploring the gene(s) responsible for the distortion revealed 194 high-impact SNPs specific to Caprifig6085 (i.e., seed parent ancestor) and 215 high-impact SNPs specific to H238-107 (i.e., pollen parent) in 201 annotated genes. A comparison between the annotated genes and the genes required for normal embryo or gametophyte development and function identified several candidate genes possibly responsible for the segregation distortion. This is the first report describing segregation distortion in F. carica.

6.
Artigo em Japonês | MEDLINE | ID: mdl-34421069

RESUMO

PURPOSE: In our proton beam therapy center, we use imaging plates (IP) for dose verification of field matching in irradiation (called patch-field technique). In this study, a polymer gel dosimeter, which can perform three- dimensional dose distribution measurement, was used as a new tool for the verification of the patch field irradiation method corresponding to the rectangular irradiation. METHOD: The results of measurements of the PAGAT gel dosimeter to irradiate to two rectangular fields called as patch irradiation fields, which were created using the treatment planning system, were evaluated and compared to the results of IP and plan in profiles near the boundary of two fields. RESULT: In the case of no gap between the two fields, the relative dose using the gel dosimeter was 10.1% higher compared to that measured with the IP in the midpoint of two fields. In case of overlap (called hot region), the result of gels was 6.3% higher than that of IP. In the case of space (called cold region), the result of gels was 14.9% higher than that of IP. The results of the difference between gel and plan in the midpoint of two fields were 14.2% (no gap), -5.0% (hot), and 10.5% (cold). CONCLUSION: We found that the gel dosimeter was a 3-D dosimetric tool and possibility method for dose verification of patch fields. In this study, the results were preliminary and included several error factors. In the future, it is necessary to develop a dosimeter with improved and more precise measurements.


Assuntos
Terapia com Prótons , Géis , Polímeros , Dosímetros de Radiação , Radiometria
7.
BMC Med Educ ; 21(1): 316, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088308

RESUMO

BACKGROUND: Empathy, which involves understanding another person's experiences and concerns, is an important component for developing physicians' overall competence. This longitudinal study was designed to test the hypothesis that medical students' empathy can be enhanced and sustained by Humanitude Care Methodology, which focuses on perception, emotion and speech. METHODS: This six-year longitudinal observational study examined 115 students who entered Okayama University Medical School in 2013. The study participants were exposed to two empathy-enhancing programs: (1) a communication skills training program (involving medical interviews) and (2) a Humanitude training program aimed at enhancing their empathy. They completed the Jefferson Scale of Empathy (JSE) seven times: when they entered medical school, before participation in the first program (medical interview), immediately after the first program, before the second program (Humanitude exercise), immediately after the second program, and in the 5th and 6th year (last year) of medical school. A total of 79 students (69% of the cohort) completed all seven test administrations of the JSE. RESULTS: The mean JSE scores improved significantly after participation in the medical interview program (p < 0.01) and the Humanitude training program (p = 0.001). However, neither program showed a sustained effect. CONCLUSIONS: The Humanitude training program as well as medical interview training program, had significant short-term positive effects for improving empathy among medical students. Additional reinforcements may be necessary for a long-term sustained effect.


Assuntos
Estudantes de Medicina , Empatia , Humanos , Japão , Estudos Longitudinais , Faculdades de Medicina
8.
FEBS Open Bio ; 11(4): 1144-1152, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33605550

RESUMO

Ghrelin is an endogenous orexigenic hormone mainly produced by stomach cells and is reported to influence appetite, gastrointestinal motility and growth hormone secretion. We observed that enzymatic digest of wheat gluten stimulated ghrelin secretion from mouse ghrelinoma 3-1, a ghrelin-releasing cell line. Further on, we characterized the ghrelin-releasing peptides present in the digest by comprehensive peptide analysis using liquid chromatography-mass spectrometry and structure-activity relationship. Among the candidate peptides, we found that SQQQQPVLPQQPSF, LSVTSPQQVSY and YPTSL stimulated ghrelin release. We then named them wheat-ghretropin A, B and C, respectively. In addition, we observed that wheat-ghretropin A increased plasma ghrelin concentration and food intake in mice after oral administration. Thus, we demonstrated that wheat-ghretropin stimulates ghrelin release both in vitro and in vivo. To the best of our knowledge, this is the first report of a wheat-derived exogenous bioactive peptide that stimulates ghrelin secretion.


Assuntos
Grelina/química , Grelina/metabolismo , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/metabolismo , Triticum/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Cromatografia Líquida , Quimotripsina/química , Glutens/química , Hidrólise , Espectrometria de Massas , Camundongos , Camundongos Transgênicos , Proteólise , Relação Estrutura-Atividade
9.
Metabolomics ; 16(5): 63, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32335721

RESUMO

INTRODUCTION: Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential. OBJECTIVE: The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans. METHODS: We performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis. RESULTS: About 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles. CONCLUSION: The results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM.


Assuntos
Medicamentos de Ervas Chinesas/metabolismo , Metabolômica , Extratos Vegetais/metabolismo , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Humanos , Masculino , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Ratos , Ratos Sprague-Dawley
10.
Plant J ; 100(3): 505-521, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31364191

RESUMO

Lysine decarboxylase converts l-lysine to cadaverine as a branching point for the biosynthesis of plant Lys-derived alkaloids. Although cadaverine contributes towards the biosynthesis of Lys-derived alkaloids, its catabolism, including metabolic intermediates and the enzymes involved, is not known. Here, we generated transgenic Arabidopsis lines by expressing an exogenous lysine/ornithine decarboxylase gene from Lupinus angustifolius (La-L/ODC) and identified cadaverine-derived metabolites as the products of the emerged biosynthetic pathway. Through untargeted metabolic profiling, we observed the upregulation of polyamine metabolism, phenylpropanoid biosynthesis and the biosynthesis of several Lys-derived alkaloids in the transgenic lines. Moreover, we found several cadaverine-derived metabolites specifically detected in the transgenic lines compared with the non-transformed control. Among these, three specific metabolites were identified and confirmed as 5-aminopentanal, 5-aminopentanoate and δ-valerolactam. Cadaverine catabolism in a representative transgenic line (DC29) was traced by feeding stable isotope-labeled [α-15 N]- or [ε-15 N]-l-lysine. Our results show similar 15 N incorporation ratios from both isotopomers for the specific metabolite features identified, indicating that these metabolites were synthesized via the symmetric structure of cadaverine. We propose biosynthetic pathways for the metabolites on the basis of metabolite chemistry and enzymes known or identified through catalyzing specific biochemical reactions in this study. Our study shows that this pool of enzymes with promiscuous activities is the driving force for metabolite diversification in plants. Thus, this study not only provides valuable information for understanding the catabolic mechanism of cadaverine but also demonstrates that cadaverine accumulation is one of the factors to expand plant chemodiversity, which may lead to the emergence of Lys-derived alkaloid biosynthesis.


Assuntos
Arabidopsis/metabolismo , Cadaverina/metabolismo , Carboxiliases/metabolismo , Lupinus/enzimologia , Metaboloma , Nitrogênio/metabolismo , Alcaloides/metabolismo , Arabidopsis/genética , Vias Biossintéticas , Carboxiliases/genética , Expressão Gênica , Lupinus/genética , Lisina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Transgenes
11.
Med Teach ; 41(2): 195-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29683011

RESUMO

BACKGROUND: Empathy is an important component of overall clinical competence; thus, enhancing empathy in medical education is essential for quality patient care. AIM: This longitudinal study was designed to address the following questions: 1. Can a targeted educational program in communication skills training enhance empathy in medical students? and 2. Can such a program have a sustained effect? METHODS: Study participants included 116 students who entered Okayama University Medical School in 2011. Students participated in a communication skills training program aimed to enhance their empathy, and completed the Jefferson Scale of Empathy (JSE) five times: at the beginning of medical school, prior to participation in the program, immediately after the program, and in last years of medical school. A total of 69 students, representing 59% of the cohort, completed the JSE in all five test administrations. RESULTS: Students' total scores on the JSE and its two factors (Perspective Taking and Compassionate Care) increased significantly (p < 0.001) after participation in the communication skills training program. However, the program did not have a sustained effect. CONCLUSIONS: Targeted educational programs to enhance empathy in medical students can have a significant effect; however, additional reinforcements may be needed for a sustained effect.


Assuntos
Comunicação , Educação Médica/organização & administração , Empatia , Estudantes de Medicina/psicologia , Competência Clínica , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Relações Médico-Paciente
12.
Biochem Biophys Res Commun ; 505(4): 1050-1056, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30314694

RESUMO

Rubisco, an enzyme for photosynthetic carbon dioxide fixation, is a major green leaf protein and known as the most abundant protein on the Earth. We found that Rubisco digested mimicking gastrointestinal enzymatic conditions exhibited anxiolytic-like effects after oral administration in mice. Based on a comprehensive peptide analysis of the digest using nanoLC-Orbitrap-MS and the structure-activity relationship of known anxiolytic-like peptides, we identified SYLPPLTT, SYLPPLT and YHIEPV [termed Rubisco anxiolytic-like peptide (rALP)-1, rALP-1(1-7) and rALP-2, respectively], which exhibited potent anxiolytic-like effects after oral administration. The anxiolytic-like effects of rALP-1/rALP-1(1-7) were blocked by a serotonin 5-HT1A receptor antagonist, whereas rALP-2-induced effects were inhibited by a δ-opioid receptor antagonist. In conclusion, novel Rubisco-derived anxiolytic-like peptides, rALP-1/rALP-1(1-7) and rALP-2, act via independent neural pathways.


Assuntos
Ansiolíticos/análise , Peptídeos/análise , Folhas de Planta/metabolismo , Proteínas de Plantas/análise , Ribulose-Bifosfato Carboxilase/análise , Spinacia oleracea/metabolismo , Administração Oral , Animais , Ansiolíticos/metabolismo , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos , Peptídeos/metabolismo , Peptídeos/farmacologia , Folhas de Planta/química , Proteínas de Plantas/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Spinacia oleracea/química
13.
FASEB J ; 32(2): 568-575, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970253

RESUMO

We found that the orally administered thermolysin digest of ß-conglycinin exhibits antidepressant-like effects in tail suspension and forced swim tests in mice. A comprehensive peptide analysis of the digest using liquid chromatography/mass spectrometry was performed, and LSSTQAQQSY emerged as a candidate antidepressant-like peptide. Orally administered synthetic LSSTQAQQSY exhibited antidepressant-like effects at a dose of 0.3 mg/kg; therefore, we named the decapeptide soy-deprestatin. In contrast, intraperitoneally administered soy-deprestatin was ineffective. We then hypothesized that it acted on the gut, and its signal was transferred to the brain. Indeed, orally administered soy-deprestatin exhibited antidepressant-like activity in sham-treated, but not vagotomized, mice. Oral administration of soy-deprestatin also increased the c-Fos expression in the nucleus of the solitary tract, which receives inputs from the vagus nerve. These results suggested that the antidepressant-like effects were mediated by the vagus nerve. Thermolysin digest- and soy-deprestatin-induced antidepressant-like effects were also blocked by antagonists of serotonin 5-HT1A, dopamine D1, or GABAA receptors. We also clarified the order of receptor activation as 5-HT1A, D1, and GABAA, using selective agonists and antagonists. Taken together, soy-deprestatin may exhibit antidepressant-like effects after oral administration via a novel pathway mediated by 5-HT1A, followed by D1 and GABAA systems. This is the first orally active peptide demonstrating antidepressant-like effects via gut-brain communication.-Mori, Y., Asakura, S., Yamamoto, A., Odagiri, S., Yamada, D., Sekiguchi, M., Wada, K., Sato, M., Kurabayashi, A., Suzuki, H., Kanamoto, R., Ohinata, K. Characterization of soy-deprestatin, a novel orally active decapeptide that exerts antidepressant-like effects via gut-brain communication.


Assuntos
Antidepressivos/farmacologia , Encéfalo/metabolismo , Mucosa Intestinal/metabolismo , Oligopeptídeos/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Proteínas de Soja/farmacologia , Administração Oral , Animais , Antidepressivos/química , Masculino , Camundongos , Oligopeptídeos/química , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de GABA-A/metabolismo , Antagonistas do Receptor 5-HT1 de Serotonina/química , Proteínas de Soja/química
14.
DNA Res ; 24(6): 649-656, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29106502

RESUMO

The DNA extracted from a high-temperature environment in which micro-organisms are living will be a good source for the isolation of thermostable enzymes. Using a metagenomic approach, we aimed to isolate thermostable ß-xylosidases that will be exploited for biofuel production from lignocellulosic biomass. DNA samples obtained from the soil near a spout of a hot spring (70°C, pH7.2) were subjected to sequencing, which generated a total of 84.2 Gbp with 967,925 contigs of >500 bp in length. Similarity search for ß-xylosidase in the contigs revealed the presence of 168 candidate sequences, each of which may have arisen from more than one gene. Individual genes were amplified by PCR using sequence-specific primers. The resultant DNA fragments were cloned and introduced into Escherichia coli BL21 Star(DE3). Consequently, 269 proteins were successfully expressed in the E. coli cells and then examined for ß-xylosidase activity. A total of 82 proteins exhibited ß-xylosidase activity at 50°C, six of which retained the activity even at 90°C. Out of the six, three proteins were originated from a single candidate sequence, AR19M-311. An amino acid sequence comparison suggested the amino acid residues that appeared to be crucial for thermal stability of the enzymes.


Assuntos
Escherichia coli/enzimologia , Fontes Termais/microbiologia , Metagenômica/métodos , Microbiologia do Solo , Xilosidases/genética , Xilosidases/isolamento & purificação , Sequência de Aminoácidos , Substituição de Aminoácidos , DNA Bacteriano/genética , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Fontes Termais/análise , Filogenia , Homologia de Sequência , Xilosidases/metabolismo
15.
FEBS Lett ; 591(14): 2121-2130, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28649756

RESUMO

Ghrelin, an endogenous peptide isolated from the stomach, is known to stimulate food intake after peripheral administration. We found that the enzymatic digest of ß-lactoglobulin decreases ghrelin secretion from the ghrelin-producing cell line MGN3-1. The peptides present in the digest were comprehensively analyzed using the nanoLC-OrbitrapMS. Among them, we identified that the nonapeptide LIVTQTMKG, corresponding to ß-lactoglobulin(1-9), suppresses ghrelin secretion from MGN3-1 cells. We named LIVTQTMKG 'lacto-ghrestatin'. We found that lacto-ghrestatin decreases intracellular cAMP levels and mRNA expression levels of ghrelin production-related genes in MGN3-1 cells. Orally administered lacto-ghrestatin decreases plasma ghrelin levels and food intake in fasted mice. Lacto-ghrestatin is the first food-derived peptide to suppress ghrelin secretion in vitro and in vivo.


Assuntos
Grelina/metabolismo , Lactoglobulinas/química , Leite/química , Fragmentos de Peptídeos/farmacologia , Administração Oral , Sequência de Aminoácidos , Animais , Bovinos , Linhagem Celular , Colforsina/farmacologia , AMP Cíclico/metabolismo , Digestão/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Jejum/sangue , Grelina/sangue , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Lactoglobulinas/metabolismo , Masculino , Camundongos , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/química
16.
Neurochem Int ; 105: 51-57, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28065795

RESUMO

Here we found that the chymotryptic digest of soy ß-conglycinin, a major storage protein, exhibited anxiolytic-like effects in mice. We then searched for anxiolytic-like peptides in the digest. Based on a comprehensive peptide analysis of the chymotryptic digest by high performance liquid chromatograph connected to an LTQ Orbitrap mass spectrometer and the structure-activity relationship of known peptides, we explored anxiolytic-like peptides present in the digest. FLSSTEAQQSY, which corresponds to 323-333 of the ß-conglycinin α subunit [ßCGα(323-333)] emerged as a candidate. Oral administration of synthetic ßCGα(323-333) exhibited anxiolytic-like effects in the elevated plus-maze and open-field test in male mice. Orally administered ßCGα(323-333) exhibited anxiolytic-like effects in sham-operated control mice but not in vagotomized mice. In addition, oral administration of ßCGα(323-333) increased the expression of c-Fos, a marker of neuronal activity, in the nucleus of the solitary tract, which receives inputs from the vagus nerve. These results suggest that the anxiolytic-like effects were mediated by the vagus nerve. The anxiolytic-like effects of ßCGα(323-333) were also blocked by antagonists of the serotonin 5-HT1A, dopamine D1 and GABAA receptors. However ßCGα(323-333) had no affinity for these receptors, suggesting it stimulates the release of endogenous neurotransmitters to activate the receptors. Taken together, a soy-derived undecapeptide, ßCGα(323-333), may exhibit anxiolytic-like effects after oral administration via the vagus nerve and 5-HT1A, D1 and GABAA systems.


Assuntos
Ansiolíticos/administração & dosagem , Antígenos de Plantas/administração & dosagem , Ansiedade/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Globulinas/administração & dosagem , Glycine max , Proteínas de Armazenamento de Sementes/administração & dosagem , Proteínas de Soja/administração & dosagem , Nervo Vago/efeitos dos fármacos , Administração Oral , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Sistema Nervoso Entérico/efeitos dos fármacos , Sistema Nervoso Entérico/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Nervo Vago/metabolismo
17.
Cranio ; 35(1): 38-45, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27077250

RESUMO

OBJECTIVES: This study examined the changes in temporomandibular joint dysfunction (TMD) symptoms and investigated the variations in the disc position, disc and condylar morphology following sagittal split ramus osteotomy (SSRO) with rigid fixation in patients with mandibular prognathism. Furthermore, the authors examined the correlation between mandibular setback and TMD symptoms. METHODS: The study included 24 Japanese patients with jaw deformities who were treated using bilateral SSRO and Le Fort I osteotomy. The clinical and magnetic resonance imaging findings in the temporomandibular joint were evaluated preoperatively and at three and six months postoperatively. RESULTS: The preoperative TMD symptoms were significantly associated with the prevalence of TMD symptoms at six months postoperatively. Anterior disc displacement improved in four joints with slight displacement and with no morphological change. There were no postoperative changes in condylar morphology. There was no significant correlation between mandibular setback and the postoperative TMD symptoms. CONCLUSION: Postoperative TMD symptoms may be influenced mainly by preoperative TMD symptoms rather than mandibular setback using SSRO with rigid fixation. Therefore, patients with TMD symptoms require physical examination and MRI for appropriate diagnosis preoperatively.


Assuntos
Imageamento por Ressonância Magnética/métodos , Mandíbula/fisiopatologia , Osteotomia Sagital do Ramo Mandibular/métodos , Disco da Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adolescente , Adulto , Povo Asiático , Feminino , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Masculino , Má Oclusão Classe III de Angle/complicações , Mandíbula/cirurgia , Côndilo Mandibular/fisiopatologia , Músculos da Mastigação , Pessoa de Meia-Idade , Osteotomia/métodos , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia , Adulto Jovem
18.
J Med Case Rep ; 10(1): 246, 2016 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-27604349

RESUMO

BACKGROUND: Nasoalveolar cysts are rare non-odontogenic cysts that occur beneath the nasal alar region. Few cases of bilateral nasoalveolar cysts have been described. CASE PRESENTATION: We report a rare case of a 67-year-old Japanese woman with bilateral nasoalveolar cysts who presented to our department with the chief complaint of a swollen left nasal alar base. Panoramic radiography revealed no abnormalities. Computed tomography and magnetic resonance imaging revealed a well-circumscribed oval lesion at both alar bases. Therefore, bilateral nasoalveolar cysts were clinically diagnosed. Furthermore, these cysts were extirpated under general anesthesia; the aforementioned diagnosis was histopathologically confirmed. No recurrence has been observed 1 year after surgery. CONCLUSIONS: Nasoalveolar cysts are rare. It is necessary to be careful because nasoalveolar cysts can show bilateral occurrence.


Assuntos
Cistos/diagnóstico por imagem , Cistos/cirurgia , Sulco Nasogeniano/diagnóstico por imagem , Sulco Nasogeniano/cirurgia , Dermatopatias/diagnóstico por imagem , Dermatopatias/cirurgia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Nariz , Tomografia Computadorizada por Raios X
19.
J Biomed Mater Res B Appl Biomater ; 104(7): 1282-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26100641

RESUMO

The aims of this study were to evaluate in vivo the biological responses to implants composed of biodegradable anodized WE43 (containing magnesium yttrium, rare earth elements and zirconium; Elektron SynerMag®) magnesium alloy, monolithic WE43 magnesium alloy and poly-l-lactic acid (PLLA), which are commonly used materials in clinic settings, and to evaluate the effectiveness of the materials as bone screws. The effectiveness of the magnesium alloy implants in osteosynthesis was evaluated using a bone fracture model involving the tibia of beagle dogs. For the monolithic WE43 implants, radiological, and histological evaluation revealed that bone trabeculae around the implanted monolithic WE43 decreased because of an inflammatory response. However, there was no damage due to hydrogen gas or inflammatory response in the bone tissue around the anodized WE43 implants. After 4 weeks, all the PLLA implants (n = 3) had broken but the WE43 implants had not (n = 6). These results suggest that the WE43 implants had sufficient strength to fix bone fractures at load-bearing sites in orthopedic and oral maxillofacial surgery. Therefore, these biodegradable magnesium alloys are good candidates for replacing biodegradable polymers. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1282-1289, 2016.


Assuntos
Implantes Absorvíveis , Ligas , Parafusos Ósseos , Fraturas Ósseas , Magnésio , Poliésteres , Ligas/química , Ligas/farmacologia , Animais , Modelos Animais de Doenças , Cães , Fraturas Ósseas/metabolismo , Fraturas Ósseas/patologia , Fraturas Ósseas/cirurgia , Magnésio/química , Magnésio/farmacologia , Poliésteres/química , Poliésteres/farmacologia
20.
Nat Prod Commun ; 10(3): 499-501, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25924538

RESUMO

Two new isoflavanones, eryvarins Y (1) and Z (2), together with three known compounds (3-5) were isolated from the roots of Erythrina variegata. The structures of 1 and.2 were established on the basis of spectroscopic data. The new compounds are peculiar isoflavanones, possessing both a 3-methylbut-2-en- 1-yl group and a 2-hydroxy-3-methylbut-3-en-1-yl group. Among the isolates, orientanol E (5) exhibited potent antibacterial activity against methicillin- resistant Staphylococcus aureus (MRSA) strains.


Assuntos
Erythrina/química , Isoflavonas/química , Raízes de Plantas/química , Antibacterianos/farmacologia , Isoflavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular
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