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1.
Front Mol Neurosci ; 16: 1163447, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465366

RESUMEN

Many Alzheimer's disease (AD) patients suffer from altered cerebral blood flow and damaged cerebral vasculature. Cerebrovascular dysfunction could play an important role in this disease. However, the mechanism underlying a vascular contribution in AD is still unclear. Cerebrovascular reactivity (CVR) is a critical mechanism that maintains cerebral blood flow and brain homeostasis. Most current methods to analyze CVR require anesthesia which is known to hamper the investigation of molecular mechanisms underlying CVR. We therefore combined spectroscopy, spectral analysis software, and an implantable device to measure cerebral blood volume fraction (CBVF) and oxygen saturation (SO2) in unanesthetized, freely-moving mice. Then, we analyzed basal CBVF and SO2, and CVR of 5-month-old C57BL/6 mice during hypercapnia as well as during basic behavior such as grooming, walking and running. Moreover, we analyzed the CVR of freely-moving AD mice and their wildtype (WT) littermates during hypercapnia and could find impaired CVR in AD mice compared to WT littermates. Our results suggest that this optomechanical approach to reproducibly getting light into the brain enabled us to successfully measure CVR in unanesthetized freely-moving mice and to find impaired CVR in a mouse model of AD.

2.
Front Aging Neurosci ; 15: 1064178, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36967821

RESUMEN

Introduction: Alzheimer's Disease (AD) patients exhibit signs of motor dysfunction, including gait, locomotion, and balance deficits. Changes in motor function often precede other symptoms of AD as well as correlate with increased severity and mortality. Despite the frequent occurrence of motor dysfunction in AD patients, little is known about the mechanisms by which this behavior is altered. Methods and Results: In the present study, we investigated the relationship between cerebrovascular impairment and motor dysfunction in a mouse model of AD (Tg6799). We found an age-dependent increase of extravasated fibrinogen deposits in the cortex and striatum of AD mice. Interestingly, there was significantly decreased cerebrovascular density in the striatum of the 15-month-old as compared to 7-month-old AD mice. We also found significant demyelination and axonal damage in the striatum of aged AD mice. We analyzed striatum-related motor function and anxiety levels of AD mice at both ages and found that aged AD mice exhibited significant impairment of motor function but not in the younger AD mice. Discussion: Our finding suggests an enticing correlation between extravasated fibrinogen, cerebrovascular damage of the striatum, and motor dysfunction in an AD mouse model, suggesting a possible mechanism underlying motor dysfunction in AD.

3.
Clin Gastroenterol Hepatol ; 20(5): e1022-e1039, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34216823

RESUMEN

BACKGROUND & AIMS: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD). METHODS: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871). RESULTS: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities. CONCLUSIONS: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Fracturas de Cadera , Enfermedades Inflamatorias del Intestino , Corticoesteroides , Estudios de Casos y Controles , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/epidemiología , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Factores de Riesgo
4.
Neurobiol Aging ; 107: 96-108, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34416494

RESUMEN

Vascular perturbations and cerebral hypometabolism are emerging as important components of Alzheimer's disease (AD). While various in vivo imaging modalities have been designed to detect changes of cerebral perfusion and metabolism in AD patients and animal models, study results were often heterogenous with respect to imaging techniques and animal models. We therefore evaluated cerebral perfusion and glucose metabolism of two popular transgenic AD mouse strains, TgCRND8 and 5xFAD, at 7 and 12 months-of-age under identical conditions and analyzed possible molecular mechanisms underlying heterogeneous cerebrovascular phenotypes. Results revealed disparate findings in these two strains, displaying important aspects of AD progression. TgCRND8 mice showed significantly decreased cerebral blood flow and glucose metabolism with unchanged cerebral blood volume (CBV) at 12 months-of-age whereas 5xFAD mice showed unaltered glucose metabolism with significant increase in CBV at 12 months-of-age and a biphasic pattern of early hypoperfusion followed by a rebound to normal cerebral blood flow in late disease. Finally, immunoblotting assays suggested that VEGF dependent vascular tone change may restore normoperfusion and increase CBV in 5xFAD.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Circulación Cerebrovascular , Modelos Animales de Enfermedad , Glucosa/metabolismo , Humanos , Ratones Transgénicos
5.
Foods ; 9(7)2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32630165

RESUMEN

The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. Monascus pigments, widely used as food additives, can be used as a chronic inflammation treatment. Orange Monascus pigments were produced by submerged fermentation in a 5 L bioreactor, and multiple orange Monascus pigment derivatives with anti-inflammatory activities were synthesized using aminophilic reaction. A total of 41 types of pigment derivatives were produced by incorporating amines and amino acids into the orange pigments. One derivative candidate that inhibited nitric oxide (NO) production in Raw 264.7 cells and exhibited low cell cytotoxicity was identified via in vitro assay. The 2-amino-4 picoline derivative inhibited NO production of 48.4%, and exhibited cell viability of 90.6%. Expression of inducible NO synthase, an important enzyme in the NO synthesis pathway, was suppressed by such a derivative in a dose-dependent manner. Therefore, this derivative has potential as a functional food colorant with anti-inflammatory effects.

6.
Proc Natl Acad Sci U S A ; 117(25): 14482-14492, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32518112

RESUMEN

Cerebral amyloid angiopathy (CAA), where beta-amyloid (Aß) deposits around cerebral blood vessels, is a major contributor of vascular dysfunction in Alzheimer's disease (AD) patients. However, the molecular mechanism underlying CAA formation and CAA-induced cerebrovascular pathology is unclear. Hereditary cerebral amyloid angiopathy (HCAA) is a rare familial form of CAA in which mutations within the (Aß) peptide cause an increase in vascular deposits. Since the interaction between Aß and fibrinogen increases CAA and plays an important role in cerebrovascular damage in AD, we investigated the role of the Aß-fibrinogen interaction in HCAA pathology. Our work revealed the most common forms of HCAA-linked mutations, Dutch (E22Q) and Iowa (D23N), resulted in up to a 50-fold stronger binding affinity of Aß for fibrinogen. In addition, the stronger interaction between fibrinogen and mutant Aßs led to a dramatic perturbation of clot structure and delayed fibrinolysis. Immunofluorescence analysis of the occipital cortex showed an increase of fibrin(ogen)/Aß codeposition, as well as fibrin deposits in HCAA patients, compared to early-onset AD patients and nondemented individuals. Our results suggest the HCAA-type Dutch and Iowa mutations increase the interaction between fibrinogen and Aß, which might be central to cerebrovascular pathologies observed in HCAA.


Asunto(s)
Péptidos beta-Amiloides/genética , Encéfalo/patología , Angiopatía Amiloide Cerebral Familiar/patología , Fibrina/metabolismo , Fibrinógeno/metabolismo , Fragmentos de Péptidos/genética , Péptidos beta-Amiloides/metabolismo , Angiopatía Amiloide Cerebral Familiar/genética , Femenino , Fibrinógeno/aislamiento & purificación , Fibrinólisis/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fragmentos de Péptidos/metabolismo , Unión Proteica/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo
7.
RSC Adv ; 10(9): 5339-5350, 2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35498283

RESUMEN

Salicornia herbacea (glasswort) is a traditional Asian medicinal plant which exhibits multiple nutraceutical and pharmaceutical properties. Quercetin-3-glucoside and isorhamnetin-3-glucoside are the major flavonoid glycosides found in S. herbacea. Multiple researchers have shown that flavonoid glycosides can be structurally transformed into minor aglycone molecules, which play a significant role in exerting physiological responses in vivo. However, minor aglycone molecule levels in S. herbacea are very low. In this study, Bifidobacterium animalis subsp. lactis AD011, isolated from infant feces, catalyzed >85% of quercetin-3-glucoside and isorhamnetin-3-glucoside into quercetin and isorhamnetin, respectively, in 2 h, without breaking down flavonoid backbones. Functionality analysis demonstrated that the quercetin and isorhamnetin produced showed improved anti-inflammatory activity vs. the original source molecules against lipopolysaccharide induced RAW 264.7 macrophages. Our report highlights a novel protocol for rapid quercetin and isorhamnetin production from S. herbacea flavonoids and the applicability of quercetin and isorhamnetin as nutraceutical molecules with enhanced anti-inflammatory properties.

8.
Neuron ; 101(6): 991-993, 2019 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-30897363

RESUMEN

Exactly how cerebrovascular alterations contribute to Alzheimer's disease (AD) is still unknown. Merlini et al. (2019) show that blood-derived fibrinogen leads to dendritic spine elimination and cognitive deficit via microglial CD11b/CD18. Fibrinogen may be a significant contributor to AD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Encéfalo , Fibrinógeno , Humanos , Microglía
9.
J Vis Exp ; (141)2018 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-30582601

RESUMEN

This article presents methods for generating in vitro fibrin clots and analyzing the effect of beta-amyloid (Aß) protein on clot formation and structure by spectrometry and scanning electron microscopy (SEM). Aß, which forms neurotoxic amyloid aggregates in Alzheimer's disease (AD), has been shown to interact with fibrinogen. This Aß-fibrinogen interaction makes the fibrin clot structurally abnormal and resistant to fibrinolysis. Aß-induced abnormalities in fibrin clotting may also contribute to cerebrovascular aspects of the AD pathology such as microinfarcts, inflammation, as well as, cerebral amyloid angiopathy (CAA). Given the potentially critical role of neurovascular deficits in AD pathology, developing compounds which can inhibit or lessen the Aß-fibrinogen interaction has promising therapeutic value. In vitro methods by which fibrin clot formation can be easily and systematically assessed are potentially useful tools for developing therapeutic compounds. Presented here is an optimized protocol for in vitro generation of the fibrin clot, as well as analysis of the effect of Aß and Aß-fibrinogen interaction inhibitors. The clot turbidity assay is rapid, highly reproducible and can be used to test multiple conditions simultaneously, allowing for the screening of large numbers of Aß-fibrinogen inhibitors. Hit compounds from this screening can be further evaluated for their ability to ameliorate Aß-induced structural abnormalities of the fibrin clot architecture using SEM. The effectiveness of these optimized protocols is demonstrated here using TDI-2760, a recently identified Aß-fibrinogen interaction inhibitor.


Asunto(s)
Péptidos beta-Amiloides/efectos adversos , Fibrina/metabolismo , Microscopía Electrónica de Rastreo/métodos , Análisis Espectral/métodos , Fibrina/análisis , Humanos
10.
Int J Mol Sci ; 19(9)2018 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-30205574

RESUMEN

Platycodi radix (i.e., Platycodon grandiflorum root) products (e.g., tea, cosmetics, and herbal supplements) are popular in East Asian nutraceutical markets due to their reported health benefits and positive consumer perceptions. Platycosides are the key drivers of Platycodi radixes' biofunctional effects; their nutraceutical and pharmaceutical activities are primarily related to the number and varieties of sugar side-chains. Among the various platycosides, platycodin D is a major saponin that demonstrates various nutraceutical activities. Therefore, the development of a novel technology to increase the total platycodin D content in Platycodi radix extract is important, not only for consumers' health benefits but also producers' commercial applications and manufacturing cost reduction. It has been reported that hydrolysis of platycoside sugar moieties significantly modifies the compound's biofunctionality. Platycodi radix extract naturally contains two major platycodin D precursors (platycoside E and platycodin D3) which can be enzymatically converted to platycodin D via ß-d-glucosidase hydrolysis. Despite evidence that platycodin D precursors can be changed to platycodin D in the Platycodi radix plant, there is little research on increasing platycodin D concentrations during processing. In this work, platycodin D levels in Platycodi radix extracts were significantly increased via extracellular Aspergillus usamii ß-d-glucosidase (n = 3, p < 0.001). To increase the extracellular ß-d-glucosidase activity, A. usamii was cultivated in a culture media containing cellobiose as its major carbon source. The optimal pH and temperature of the fungal ß-d-glucosidase were 6.0 and 40.0 °C, respectively. Extracellular A. usamii ß-d-glucosidase successfully converted more than 99.9% (w/v, n = 3, p < 0.001) of platycoside E and platycodin D3 into platycodin D within 2 h under optimal conditions. The maximum level of platycodin D was 0.4 mM. Following the biotransformation process, the platycodin D was recovered using preparatory High Performance Liquid Chromatography (HPLC) and applied to in vitro assays to evaluate its quality. Platycodin D separated from the Platycodi radix immediately following the bioconversion process showed significant anti-inflammatory effects from the Lipopolysaccharide (LPS)-induced macrophage inflammatory responses with decreased nitrite and IL-6 production (n = 3, p < 0.001). Taken together, these results provide evidence that biocatalysis of Platycodi radix extracts with A. usamii may be used as an efficient method of platycodin D-enriched extract production and novel Platycodi radix products may thereby be created.


Asunto(s)
Aspergillus/enzimología , Ácido Oleanólico/análogos & derivados , Platycodon/metabolismo , Saponinas/metabolismo , Triterpenos/metabolismo , beta-Glucosidasa/metabolismo , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Biocatálisis , Biotecnología/métodos , Biotransformación , Interleucina-6/inmunología , Lipopolisacáridos/inmunología , Ratones , Ácido Oleanólico/metabolismo , Células RAW 264.7 , Saponinas/farmacología , Triterpenos/farmacología
11.
Biochemistry ; 57(8): 1399-1409, 2018 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-29394041

RESUMEN

Accumulating evidence suggests that fibrinogen, a key protein in the coagulation cascade, plays an important role in circulatory dysfunction in Alzheimer's disease (AD). Previous work has shown that the interaction between fibrinogen and ß-amyloid (Aß), a hallmark pathological protein in AD, induces plasmin-resistant abnormal blood clots, delays fibrinolysis, increases inflammation, and aggravates cognitive function in mouse models of AD. Since Aß oligomers have a much stronger affinity for fibrinogen than Aß monomers, we tested whether amyloid aggregation inhibitors could block the Aß-fibrinogen interaction and found that some Aß aggregation inhibitors showed moderate inhibitory efficacy against this interaction. We then modified a hit compound so that it not only showed a strong inhibitory efficacy toward the Aß-fibrinogen interaction but also retained its potency toward the Aß42 aggregation inhibition process. Furthermore, our best hit compound, TDI-2760, modulated Aß42-induced contact system activation, a pathological condition observed in some AD patients, in addition to inhibiting the Aß-fibrinogen interaction and Aß aggregation. Thus, TDI-2760 has the potential to lessen vascular abnormalities as well as Aß aggregation-driven pathology in AD.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Fibrinógeno/metabolismo , Fragmentos de Péptidos/metabolismo , Agregado de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Pirimidinas/química , Pirimidinas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Diseño de Fármacos , Humanos , Agregación Patológica de Proteínas/tratamiento farmacológico , Agregación Patológica de Proteínas/metabolismo
12.
Ann Dermatol ; 29(5): 586-596, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28966515

RESUMEN

BACKGROUND: To meet the need for a subspecialized skin type system, the Baumann skin type (BST) system was proposed. OBJECTIVE: To evaluate the distribution of BST types and influencing factors among Korean women. METHODS: BST questionnaires were administered to 1,000 Korean women. The possible responses were as follows: oily (O) or dry (D), sensitive (S) or resistant (R), pigmented (P) or non-pigmented (N), and wrinkled (W) or tight (T). The correlations of the BST with the subjects' age, location, ultraviolet (UV) ray exposure, drinking and smoking habits, and blood type were assessed. RESULTS: The OSNT, DSNT, DRNT, and OSNW skin types were the most common skin types (55.3%). The O, S, P, and W types accounted for 46.6%, 68.8%, 23.2%, and 31.9%, respectively. The proportion of the O and S type was the highest in Gyeongsangbuk-do (55.0%) and Seoul (77.2%). The proportion of the P and W type was the highest in Gyeongsangbuk-do (33.0%) and Chungcheong-do (39.0%). The O type decreased in the higher age group, whereas the P and W type showed a reversed tendency. In smokers, the proportion of W type was significantly higher than in the non-smokers (66.3% vs. 24.1%, p<0.05). CONCLUSION: The 4 most common BST types were OSNT, DSNT, DRNT, and OSNW. In the comparison across the 4 BST parameters according to the age, region, smoking and drinking habits, occupation, blood type, and UV exposure, significant differences were observed. Individualized and customized skin care is required according to the personal skin type.

13.
Biol Pharm Bull ; 39(9): 1461-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27582326

RESUMEN

To transform ginsenosides, Korean ginseng berry (KGB) was fermented by mycotoxin non-producing Aspergillus niger and Aspergillus oryzae. Changes of ginsenoside profile and anti-proliferative activities were observed. Results showed that A. niger tended to efficiently transform protopanaxadiol (PPD) type ginsenosides such as Rb1, Rb2, Rd to compound K while A. oryzae tended to efficiently transform protopanaxatriol (PPT) type ginsenoside Re to Rh1 via Rg1. Butanol extracts of fermented KGB showed high cytotoxicity on human adenocarcinoma HT-29 cell line and hepatocellular carcinoma HepG2 cell line while that of unfermented KGB showed little. The minimum effective concentration of niger-fermented KGB was less than 2.5 µg/mL while that of oryzae-fermented KGB was about 5 µg/mL. As A. niger is more inclined to transform PPD type ginsenosides, niger-fermented KGB showed stronger anti-proliferative activity than oryzae-fermented KGB.


Asunto(s)
Aspergillus niger/metabolismo , Aspergillus oryzae/metabolismo , Frutas/química , Ginsenósidos/análisis , Panax , Extractos Vegetales/metabolismo , Proliferación Celular/efectos de los fármacos , Fermentación , Ginsenósidos/metabolismo , Células HT29 , Células Hep G2 , Humanos , Micotoxinas , Extractos Vegetales/química , Extractos Vegetales/farmacología
14.
Blood ; 128(8): 1144-51, 2016 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-27389717

RESUMEN

The majority of patients with Alzheimer disease (AD) suffer from impaired cerebral circulation. Accumulating evidence suggests that fibrinogen, the main protein component of blood clots, plays an important role in this circulatory dysfunction in AD. Fibrinogen interacts with ß-amyloid (Aß), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition is found in the brains of AD patients and mouse models. In this study, we investigated the biochemical and structural details of the Aß-fibrinogen interaction. We identified the central region of Aß42 as the most critical region for the interaction, which can be inhibited by specific antibodies against the central region of Aß and by naturally occurring p3 peptides, Aß17-40 and Aß17-42. X-ray crystallographic analysis revealed that Aß42 binding to fragment D of fibrinogen induced a structural change in the C-terminal region of the fibrinogen ß-chain (ß384-393). Furthermore, we identified an additional Aß-binding site within the αC region of fibrinogen. Aß binding to this αC region blocked plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of a plasmin-resistant fibrin degradation fragment. Overall, our study elucidates the Aß-fibrinogen interaction and clarifies the mechanism by which Aß-fibrinogen binding delays fibrinolysis by plasmin. These results may facilitate the development of effective therapeutics against the Aß-fibrinogen interaction to treat cerebrovascular abnormalities in AD.


Asunto(s)
Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Fibrinógeno/química , Fibrinógeno/metabolismo , Secuencia de Aminoácidos , Animales , Anticuerpos/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/química , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinolisina/metabolismo , Fibrinólisis , Humanos , Ratones , Unión Proteica , Dodecil Sulfato de Sodio/metabolismo
15.
J Microbiol Biotechnol ; 25(8): 1315-20, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25876604

RESUMEN

To enhance the γ-aminobutyric acid (GABA) content, the optimized fermentation of soybean with added sea tangle extract was evaluated at 30°C and pH 5.0. The medium was first inoculated with Aspergillus oryzae strain FMB S46471 and fermented for 3 days, followed by the subsequent inoculation with Lactobacillus brevis GABA 100. After fermentation for 7 days, the fermented soybean showed approximately 1.9 g/kg GABA and exhibited higher ACE inhibitory activity than the traditional soybean product. Furthermore, several peptides in the fraction containing the highest ACE inhibitory activity were identified. The novel fermented soybean enriched with GABA and ACE inhibitory components has great pharmaceutical and functional food values.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Aspergillus oryzae/metabolismo , Glycine max/metabolismo , Kelp/metabolismo , Levilactobacillus brevis/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Aspergillus oryzae/crecimiento & desarrollo , Técnicas de Cocultivo , Fermentación , Concentración de Iones de Hidrógeno , Levilactobacillus brevis/crecimiento & desarrollo , Temperatura
16.
J Microbiol Biotechnol ; 25(4): 469-78, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25348696

RESUMEN

In spite of the reported probiotic effects, Bifidobacterium bifidum BGN4 (BGN4) showed no ß- glucosidase activity and failed to biotransform isoflavone glucosides into the more bioactive aglycones during soy milk fermentation. To develop an isoflavone-biotransforming BGN4, we constructed the recombinant B. bifidum BGN4 strain (B919G) by cloning the structural ß- glucosidase gene from B. lactis AD011 (AD011) using the expression vector with the constitutively active promoter 919 from BGN4. As a result, B919G highly expressed ß- glucosidase and showed higher ß-glucosidase activity and heat stability than the source strain of the ß-glucosidase gene, AD011. The biotransformation of daidzin and genistin compounds using the crude enzyme extract from B919G was completed within 4 h, and the bioconversion of daidzin and genistin in soy milk during fermentation with B919G also occurred within 6 h, which was much faster and higher than with AD011. The incorporation of this ß-glucosidaseproducing Bifidobacterium strain in soy milk could lead to the production of fermented soy milk with an elevated amount of bioavailable forms of isoflavones as well as to the indigenous probiotic effects of the Bifidobacterium strain.


Asunto(s)
Bifidobacterium/genética , Bifidobacterium/metabolismo , Fermentación , Glucósidos/metabolismo , Isoflavonas/metabolismo , Leche de Soja/metabolismo , beta-Glucosidasa/genética , beta-Glucosidasa/metabolismo , Biotransformación , Estabilidad de Enzimas , Expresión Génica , Viabilidad Microbiana
17.
Asian-Australas J Anim Sci ; 27(3): 383-90, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25049965

RESUMEN

A 15-wk feeding trial was conducted to examine the supplemental effects of Barodon on growth performance, gastrointestinal histology, feed digestibility and innate immunity in olive founder. A basal commercial diet was used as a control and two other diets were prepared by spraying 0.1% or 0.2% of Barodon. Triplicate groups of fish (BW, 145 g) were fed one of the test diets to apparent satiation twice daily. At the end of the feeding trial, fish growth performance was not significantly affected by dietary treatments; however, feed utilization was significantly improved (linear and quadratic, p<0.05) by Barodon supplementation. Significantly higher (p<0.05) survival rates were obtained in fish fed Barodon containing diets. Hepatosomatic index increased significantly in Barodon treated groups. Also, the use of Barodon resulted in significant increase (linear and quadratic, p<0.05) of intestine length and number of goblet cells. Significantly higher (Quadratic, p<0.05) apparent digestibility coefficient of DM was obtained by supplementation of Barodon. Lysozyme and myeloperoxidase activities increased quadratically and linearly, respectively, in Barodon treated fish. Also, significantly higher (linear and quadratic, p<0.05) superoxide dismutase activity was found in Barodon fed fish. The findings in this study show that inclusion of Barodon in diets for olive flounder improves feed utilization and digestibility, and positively affects digestive tract histology and innate immunity.

18.
J Exp Med ; 211(6): 1049-62, 2014 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-24821909

RESUMEN

Many Alzheimer's disease (AD) patients suffer from cerebrovascular abnormalities such as altered cerebral blood flow and cerebral microinfarcts. Recently, fibrinogen has been identified as a strong cerebrovascular risk factor in AD, as it specifically binds to ß-amyloid (Aß), thereby altering fibrin clot structure and delaying clot degradation. To determine if the Aß-fibrinogen interaction could be targeted as a potential new treatment for AD, we designed a high-throughput screen and identified RU-505 as an effective inhibitor of the Aß-fibrinogen interaction. RU-505 restored Aß-induced altered fibrin clot formation and degradation in vitro and inhibited vessel occlusion in AD transgenic mice. Furthermore, long-term treatment of RU-505 significantly reduced vascular amyloid deposition and microgliosis in the cortex and improved cognitive impairment in mouse models of AD. Our studies suggest that inhibitors targeting the Aß-fibrinogen interaction show promise as therapy for treating AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Trastornos del Conocimiento/prevención & control , Fibrinógeno/metabolismo , Pirazoles/farmacología , Pirimidinas/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Trombosis/prevención & control , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Humanos , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Fluorescente , Estructura Molecular , Actividad Motora/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Pirazoles/química , Pirimidinas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacocinética , Imagen de Lapso de Tiempo/métodos
19.
J Alzheimers Dis ; 32(3): 599-608, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22869464

RESUMEN

Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) plaques, tau tangles, brain atrophy, and vascular pathology. Vascular defects include cerebrovascular dysfunction, decreased cerebral blood flow, and blood brain barrier (BBB) disruption, among others. Here, we review the evidence that links Aß with the vascular pathology present in AD, with a specific focus on the hemostatic system and the clotting protein fibrinogen. Fibrinogen is normally found circulating in blood, but in AD it deposits with Aß in the brain parenchyma and cerebral blood vessels. We found that Aß and fibrin(ogen) interact, and their binding leads to increased fibrinogen aggregation, Aß fibrillization, and the formation of degradation-resistant fibrin clots. Decreasing fibrinogen levels not only lessens cerebral amyloid angiopathy and BBB permeability, but it also reduces microglial activation and improves cognitive performance in AD mouse models. Moreover, a prothrombotic state in AD is evidenced by increased clot formation, decreased fibrinolysis, and elevated levels of coagulation factors and activated platelets. Abnormal deposition and persistence of fibrin(ogen) in AD may result from Aß-fibrin(ogen) binding and altered hemostasis and could thus contribute to Aß deposition, decreased cerebral blood flow, exacerbated neuroinflammation, and eventual neurodegeneration. Blocking the interaction between fibrin(ogen) and Aß may be a promising therapeutic target for AD.


Asunto(s)
Enfermedad de Alzheimer/sangre , Circulación Cerebrovascular/fisiología , Fibrinógeno/metabolismo , Hemostasis/fisiología , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/terapia , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Humanos
20.
Int J Food Microbiol ; 157(1): 65-72, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22564451

RESUMEN

Bifidobacterium adolescentis Int57 (Int57) and Propionibacterium freudenreichii subsp. shermanii ATCC 13673 (ATCC 13673) were grown either in coculture or as pure cultures in different media, such as cow's milk, soybean milk, and modified MRS medium. The viable cell counts of bacteria, changes in pH, concentrations of organic acids, and contents of various sugars were analyzed during incubation up to 7days. In soy milk, the survival of cocultured Int57 was six times higher than the monocultured cells, and ATCC 13673 cocultured with Int57 consumed 69.4% of lactic acid produced by Int57 at the end of fermentation. In cow's milk, coculture with ATCC 13673 increased the growth of Int57 from 24h until 120h by approximately tenfold and did not affect the survival of Int57 cells. After 96h of fermentation of modified MRS, the survival of ATCC 13673 cells cocultured with Int57 increased by 3.2- to 7.4-folds as compared with ATCC 13673 monoculture, whereas the growth of Int57 cells was unaffected. The growth and metabolic patterns of two strains during coculture showed noticeable differences between food grade media and laboratory media. The consumption of stachyose in soy milk during coculture of Int57 with ATCC 13673 was increased by more than twice compared with Int57 monoculture, and completed within 24h. The combinational use of Bifidobacterium and Propionibacterium could be applied to the development of fermented milk or soy milk products.


Asunto(s)
Bifidobacterium/crecimiento & desarrollo , Productos Lácteos/microbiología , Leche/microbiología , Propionibacterium/crecimiento & desarrollo , Animales , Bifidobacterium/metabolismo , Carbohidratos/análisis , Bovinos , Técnicas de Cocultivo , Femenino , Fermentación , Concentración de Iones de Hidrógeno , Ácido Láctico/metabolismo , Propionibacterium/metabolismo , Leche de Soja
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