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1.
J Infect Dis ; 227(6): 780-787, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36546706

RESUMO

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.


Assuntos
Vacina BNT162 , COVID-19 , Humanos , Afinidade de Anticorpos , Soroterapia para COVID-19 , SARS-CoV-2 , Ureia , Vacinação , Imunoglobulina G , Anticorpos Neutralizantes , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
2.
Biosci Biotechnol Biochem ; 87(11): 1407-1419, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37667506

RESUMO

Although regular exercise has been reported to prevent depression, it has not been clarified whether the gut microbiota is involved in the factors that prevent depression through exercise. We investigated the effects of voluntary exercise on the gut microbiota and the prevention of depression-like behaviors using mice. C57BL/6 J male mice were subjected to 10 weeks of sedentary control or wheel running, then they were subjected to social defeat stress (SDS). Exercise attenuated that sucrose drinking was decreased by SDS treatment. Exercise increased the expression of Bdnf and decreased expression of Zo-1 and Claudin5 in the brain. Fecal Turicibacter, Allobaculum, and Clostridium sensu stricto, and propionate in the cecum were decreased by the exercise. Voluntary exercise-induced antidepressant properties might be partially caused by suppression of serotonin uptake into gut microbiota and increase the permeability of the blood-brain barrier via reduced propionate production.


Assuntos
Microbioma Gastrointestinal , Atividade Motora , Masculino , Camundongos , Animais , Propionatos/farmacologia , Camundongos Endogâmicos C57BL , Antidepressivos/farmacologia , Depressão , Estresse Psicológico
3.
Biosci Biotechnol Biochem ; 86(10): 1423-1430, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-35945649

RESUMO

Fatigue is accompanied by a decrease in physical activity or malaise, and might be reduced by acetyl-L-carnitine (ALC) administration. The purpose of this study was to investigate the preventive effects of ALC on Poly I:C-induced sickness behavior in mice. For the experiment, male C3H/HeN mice were used and treated with ALC for 5 days before Poly I:C administration. ALC administration attenuated the decrease in wheel behavior activity of mice at 24 h after Poly I:C administration and ALC-treated mice quickly recovered from the sickness behavior. The gene expression of brain-derived neurotrophic factor (BDNF) in the cerebrum and hippocampus, which is associated with physical activity, was higher in the ALC-treated group. Translocator protein 18kDa (TSPO), which has cytoprotective effects, was up-regulated in the cerebrum and hippocampus, suggesting that ALC suppressed the decrease in activity induced by Poly I:C treatment through enhancement of cytoprotective effects in the brain.


Assuntos
Acetilcarnitina , Fator Neurotrófico Derivado do Encéfalo , Acetilcarnitina/farmacologia , Acetilcarnitina/uso terapêutico , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Comportamento de Doença , Masculino , Camundongos , Camundongos Endogâmicos C3H , Poli I-C/farmacologia
4.
Neural Comput ; 33(7): 1853-1885, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34411266

RESUMO

Deep neural networks (DNNs) have achieved substantial predictive performance in various speech processing tasks. Particularly, it has been shown that a monaural speech separation task can be successfully solved with a DNN-based method called deep clustering (DC), which uses a DNN to describe the process of assigning a continuous vector to each time-frequency (TF) bin and measure how likely each pair of TF bins is to be dominated by the same speaker. In DC, the DNN is trained so that the embedding vectors for the TF bins dominated by the same speaker are forced to get close to each other. One concern regarding DC is that the embedding process described by a DNN has a black-box structure, which is usually very hard to interpret. The potential weakness owing to the noninterpretable black box structure is that it lacks the flexibility of addressing the mismatch between training and test conditions (caused by reverberation, for instance). To overcome this limitation, in this letter, we propose the concept of explainable deep clustering (X-DC), whose network architecture can be interpreted as a process of fitting learnable spectrogram templates to an input spectrogram followed by Wiener filtering. During training, the elements of the spectrogram templates and their activations are constrained to be nonnegative, which facilitates the sparsity of their values and thus improves interpretability. The main advantage of this framework is that it naturally allows us to incorporate a model adaptation mechanism into the network thanks to its physically interpretable structure. We experimentally show that the proposed X-DC enables us to visualize and understand the clues for the model to determine the embedding vectors while achieving speech separation performance comparable to that of the original DC models.

5.
Transpl Infect Dis ; 23(2): e13496, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33075208

RESUMO

Human adenovirus (HAdV) is an important cause of the common cold and epidemic keratoconjunctivitis in immunocompetent individuals. In immunocompromised patients, HAdV can sometimes cause severe infection such as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated disease, resulting in significant morbidity and also mortality. In particular, severe cases have been reported in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Indeed HAdV has been recognized as a pathogen that requires careful monitoring in allo-HSCT patients. While HAdV hepatitis leading to severe acute liver failure is rare, such liver failure progresses rapidly and is often fatal. Unfortunately, HAdV hepatitis has few characteristic symptoms and physical findings, which makes it difficult to promptly confirm and start treatment. We report here four cases of HAdV hepatitis after allo-HSCT and their autopsy findings.


Assuntos
Infecções por Adenoviridae , Cistite , Transplante de Células-Tronco Hematopoéticas , Falência Hepática Aguda , Infecções por Adenoviridae/terapia , Adenovírus Humanos , Humanos , Falência Hepática Aguda/terapia
6.
J Exp Bot ; 70(18): 4807-4818, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31056658

RESUMO

Decreases in photosynthetic rate, stomatal conductance (gs), and mesophyll conductance (gm) are often observed under elevated CO2 conditions. However, which anatomical and/or physiological factors contribute to the decrease in gm is not fully understood. Arabidopsis thaliana wild-type and carbon-metabolism mutants (gwd1, pgm1, and cfbp1) with different accumulation patterns of non-structural carbohydrates were grown at ambient (400 ppm) and elevated (800 ppm) CO2. Anatomical and physiological traits of leaves were measured to investigate factors causing the changes in gm and in the mesophyll resistance (expressed as the reciprocal of mesophyll conductance per unit chloroplast surface area facing to intercellular space, Sc/gm). When grown at elevated CO2, all the lines showed increases in cell wall mass, cell wall thickness, and starch content, but not in leaf thickness. gm measured at 800 ppm CO2 was significantly lower than at 400 ppm CO2 in all the lines. Changes in Sc/gm were associated with thicker cell walls rather than with excess starch content. The results indicate that the changes in gm and Sc/gm that occur in response to elevated CO2 are independent of non-structural carbohydrates, and the cell wall represents a greater limitation factor for gm than starch.


Assuntos
Arabidopsis/fisiologia , Dióxido de Carbono/metabolismo , Células do Mesofilo/efeitos dos fármacos , Cloroplastos/efeitos dos fármacos , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Células do Mesofilo/metabolismo , Células do Mesofilo/ultraestrutura , Microscopia Eletrônica de Transmissão , Folhas de Planta/metabolismo
7.
Int J Mol Sci ; 20(12)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234590

RESUMO

When leaves receive excess light energy, excess reductants accumulate in chloroplasts. It is suggested that some of the reductants are oxidized by the mitochondrial respiratory chain. Alternative oxidase (AOX), a non-energy conserving terminal oxidase, was upregulated in the photosynthetic mutant of Arabidopsis thaliana, pgr5, which accumulated reductants in chloroplast stroma. AOX is suggested to have an important role in dissipating reductants under high light (HL) conditions, but its physiological importance and underlying mechanisms are not yet known. Here, we compared wild-type (WT), pgr5, and a double mutant of AOX1a-knockout plant (aox1a) and pgr5 (aox1a/pgr5) grown under high- and low-light conditions, and conducted physiological analyses. The net assimilation rate (NAR) was lower in aox1a/pgr5 than that in the other genotypes at the early growth stage, while the leaf area ratio was higher in aox1a/pgr5. We assessed detailed mechanisms in relation to NAR. In aox1a/pgr5, photosystem II parameters decreased under HL, whereas respiratory O2 uptake rates increased. Some intermediates in the tricarboxylic acid (TCA) cycle and Calvin cycle decreased in aox1a/pgr5, whereas γ-aminobutyric acid (GABA) and N-rich amino acids increased in aox1a/pgr5. Under HL, AOX may have an important role in dissipating excess reductants to prevent the reduction of photosynthetic electron transport and imbalance in primary metabolite levels.


Assuntos
Arabidopsis/fisiologia , Arabidopsis/efeitos da radiação , Transporte de Elétrons , Luz , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Proteínas Mitocondriais/metabolismo , Oxirredução , Oxirredutases/metabolismo , Fotossíntese/efeitos da radiação , Proteínas de Plantas/metabolismo , Biomarcadores , Metabolismo Energético , Regulação da Expressão Gênica
8.
Plant Cell Physiol ; 58(12): 2043-2056, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29216401

RESUMO

To clarify whether excessive accumulation of total non-structural carbohydrate (TNC) causes down-regulation of photosynthesis in Raphanus sativus, we manipulated sink-source balance to alter TNC levels in source leaves and examined its effects on photosynthetic characteristics, whole-plant biomass allocation and anatomical characteristics of leaves and petioles. Comet and Leafy varieties with large and small hypocotyls were reciprocally grafted to change hypocotyl sink strength. They were grown at high or low nitrogen (N) availability and at elevated or ambient CO2. Maximum photosynthetic rate, which was highly correlated with Rubisco and leaf N contents, was hardly correlated with TNC across the grafting combinations and growth conditions. Biomass allocation to petioles and hypocotyls and accumulation of TNC in each organ were significantly higher at low N. TNC and structural carbohydrates such as cellulose and hemicellulose were higher and the proportion of intercellular air space in source leaves was lower at low N and elevated CO2. We conclude that excess TNC does not cause severe down-regulation of photosynthesis, and cell walls and petioles are also major carbohydrate sinks responding to changes in sink-source and carbon-nitrogen balances, which contribute to alleviating further accumulation of TNC to avoid its negative effects in source leaves.


Assuntos
Dióxido de Carbono/metabolismo , Nitrogênio/metabolismo , Fotossíntese/fisiologia , Raphanus/fisiologia , Metabolismo dos Carboidratos , Carbono/metabolismo , Parede Celular/metabolismo , Celulose/metabolismo , Regulação para Baixo , Folhas de Planta/anatomia & histologia , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo , Raphanus/crescimento & desenvolvimento , Ribulose-Bifosfato Carboxilase/metabolismo
9.
Plant Cell Physiol ; 57(7): 1426-1431, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26903530

RESUMO

Respiratory electron transport has two ubiquinol-oxidizing pathways, the cytochrome pathway (CP) and the alternative pathway (AP). The AP, which is catalyzed by the alternative oxidase (AOX), is energetically wasteful but may alleviate PSII photoinhibition under light conditions excessive for photosynthesis. However, its mechanism remains unknown. We used Arabidopsis aox1a mutants lacking AOX activity and studied the mutation's effects on photoinhibition by measuring the decrease in the maximum quantum yield of PSII (Fv/Fm) after high light exposure. Since the CP compensates for the lack of AOX, we monitored the extent of photoinhibition under conditions where CP activity is partially inhibited by antimycin A. When leaves were exposed to high light at 350 µmol m-2 s-1, the decline in Fv/Fm was significantly faster in the aox1a mutants than in the wild type. However, under conditions where photorespiration was suppressed by high CO2 or low O2 levels, the decline in Fv/Fm was suppressed in the aox1a mutants, but not in the wild type, making the difference between the wild type and mutants small. Our results demonstrate that the lack of the AP causes an acceleration of PSII photoinhibition in relation to the photorespiratory pathway, suggesting that the AP can support the activity of the photorespiratory pathway under high light conditions.


Assuntos
Arabidopsis/fisiologia , Arabidopsis/efeitos da radiação , Luz , Mitocôndrias/metabolismo , Processos Fotoquímicos/efeitos da radiação , Complexo de Proteína do Fotossistema II/metabolismo , Transdução de Sinais/efeitos da radiação , Antimicina A/farmacologia , Arabidopsis/efeitos dos fármacos , Dióxido de Carbono/farmacologia , Respiração Celular/efeitos dos fármacos , Respiração Celular/efeitos da radiação , Cloranfenicol/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Proteínas Mitocondriais/metabolismo , Mutação/genética , Oxirredutases/metabolismo , Oxigênio/farmacologia , Processos Fotoquímicos/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Histochem Cell Biol ; 146(1): 59-69, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26976000

RESUMO

In eukaryotic cells, Rab guanosine triphosphate-ases serve as key regulators of membrane-trafficking events, such as exocytosis and endocytosis. Rab3, Rab6, and Rab27 control the regulatory secretory pathway of neuropeptides and neurotransmitters. The cDNAs of Rab3, Rab6, and Rab27 from B. mori were inserted into a plasmid, transformed into Escherichia coli, and then subsequently purified. We then produced antibodies against Rab3, Rab6, and Rab27 of Bombyx mori in rabbits and rats for use in western immunoblotting and immunohistochemistry. Western immunoblotting of brain tissue revealed a single band at approximately 26 kDa. Immunohistochemistry results revealed that Rab3, Rab6, and Rab27 expression was restricted to neurons in the pars intercerebralis and dorsolateral protocerebrum of the brain. Rab3 and Rab6 co-localized with bombyxin, an insect neuropeptide. However, there was no Rab that co-localized with prothoracicotropic hormone. The corpus allatum secretes neuropeptides synthesized in the brain into the hemolymph. Results showed that Rab3 and Rab6 co-localized with bombyxin in the corpus allatum. These findings suggest that Rab3 and Rab6 are involved in neurosecretion in B. mori. This study is the first to report a possible relationship between Rab and neurosecretion in the insect corpus allatum.


Assuntos
Bombyx/química , Encéfalo/imunologia , Corpora Allata/química , Corpora Allata/imunologia , Proteínas rab de Ligação ao GTP/análise , Animais , Anticorpos/imunologia , Bombyx/imunologia , Imuno-Histoquímica , Coelhos , Ratos , Proteínas rab de Ligação ao GTP/imunologia
11.
Plant Cell Physiol ; 56(11): 2069-78, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26423961

RESUMO

Elevated atmospheric CO(2) concentrations ([CO(2)]) affect primary metabolite levels because CO(2) is a direct substrate for photosynthesis. In several studies, the responses of primary metabolite levels have been examined using Arabidopsis thaliana leaves, but these results have not been comprehensively discussed. Here, we examined metabolome data for A. thaliana accession Col-0 leaves that were grown at elevated [CO(2)] with sufficient nitrogen (N) nutrition. At elevated [CO(2)], starch, monosaccharides and several major amino acids accumulated in leaves. The degree of accumulation depended on whether the rooting medium contained NH(4) (+) or only NO(3) (-). Because low N conditions induce an increase in carbohydrates similar to that of elevated [CO(2)], we compared the responses of primary metabolite levels between elevated [CO(2)] and low N conditions. Levels of the tricarboxylic acid (TCA) cycle-associated organic acids and major amino acids decreased with low N, but not with elevated [CO(2)]. Even at elevated [CO(2)], the low N induced the decreases in the levels of organic acids and major amino acids. A small sink size also affects the primary metabolite response patterns in leaves under elevated [CO(2)] conditions. Thus, care is necessary when interpreting primary metabolite changes in leaves of field-grown plants.


Assuntos
Arabidopsis/metabolismo , Dióxido de Carbono/metabolismo , Folhas de Planta/metabolismo , Metabolismo dos Carboidratos , Respiração Celular , Ciclo do Ácido Cítrico , Glicólise , Metabolômica , Nitrogênio/metabolismo , Fotossíntese
12.
Curr Genet ; 61(1): 43-53, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25119673

RESUMO

It is unclear whether local anesthetics, such as tetracaine, and antipsychotics, such as phenothiazines, act on lipids or proteins. In Saccharomyces cerevisiae, these drugs inhibit growth, translation initiation, and actin polarization, and induce cell lysis at high concentrations. These activities are likely due to the cationic amphiphilic structure common to these agents. Although drug-induced translational inhibition is conserved in mammalian cells, other mechanisms, including the phosphorylation of eIF2α, a eukaryotic translational initiation factor, remain poorly understood. At a concentration of 10 mM, tetracaine rapidly inhibited translation initiation and lysed cells, whereas, at 2.5 mM, it slowly induced inhibition without lysis. The pat1 disruptant defective in mRNA decapping and the xrn1 disruptant defective in 5'-3' exoribonuclease were partially resistant to translational inhibition by tetracaine at each concentration, but the gcn2 disruptant defective in the eIF2α kinase was not. Phosphorylation of eIF2α was induced by 10 mM but not by 2.5 mM tetracaine, whereas processing bodies (P-bodies) were formed at 2.5 mM in Pat1-dependent and -independent manners. Therefore, administration of tetracaine inhibits translation initiation with P-body formation at both concentrations but acts via the Gcn2-eIF2α system only at the higher concentration. Because other local anesthetics and phenothiazines induced Pat1-dependent P-body formation, the mechanisms involved in translational inhibition by these cationic amphiphiles are similar. These results suggest that this dose-dependent biphasic translational inhibition by tetracaine results from an increase in membrane proteins that are indirectly inhibited by nonspecific interactions of cationic amphiphiles with membrane lipids.


Assuntos
Anestésicos Locais/farmacologia , Fator de Iniciação 2 em Eucariotos/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Tetracaína/farmacologia , Leveduras/efeitos dos fármacos , Leveduras/fisiologia , Mutação , Fosforilação/efeitos dos fármacos , Transporte Proteico , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/fisiologia , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Plant Cell Physiol ; 55(2): 341-57, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24319073

RESUMO

Elevated CO2 affects plant growth and photosynthesis, which results in changes in plant respiration. However, the mechanisms underlying the responses of plant respiration to elevated CO2 are poorly understood. In this study, we measured diurnal changes in the transcript levels of genes encoding respiratory enzymes, the maximal activities of the enzymes and primary metabolite levels in shoots of Arabidopsis thaliana grown under moderate or elevated CO2 conditions (390 or 780 parts per million by volume CO2, respectively). We examined the relationships between these changes and respiratory rates. Under elevated CO2, the transcript levels of several genes encoding respiratory enzymes increased at the end of the light period, but these increases did not result in changes in the maximal activities of the corresponding enzymes. The levels of some primary metabolites such as starch and sugar phosphates increased under elevated CO2, particularly at the end of the light period. The O2 uptake rate at the end of the dark period was higher under elevated CO2 than under moderate CO2, but higher under moderate CO2 than under elevated CO2 at the end of the light period. These results indicate that the changes in O2 uptake rates are not directly related to changes in maximal enzyme activities and primary metabolite levels. Instead, elevated CO2 may affect anabolic processes that consume respiratory ATP, thereby affecting O2 uptake rates.


Assuntos
Arabidopsis/fisiologia , Dióxido de Carbono/farmacologia , Respiração Celular , Regulação da Expressão Gênica de Plantas , Fotossíntese , Folhas de Planta/fisiologia , Trifosfato de Adenosina/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Metabolismo dos Carboidratos , Dióxido de Carbono/metabolismo , Ritmo Circadiano , Luz , Oxigênio/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/efeitos da radiação , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/genética , Brotos de Planta/fisiologia , Brotos de Planta/efeitos da radiação
14.
Food Res Int ; 182: 114173, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519188

RESUMO

Wet-type grinder (WG) is a nanofiber technology used to atomize dietary fiber-rich materials. WG-treated okara (WGO) exhibits high dispersion and viscosity similar to those of viscous soluble dietary fibers. Here, we studied the effect of WGO supplementation on obesity and gut microbiota composition in high-fat diet (HFD)-fed mice. WGO intake suppressed body weight gain and fat accumulation, improved glucose tolerance, lowered cholesterol levels, and prevented HFD-induced decrease in muscle mass. WGO supplementation also led to cecum enlargement, lower pH, and higher butyrate production. The bacterial 16S ribosomal RNA genes (16S rDNA) were sequenced to determine the gut microbiota composition of the fecal samples. Sequencing of bacterial 16S rDNA revealed that WGO treatment increased the abundance of butyrate producer Ruminococcus and reduced the abundances of Rikenellaceae, Streptococcaceae, and Prevotellaceae, which are related to metabolic diseases. Metabolomics analysis of the plasma of WGO- and cellulose-treated mice were conducted using ultra-high-performance liquid chromatography-mass spectrometry. Metabolic pathway analysis revealed that the primary bile acid biosynthesis pathway was significantly positively regulated by WGO intake instead of cellulose. These results demonstrate that WG is useful for improving functional properties of okara to prevent metabolic syndromes, including obesity, diabetes, and dyslipidemia.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Obesidade/tratamento farmacológico , Obesidade/prevenção & controle , Obesidade/metabolismo , Celulose/farmacologia , Butiratos , DNA Ribossômico/farmacologia
15.
Am J Surg Pathol ; 48(6): 671-680, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497417

RESUMO

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples ( P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.


Assuntos
Biomarcadores Tumorais , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B , Proteínas de Ligação a RNA , Humanos , Biomarcadores Tumorais/análise , Proteínas de Ligação a RNA/análise , Masculino , Feminino , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Neoplasias Vasculares/patologia , Neoplasias Vasculares/química , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
16.
Biochem Biophys Res Commun ; 435(4): 657-63, 2013 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-23688426

RESUMO

Autophagy is a self-proteolysis process in eukaryotic cells that results in the sequestering of intracellular proteins and organelles in autophagosomes. Activation of autophagy progress continued growth of some tumors, instead extensive autophagy induces cell death. In a previous study, we synthesized a novel tamoxifen derivative, Ridaifen (RID)-B. RID-B induced mitochondria-involved apoptosis even in estrogen receptor (ER)-negative cells. Since tamoxifen induces autophagy other than apoptosis, we treated ER-negative Jurkat cells with RID-B in the present study. RID-B treatment induced apoptosis and LC3 and lysosome colocalization, which results in the formation of autolysosomes. Western blotting revealed that LC3 was converted to LC3-I to LC3-II with RID-B treatment, suggesting that RID-B induced autophagy without ER involvement. Moreover, overexpression of the anti-apoptotic protein Bcl-2 suppressed the RID-B-induced cell death, but not the induction of autophagy. These results presumed that RID-B-induced autophagy is independent of Bcl-2, making RID-B-induced autophagy different from RID-B-induced apoptosis. Since Beclin 1 level is unchanged during RID-B treatment, RID-B induced autophagy pathway is Bcl-2/Beclin1 independent noncanonical pathway.


Assuntos
Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirrolidinas/administração & dosagem , Receptores de Estrogênio/metabolismo , Tamoxifeno/análogos & derivados , Antineoplásicos Hormonais/administração & dosagem , Humanos , Células Jurkat , Tamoxifeno/administração & dosagem
17.
Bioorg Med Chem ; 21(1): 311-20, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23199482

RESUMO

Ridaifen B (RID-B) is a tamoxifen derivative that potently inhibits breast tumor growth. RID-B was reported to show anti-proliferating activity for a variety of estrogen receptor (ER)-positive human cancer cells. Interestingly, RID-B was also reported to possess higher potency than that of tamoxifen even for some ER-negative cells, suggesting an ER-independent mechanism of action. In this study, a T7 phage display screen and subsequent binding analyses have identified Grb10 interacting GYF protein 2 (GIGYF2) as a RID-B-binding protein. Using a cell-based assay, the Akt phosphorylation level mediated by GIGYF2 was found to have decreased in the presence of RID-B.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Transporte/metabolismo , Pirrolidinas/farmacologia , Tamoxifeno/análogos & derivados , Sequência de Aminoácidos , Proteínas de Transporte/química , Linhagem Celular Tumoral , Técnicas de Visualização da Superfície Celular , Humanos , Dados de Sequência Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia
18.
World J Surg Oncol ; 11(1): 184, 2013 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-23938043

RESUMO

Although uncommon, ovarian cancer cells may spread to the rectal lymph nodes. However, few reports have described how to detect and treat such metastases. We report a case of a 59-year-old woman with mesorectal and pararectal lymph node metastases in recurrent ovarian carcinoma, detected conclusively using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and treated by low anterior resection with total mesorectal excision aiming for macroscopic complete resection. The treatment goals for the patient were gradually changed from curative to palliative chemotherapy; she survived for 45 months without rectal obstruction after secondary debulking surgery, and was followed up until autopsy. Thus, 18F-FDG PET/CT may be valuable for detecting rectal lymph node metastasis and can play an essential role in planning treatment for recurrent ovarian carcinoma.


Assuntos
Fluordesoxiglucose F18 , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Tomografia por Emissão de Pósitrons , Neoplasias Retais/secundário , Tomografia Computadorizada por Raios X , Terapia Combinada , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Prognóstico , Compostos Radiofarmacêuticos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia
19.
Sci Rep ; 13(1): 7537, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217488

RESUMO

We explored risk indicators likely to result in older adults needing certified long-term care in Japan and ascertained whether this relationship forms a U-shaped link. We analyzed a community-based cohort of residents in Kitanagoya City, Aichi Prefecture, Japan. Participants were 3718 individuals aged 65 years and above who underwent health examinations between April 1, 2011 and March 31, 2012. For continuous clinical variables, we applied a time-dependent Cox regression model. Two types of models were applied-a linear and nonlinear model with restricted cubic splines-to assess the U-shaped association. Statistical significance (set at 0.05) for the nonlinearity was tested by comparing the spline and linear models. Among the participants, 701 were certified as needing Level 1 care or higher during a follow-up. Among the continuous clinical variables, the nonlinear model for body mass index, systolic blood pressure, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase revealed significant U-shaped associations as compared with the linear model in which the outcome was a certification of the need for nursing care. These results provide an important insight into the usefulness of nonlinear models for predicting the risk of such certification.


Assuntos
Assistência de Longa Duração , Humanos , Idoso , Modelos de Riscos Proporcionais , Fatores de Risco , HDL-Colesterol , Japão
20.
J Oleo Sci ; 72(12): 1125-1131, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38044136

RESUMO

Consumption of a high-fat diet (HFD) is associated with an increased risk of metabolic diseases, cancer, and neurological disorders, which are major global health concerns. In the present study, mice were fed a HFD containing 40% fat and 0.5% or 1.0% acylated steryl-ß-glucosides (ASG) and their gut microbiota was compared to that of mice fed with a low-fat diet (LFD). After 55 d, the epididymal fat weight was higher in the HFD and ASG groups than in the LFD group; however, the epididymal fat weight was lower in the ASG group than in the HFD group. The abundance of gut microbiota increased with HFD in obese micespecific Bacillota, but decreased when ASG was added to the HFD. The number of intestinal bacteria involved in the production of carcinogenic secondary bile acids was increased by the consumption of HFD, but decreased by the addition of ASG to HSD. This finding may indicate the gut bacteria-mediated health benefits of ASG.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Glicosídeos , Sacarose , Obesidade/microbiologia , Glucosídeos
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