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1.
Acta Crystallogr A Found Adv ; 77(Pt 2): 138-148, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646200

RESUMO

The coordination sequence of a graph measures how many vertices the graph has at each distance from a fixed vertex and is a generalization of the coordination number. Here it is proved that the coordination sequence of the graph obtained from a crystal is of quasi-polynomial type, as had been postulated by Grosse-Kunstleve et al. [Acta Cryst. (1996), A52, 879-889].

2.
Cancer Commun (Lond) ; 41(1): 83-87, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33387444

RESUMO

Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene (MET) exon 14 skipping mutation. However, its bioavailability in the cerebrospinal fluid (CSF) in humans has not been fully elucidated. Moreover, information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited. Here, we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation. He was urgently hospitalized due to leptomeningeal metastasis. We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status. The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF, with a penetration rate (CSF/plasma) of 1.83%. These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.

3.
Sci Rep ; 11(1): 785, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436910

RESUMO

(R-)miniCHOP therapy, which delivers approximately half-doses of the (R-)CHOP regimen, has shown efficacy and safety in patients who are more than 80 years old. This study aimed to compare the area under the plasma concentration-time curves (AUCs) of vincristine (VCR), doxorubicin (DXR), and cyclophosphamide (CPA) between (R-)CHOP and (R-)miniCHOP regimens. The AUCs were compared between patients aged 65-79 years receiving (R-)CHOP therapy and those aged 80 years and older receiving (R-)miniCHOP therapy. Age was not an independent variable for predicting the dose-adjusted AUCs (AUC/Ds) of cytotoxic anticancer drugs. The median AUCs of DXR and CPA were significantly smaller in the (R-)miniCHOP group than in the (R-)CHOP group (168.7 vs. 257.9 ng h/mL, P = 0.003, and 219.9 vs. 301.7 µg h/mL, P = 0.020, respectively). The median AUCs of VCR showed the same trend but the difference was not significant (24.83 vs. 34.85 ng h/mL, P = 0.135). It is possible that the AUCs of VCR, DXR, and CPA in patients aged 80 years and older receiving (R-)miniCHOP therapy may be lower than those in patients 65-79 years old receiving (R-)CHOP therapy.

4.
Nutrients ; 12(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927677

RESUMO

Vascular dysfunction and injurious stimuli such as oxidative stress are closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols are reported to exert beneficial effects in reducing the risk of CVD. Black soybean has been used as a nutritionally rich food and contains abundant polyphenols in its seed coat and grain. Black soybean has many beneficial physiological activities, and its prevention effects on CVD risk were reported mainly in animal experiments. In this study, we performed a randomized, single blind, placebo controlled, crossover trial to investigate the effect of black soybean consumption on the vascular function in healthy humans. Twenty-two healthy adults aged from 30 to 60 completed the four week trial with daily consumption of about a 40 g test material cookie containing 20 g roasted black soybean powder. Body composition, vascular function, biomarkers for oxidative stress, and polyphenol contents in the urine and the plasma were measured. After ingestion of the black soybean cookie, vascular function, which was evaluated by plethysmogram using a Pulse Analyzer®, was improved and systolic blood pressure was decreased. Moreover, nitric oxide levels in plasma and urine were increased, while an oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine level, in the plasma was decreased accompanied by an increase in the concentration of polyphenols derived from black soybean in plasma and urine. These results suggest that the antioxidant activity of black soybean polyphenols and an increase in the nitric oxide level may contribute to the improvement of vascular function. Thus, black soybean is an attractive food material for improvement of vascular function through decreasing oxidative stress by its potent antioxidant activity and increasing the nitric oxide level in healthy humans.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32920985

RESUMO

Rivaroxaban is excreted from the body via multiple pathways involving glomerular filtration, drug-metabolizing enzymes and transporters. In this study, we aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, breast cancer resistance protein, cytochrome P450 (CYP) 3A5 and CYP2J2 on the pharmacokinetics of rivaroxaban. Eighty-six patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation were enrolled in this study. In these analyses, the dose-adjusted plasma trough concentration ratio (C0h /D) of rivaroxaban was used as the pharmacokinetic index. The median (quartile range) rivaroxaban C0h /D was 3.39 (2.08-5.21) ng/mL/mg (coefficient of variation: 80.5%). The C0h /D did not differ significantly among ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T, ABCG2 c.421C>A, CYP3A5*3 and CYP2J2*7 genotypes. Stepwise selection multiple linear regression analysis showed that the estimated glomerular filtration rate was the only independent factor influencing the C0h /D of rivaroxaban (R2  = 0.152, P < 0.001). There was a significant correlation between the C0h of rivaroxaban and prothrombin time (PT) (rho = 0.357, P = 0.001). In patients with NVAF, pharmacokinetic genotype tests are unlikely to be useful for prediction of the C0h of rivaroxaban.

6.
Eur J Drug Metab Pharmacokinet ; 45(5): 619-626, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32514937

RESUMO

BACKGROUND AND OBJECTIVE: Tacrolimus clearance (CL) is significantly altered according to recovery of liver function at an early stage after living donor liver transplantation (LDLT). In this study, we aimed to examine the impact of the change rate from postoperative day (POD) 1 in CL (ΔCL) of tacrolimus during continuous intravenous infusion (CIVI) on recipient recovery. METHODS: A tacrolimus population pharmacokinetic model on POD1 after LDLT was developed using Phoenix NLME 1.3. The CLPOD1 was calculated using the final model. The CLPOD4-7 was calculated by dividing total daily tacrolimus dose by the area under the concentration-time curve from 0 to 24 h. RESULTS: Data were obtained from 57 LDLT recipients, along with 540 points (177 points on POD1, 363 points on POD4-7) of tacrolimus whole blood concentrations at CIVI. The median tacrolimus CL decreased from POD1 to POD4 (from 2.73 to 1.40 L/h) and was then stable until POD7. Stepwise Cox proportional hazards regression analyses showed that the graft volume (GV)/standard liver volume (SLV) ratio (GV/SLV) and the tacrolimus ΔCLPOD6 were independent factors predicting early discharge (within 64 days median value) of recipients after LDLT [hazard ratio (HR) = 1.041, P = 0.001 and HR = 1.023, P = 0.004]. CONCLUSIONS: The tacrolimus ΔCL during CIVI immediately after LDLT in each recipient was a useful indicator for evaluation of recovery at an early stage after LDLT.

7.
Arch Biochem Biophys ; 688: 108408, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32470460

RESUMO

Vascular dysfunction and injurious stimuli such as oxidative stress is closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols is reported to exert the beneficial effects on reducing the risk of CVD. Black soybean is rich in polyphenols, including isoflavones, anthocyanidins and flavan-3-ols, and its prevention effects on CVD risk were reported in the animal experiments. In this study, we investigated the effect of black soybean consumption on the vascular function and oxidative stress associating with the polyphenol concentrations in healthy women. Lowered vascular age was observed in 33 out of 44 volunteers who completed the 8-week trial. It was observed that improvement of the vascular stiffness, increasing in the urinary NO2 and NO3 level, and decreasing in the oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, hexanoyl-lysine and myeloperoxidase. In addition, concentration of 12 polyphenols in black soybean increased in the plasma and urine. Increased concentration of polyphenols would be involved in the decreased oxidative stress. Thus, black soybean consumption improved the vascular function through an increase in nitric oxide and a decrease in oxidative stress accompanied by increasing the polyphenol concentrations in healthy women.


Assuntos
Antioxidantes/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Soja/química , Administração Oral , Adulto , Idoso , Animais , Antioxidantes/administração & dosagem , Antioxidantes/análise , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Pressão Sanguínea , Feminino , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico/urina , Fotopletismografia , Polifenóis/administração & dosagem , Polifenóis/sangue , Polifenóis/urina , Adulto Jovem
8.
Mod Rheumatol ; : 1-9, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32149542

RESUMO

Objectives: Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-positive and age at onset ≥60 years are poor prognosis factors in polymyositis (PM) and dermatomyositis (DM) associated with interstitial lung disease (ILD) among Japanese patients. However, the influence of age on the clinical features of anti-MDA5 autoantibody-positive patients with DM remains unclear.Methods: We retrospectively examined 40 patients with DM and anti-MDA5 autoantibodies according to age. We compared patients aged <60 and ≥60 years with respect to clinical features including laboratory test findings, high-resolution lung computed tomography data, treatment content, and complications such as infections and prognosis. We also examined clinical features between surviving and deceased patients in the older patient group.Results: Of 40 enrolled patients, 13 were classified as old and 27 as young. Older patients had significantly fewer clinical symptoms including arthralgia/arthritis (p < .01), skin ulceration (p = .02), and higher mortality than younger patients (p = .02) complicated with rapidly progressive ILD (RP-ILD), combination immunosuppressive therapy, and strictly controlled infections.Conclusion: Clinical features and mortality of anti-MDA5 autoantibody-positive DM patients were influenced by age. Patients aged ≥60 years had a worse prognosis, and combination immunosuppressive therapy was often ineffective for RP-ILD in older patients.

9.
Microbes Environ ; 34(4): 402-412, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31631078

RESUMO

Thiocyanate (SCN-) is harmful to a wide range of organisms, and its removal is essential for environmental protection. A neutrophilic halophile capable of thiocyanate degradation, Thiohalobacter sp. strain FOKN1, was highly enriched (relative abundance; 98.4%) from activated sludge collected from a bioreactor receiving thiocyanate-rich wastewater. The enrichment culture degraded 3.38 mM thiocyanate within 140 h, with maximum activity at pH 8.8, 37°C, and 0.18 M sodium chloride. Thiocyanate degradation was inhibited by 30 mg L-1 phenol, but not by thiosulfate. Microbial thiocyanate degradation is catalyzed by thiocyanate dehydrogenase, while limited information is currently available on the molecular mechanisms underlying thiocyanate degradation by the thiocyanate dehydrogenase of neutrophilic halophiles. Therefore, (meta)genomic and proteomic analyses of enrichment cultures were performed to elucidate the whole genome sequence and proteome of Thiohalobacter sp. strain FOKN1. The 3.23-Mb circular Thiohalobacter sp. strain FOKN1 genome was elucidated using a PacBio RSII sequencer, and the expression of 914 proteins was identified by tandem mass spectrometry. The Thiohalobacter sp. strain FOKN1 genome had a gene encoding thiocyanate dehydrogenase, which was abundant in the proteome, suggesting that thiocyanate is degraded by thiocyanate dehydrogenase to sulfur and cyanate. The sulfur formed may be oxidized to sulfate by the sequential oxidation reactions of dissimilatory sulfite reductase, adenosine-5'-phosphosulfate reductase, and dissimilatory ATP sulfurylase. Although the Thiohalobacter sp. strain FOKN1 genome carried a gene encoding cyanate lyase, its protein expression was not detectable. The present study advances the understanding of the molecular mechanisms underlying thiocyanate degradation by the thiocyanate dehydrogenase of neutrophilic halophiles.


Assuntos
Gammaproteobacteria/metabolismo , Genoma Bacteriano/genética , Esgotos/microbiologia , Tiocianatos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Reatores Biológicos/microbiologia , DNA Bacteriano/genética , Gammaproteobacteria/classificação , Gammaproteobacteria/genética , Redes e Vias Metabólicas , Filogenia , Proteoma/metabolismo , RNA Ribossômico 16S/genética , Esgotos/química , Tiocianatos/análise
10.
Anaerobe ; 51: 110-119, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29734011

RESUMO

Prebiotic oligosaccharides are known to have significant impacts on gut microbiota and are thus widely used to program healthy microbiota composition and activity from infants to the elderly. Bifidobacteria and lactobacilli are among the major target microorganisms of oligosaccharides, but the metabolic properties of oligosaccharides in other predominant gut microbes have not been well characterized. In the present study, we demonstrated the metabolic properties of six oligosaccharides in 31 key gut anaerobes. Bifidobacteria readily metabolized fructooligosaccharide (FOSs) with degree of polymerization (DP) 3, i.e. 1-kestose, but several strains used did not actively metabolize FOSs with DP4 and DP5, i.e. nystose and fructosylnystose. Akkermansia muciniphila, a potential new probiotic against obesity, did not show significant growth with any of the oligosaccharides tested. The butyrate producer Anaerostipes caccae grew well on 1-kestose but poorly on FOS mixtures, whereas it contained 1-kestose at 30%. Bacteroides-Parabacteroides group species were separated into two groups based on oligosaccharide metabolic properties. One group metabolized well most of the oligosaccharides tested, but the others metabolized only 1 or 2 selected oligosaccharides. Oligosaccharide profiles after culturing revealed that Bifidobacterium spp. preferentially metabolized shorter oligosaccharides (DP3) in the mixtures, whereas Bacteroides-Parabacteroides spp. did not show oligosaccharide selectivity for metabolism or rather preferred longer oligosaccharides (>DP4). The fermentation profiles indicated specific links between the microbial end-products and specific gut microbes. Available carbohydrates had a significant impact on the accumulation of amino acid-derived bacterial metabolites (i.e. phenol, p-cresol, indole and skatole) and short chain fatty acids. The results assist in predicting the impact of oligosaccharides in human intervention and gut microbiota modulation.


Assuntos
Bactérias Anaeróbias/crescimento & desenvolvimento , Bactérias Anaeróbias/metabolismo , Oligossacarídeos/metabolismo , Prebióticos , Bactérias Anaeróbias/isolamento & purificação , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Microbiota/efeitos dos fármacos
11.
Biosci Biotechnol Biochem ; : 1-10, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499629

RESUMO

Sirtuin has been associated in prolonging lifespan of different model organisms. It has been shown to have an enzymatic activity of NAD+-dependent protein deacetylation targeting acetylated proteins. To determine targets and possible roles of sirtuin (LpSirA) in the Lactobacillus paracasei BL23, deletion (ΔsirA), sirtuin overexpressor (highsirA) and GFP fusion (highsirA-Venus) strains were generated, and microscopic localization and cell length analysis were done. Microscopic analysis revealed localization of LpSirA at cell division plates, at cell poles and all throughout the cell length in a spiral manner. Cell length analysis revealed that 46.9% of the ΔsirA cells were observed to be shorter (<2 µm), whereas 12.6% of the highsirA cells were observed to be longer (>4 µm) in comparison with the wild-type with only 17.1% short cells and 5.3% long cells. Our results suggest that sirtuin may have an essential role in cell division and cell shape regulation.

12.
Int J Food Sci Nutr ; 69(7): 857-869, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29318897

RESUMO

Soymilk contains several functional nutrients and is thus a promising ingredient for production of functional foods. The present research aimed to study starter properties, functional characteristics and safety of Lactobacillus paraplantarum D2-1, a promising starter culture for soymilk fermentation. Strain D2-1 actively fermented soymilk within 24 h but had weak activity of additional acid production after 7 d. Succinate and acetoin, which could be linked to flavour and taste, were accumulated in fermented soymilk. In vitro study revealed that the organism has several beneficial properties, including high survival ability in artificial gastric juice, high abilities of mucus adhesion and biofilm formation and production of γ-aminobutyric acid and conjugated linoleic acid, without any significant risks for consumption. Genome sequencing supported the desirable metabolic properties of the strain. These results indicate that L. paraplantarum D2-1 is a suitable starter for soymilk fermentation and is a promising probiotic candidate that can be used safely.


Assuntos
Alimentos e Bebidas Fermentados , Microbiologia de Alimentos , Lactobacillus , Probióticos , Leite de Soja/química , Acetoína/análise , Fermentação , Inocuidade dos Alimentos , Metaboloma , Ácido Succínico/análise
13.
Biosci Microbiota Food Health ; 36(4): 147-149, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29038770

RESUMO

Potential fructophilic characteristics of Lactobacillus apinorum, originally isolated from the guts of honeybees (Apis mellifera), were studied in the present study. The species showed typical fructophilic growth characteristics, i.e., active growth on d-fructose, poor growth on d-glucose, and accelerated growth on d-glucose in the presence of electron acceptors. Biochemical characteristics strongly supported classification of the species into fructophilic lactic acid bacteria (FLAB). Furthermore, genetic analyses suggested that the species underwent extensive gene reduction, similar to that recorded for Lactobacillus kunkeei and other FLAB. These data clearly indicated that L. apinorum is the second fructophilic species within the genus Lactobacillus.

14.
Genome Announc ; 5(32)2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798190

RESUMO

A draft genome sequence of a neutrophilic halophile capable of thiocyanate degradation, Thiohalobacter thiocyanaticus FOKN1, was determined using a PacBio RSII sequencer. A 3.23-Mb circular genome sequence was assembled, in which 3,026 gene-coding sequences, 45 tRNAs, and 1 rrn operon were annotated.

15.
Biosci Microbiota Food Health ; 36(2): 65-72, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439489

RESUMO

Penicillin-binding proteins (PBPs) are responsible for peptidoglycan synthesis. By using biotinylated ampicillin, we detected PBPs of Lactobacillus paracasei strains. Ten PBPs were identified, 7 of which had apparent molecular sizes similar to those of Escherichia coli. In the presence of cholate, strain NRIC 0625 showed an elongated shape, and its putative PBP3 showed cholate-sensitive penicillin-binding activity. Furthermore, this strain was highly sensitive to cefalexin, which is known to inhibit cell division by inactivating PBP3. These results suggest that the septum synthetase PBP3 of lactic acid bacteria can be one of the targets of intestinal bile acid.

16.
Clin Nucl Med ; 42(3): e157-e160, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28005638

RESUMO

Cartilaginous tumors of the larynx are uncommon neoplasms that sometimes mimic laryngeal cancers. There has been no report of F-FDG PET/CT for the evaluation of laryngeal cartilaginous tumors. We reported 3 cases of laryngeal cartilaginous tumors with the image findings, including CT, FDG PET/CT, and MRI and reviewed literatures. We concluded that the combination of a very high-signal mass on T2-weighted magnetic resonance images and lower FDG uptake might be diagnostic image characteristics for distinguishing laryngeal cartilaginous tumor from laryngeal cancer.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Cartilagem/diagnóstico por imagem , Neoplasias Laríngeas/diagnóstico por imagem , Imagem por Ressonância Magnética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fluordesoxiglucose F18 , Humanos , Compostos Radiofarmacêuticos
17.
Syst Appl Microbiol ; 39(8): 516-526, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27776911

RESUMO

Lactobacillus kunkeei is classified as a sole obligate fructophilic lactic acid bacterium that is found in fructose-rich niches, including the guts of honeybees. The species is differentiated from other lactobacilli based on its poor growth with glucose, enhanced growth in the presence of oxygen and other electron acceptors, and production of high concentrations of acetate from the metabolism of glucose. These characteristics are similar to phylogenetically distant Fructobacillus spp. In the present study, the genomic structure of L. kunkeei was characterized by using 16 different strains, and it had significantly less genes and smaller genomes when compared with other lactobacilli. Functional gene classification revealed that L. kunkeei had lost genes specifically involved in carbohydrate transport and metabolism. The species also lacked most of the genes for respiration, although growth was enhanced in the presence of oxygen. The adhE gene of L. kunkeei, encoding a bifunctional alcohol dehydrogenase (ADH)/aldehyde dehydrogenase (ALDH) protein, lacked the part encoding the ADH domain, which is reported here for the first time in lactic acid bacteria. The deletion resulted in the lack of ADH activity, implying a requirement for electron acceptors in glucose assimilation. These results clearly indicated that L. kunkeei had undergone a specific reductive evolution in order to adapt to fructose-rich environments. The reduction characteristics were similar to those of Fructobacillus spp., but distinct from other lactobacilli with small genomes, such as Lactobacillus gasseri and Lactobacillus vaginalis. Fructose-richness thus induced an environment-specific gene reduction in phylogenetically distant microorganisms.


Assuntos
Abelhas/microbiologia , Metabolismo dos Carboidratos/genética , Frutose/metabolismo , Genoma Bacteriano/genética , Lactobacillus/genética , Lactobacillus/metabolismo , Adaptação Fisiológica/genética , Álcool Desidrogenase/genética , Aldeído Oxirredutases/genética , Animais , DNA Bacteriano/genética , Lactobacillus/classificação , Lactobacillus/crescimento & desenvolvimento
18.
J Gen Appl Microbiol ; 62(2): 75-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27118075

RESUMO

To obtain lactic acid bacteria that scavenge environmental hydrogen peroxide, we developed a specialized enrichment medium and successfully isolated Pediococcus pentosaceus Be1 strain from a fermented food. This strain showed vigorous environmental hydrogen peroxide scavenging activity over a wide range of hydrogen peroxide concentrations. High Mn-catalase and NADH peroxidase activities were found in the cell-free extract of the P. pentosaceus Be1 strain, and these two hydrogen peroxide scavenging enzymes were purified from the cell-free extract of the strain. Mn-catalase has been purified from several microorganisms by several researchers, and the NADH peroxidase was first purified from the original strain in this report. After cloning the genes of the Mn-catalase and the NADH peroxidase, the deduced amino acid sequences were compared with those of known related enzymes.


Assuntos
Catalase/genética , Fermentação , Microbiologia de Alimentos , Peróxido de Hidrogênio/metabolismo , Pediococcus pentosaceus/isolamento & purificação , Pediococcus pentosaceus/metabolismo , Peroxidases/genética , Sequência de Aminoácidos , Catalase/química , Catalase/isolamento & purificação , Catalase/metabolismo , Clonagem Molecular , Meios de Cultura/química , Oryza/microbiologia , Oxirredução , Pediococcus pentosaceus/enzimologia , Pediococcus pentosaceus/genética , Peroxidases/química , Peroxidases/isolamento & purificação , Peroxidases/metabolismo , Raphanus/microbiologia , Verduras/microbiologia
19.
J Gen Appl Microbiol ; 62(2): 98-105, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27118078

RESUMO

Sirtuin is a protein with an enzymatic activity of NAD(+)-dependent protein deacetylation. It was first identified in yeast and its homologous genes have been widely found in various organisms. In bacteria, sirtuin gene was first described as cobB, encoding a cobalamin processing enzyme; and later its potential involvement in regulating acetylation levels of metabolic enzymes, transcription factors, chemotactic proteins and others have been reported. In order to study its physiological relevance in probiotic lactic acid bacteria, we analyzed the whole genome of three L. paracasei strains. All strains tested had sirtuin homolog genes designated hereby as sirA, and one of them had an additional gene designated as sirB. Following confirmation of their coding sequences by individual gene cloning, corresponding recombinant proteins have been generated and purified. The enzymatic characterization revealed that the intrinsic NAD(+)-dependent deacetylation activity of LpSirA (protein encoded by sirA) is comparable to human SIRT1. Furthermore, by blocking sirtuin activity using nicotinamide in vivo, together with an in vitro deacetylation reaction using recombinant LpSirA, we identified one of the target proteins in the lactic acid bacteria as the 30S ribosomal protein S4 (rpsD product).


Assuntos
Genoma Bacteriano , Lactobacillus paracasei/genética , Proteínas Ribossômicas/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Acetilação , Clonagem Molecular , Escherichia coli/genética , Humanos , Cinética , Lactobacillus paracasei/enzimologia , Lactobacillus paracasei/metabolismo , NAD/metabolismo , Fases de Leitura Aberta , Probióticos , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Ribossômicas/isolamento & purificação , Sirtuínas/química , Fatores de Transcrição/genética
20.
Int J Food Sci Nutr ; 67(2): 125-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26888650

RESUMO

Prebiotic oligosaccharides confer health benefits on the host by modulating the gut microbiota. Intestinal lactic acid bacteria (LAB) are potential targets of prebiotics; however, the metabolism of oligosaccharides by LAB has not been fully characterized. Here, we studied the metabolism of eight oligosaccharides by 19 strains of intestinal LAB. Among the eight oligosaccharides used, 1-kestose, lactosucrose and galactooligosaccharides (GOSs) led to the greatest increases in the numbers of the strains tested. However, mono- and disaccharides accounted for more than half of the GOSs used, and several strains only metabolized the mono- and di-saccharides in GOSs. End product profiles indicated that the amounts of lactate produced were generally consistent with the bacterial growth recorded. Oligosaccharide profiling revealed the interesting metabolic manner in Lactobacillus paracasei strains, which metabolized all oligosaccharides, but left sucrose when cultured with fructooligosaccharides. The present study clearly indicated that the prebiotic potential of each oligosaccharide differs.


Assuntos
Intestinos/microbiologia , Lactobacillus/fisiologia , Oligossacarídeos/metabolismo , Prebióticos , Fermentação
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