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Following identification of a target protein, hit identification, which finds small organic molecules that bind to the target, is an important first step of a structure-based drug design project. In this study, we demonstrate a target-specific drug design method that can autonomously generate a series of target-favorable compounds. This method utilizes the seq2seq model based on a deep learning algorithm and a water pharmacophore. Water pharmacophore models are used to screen compounds that are favorable to a given target in a large compound database, and seq2seq compound generators are used to train the screened compounds and generate entirely new compounds based on the training model. Our method was tested through binding energy calculation studies of six pharmaceutically relevant targets in the directory of useful decoys (DUD) set with docking. The compounds generated by our method had lower average binding energies than decoy compounds in five out of six cases and included a number of compounds that had lower binding energies than the average binding energies of the active compounds in four cases. The generated compound lists for these four cases featured compounds with lower binding energies than even the most active compounds.
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Aprendizaje Profundo , Diseño de Fármacos , Algoritmos , Ligandos , Simulación del Acoplamiento Molecular , Proteínas , AguaRESUMEN
Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation. Levels of leptin and adipokine were also improved and lipogenic and adipogenic genes in mesenteric fat and liver were down-regulated with XB supplementation. Furthermore, pro-inflammatory cytokines, fatty acid uptake, lipolysis, and ß-oxidation-related gene expression levels in mesenteric fat were down-regulated with XB supplementation. Thus, XB exhibited therapeutic potential for treating obesity which involved suppression of fat deposition and obesity-related metabolic disorders.
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Tejido Adiposo/metabolismo , Adiposidad/efectos de los fármacos , Disacáridos/farmacología , Disacáridos/uso terapéutico , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Tejido Adiposo/efectos de los fármacos , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Citocinas/metabolismo , Dieta Alta en Grasa , Ácidos Grasos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Lípidos/sangre , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Lipólisis/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/prevención & control , Tamaño de los Órganos/efectos de los fármacos , Oxidación-ReducciónRESUMEN
Purpose: To investigate the clinical features and visual outcome of infectious keratitis associated with Orthokeratology (Ortho-K) lens in Korean pediatric patients. Methods: We retrospectively reviewed medical records of patients diagnosed with Ortho-K lens-associated infectious keratitis from June 2005 to April 2020 at a tertiary referral hospital. Patients' demographics, clinical features, microbiological evaluation, and treatment methods were assessed and factors related to final visual outcomes were analyzed. Results: The study included 26 eyes of 26 patients (19 female, 7 male; mean age: 11.9 years), with an average Ortho-K lens wear duration of 33.7 ± 21.2 months. The highest number of cases occurred in summer (42.3%, 11/26). Central or paracentral corneal lesions were observed in 96.2% (25/26) of cases, with a mean corneal epithelial defect size of 5.13 mm². Pseudomonas aeruginosa was the most commonly isolated organism (n = 5), followed by Serratia marcescens (n = 4). All patients responded to medical treatment without needing surgical intervention. 72% of cases achieved favorable visual outcomes (Snellen BCVA > 6/12), while 8% experienced severe visual impairment (Snellen BCVA ≤ 6/60) due to residual central corneal opacities. Multivariable analysis showed that non-summer seasons, duration from symptom onset to presentation, and corneal epithelial defect size were significantly associated with final logMAR BCVA (p = 0.043, p = 0.040, and p = 0.002, respectively). Failed autorefraction at presentation due to an Ortho-K-related infectious keratitis lesion was a significant predictor of poor final visual outcome (Snellen BCVA ≤ 6/12) (OR = 38.995, p = 0.030). Conclusions: Ortho-K lens-related infectious keratitis can lead to permanent corneal opacities and potentially devastating visual outcomes in children. Delayed time to presentation, large corneal lesions, failure of autorefraction, and non-summer seasons were associated with poorer outcomes. Proper education and early detection would be key to safe use of orthokeratology lenses in pediatric patients.
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The emergence of multidrug-resistant pathogens has outpaced the development of new antibiotics, leading to renewed interest in endolysins. Endolysins have been investigated as novel biocontrol agents for Gram-positive bacteria. However, their efficacy against Gram-negative species is limited by the barrier presented by their outer membrane, which prevents endolysin access to the peptidoglycan substrate. Here, we used the translocation domain of botulinum neurotoxin to deliver endolysin across the outer membrane of Gram-negative bacteria. The translocation domain selectively interacts with and penetrates membranes composed of anionic lipids, which have been used in nature to deliver various proteins into animal cells. In addition to the botulinum neurotoxin translocation domain, we have fused bacteriophage-derived receptor binding protein to endolysins. This allows the attached protein to efficiently bind to a broad spectrum of Gram-negative bacteria. By attaching these target-binding and translocation machineries to endolysins, we aimed to develop an engineered endolysin with broad-spectrum targeting and enhanced antibacterial activity against Gram-negative species. To validate our strategy, we designed engineered endolysins using two well-known endolysins, T5 and LysPA26, and tested them against 23 strains from six species of Gram-negative bacteria, confirming that our machinery can act broadly. In particular, we observed a 2.32 log reduction in 30 min with only 0.5 µM against an Acinetobacter baumannii isolate. We also used the SpyTag/SpyCatcher system to easily attach target-binding proteins, thereby improving its target-binding ability. Overall, our newly developed endolysin engineering strategy may be a promising approach to control multidrug-resistant Gram-negative bacterial strains.
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Antibacterianos , Membrana Externa Bacteriana , Endopeptidasas , Bacterias Gramnegativas , Endopeptidasas/farmacología , Endopeptidasas/metabolismo , Endopeptidasas/química , Bacterias Gramnegativas/efectos de los fármacos , Antibacterianos/farmacología , Membrana Externa Bacteriana/efectos de los fármacos , Membrana Externa Bacteriana/metabolismo , Pruebas de Sensibilidad Microbiana , Transporte de Proteínas , Toxinas Botulínicas Tipo A/química , Toxinas Botulínicas Tipo A/metabolismo , Acinetobacter baumannii/efectos de los fármacosRESUMEN
The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.
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Enzima Convertidora de Angiotensina 2 , Anticuerpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animales , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Humanos , Ratones , COVID-19/virología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Antivirales/farmacología , Antivirales/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Chlorocebus aethiops , Células Vero , Internalización del Virus/efectos de los fármacos , Células HEK293 , Anticuerpos Antivirales/inmunologíaRESUMEN
Coffee waste is an abundant biomass that can be converted into high value chemical products, and is used in various renewable biological processes. In this study, oil was extracted from spent coffee grounds (SCGs) and used for polyhydroxyalkanoate (PHA) production through Pseudomonas resinovorans. The oil-extracted SCGs (OESCGs) were hydrolyzed and used for biohydrogen production through Clostridium butyricum DSM10702. The oil extraction yield through n-hexane was 14.4%, which accounted for 97% of the oil present in the SCGs. OESCG hydrolysate (OESCGH) had a sugar concentration of 32.26 g/L, which was 15.4% higher than that of the SCG hydrolysate (SCGH) (27.96 g/L). Hydrogen production using these substrates was 181.19 mL and 136.58 mL in OESCGH and SCGH media, respectively. The consumed sugar concentration was 6.77 g/L in OESCGH and 5.09 g/L in SCGH media. VFA production with OESCGH (3.58 g/L) increased by 40.9% compared with SCGH (2.54 g/L). In addition, in a fed-batch culture using the extracted oil, cell dry weight was 5.4 g/L, PHA was 1.6 g/L, and PHA contents were 29.5% at 24 h.
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Phasin is a surface-binding protein of polyhydroxyalkanoate (PHA) granules that is encoded by the phaP gene. As its expression increases, PHA granules become smaller, to increase their surface area, and are densely packed inside the cell, thereby increasing the PHA content. A wide range of PHA-producing bacteria have phaP genes; however, their PHA productivity differs, although they are derived from the cognate bacterial host cell. Modulating phasin expression could be a new strategy to enhance PHA production. This study aimed to characterize the effect of heterologous phasins on the reconstitution of E. coli BL21(DE3) and determine the best synergistic phaP gene combination to produce polyhydroxybutyrate (PHB). We identified novel phasins from a PHB high-producer strain, Halomonas sp. YLGW01, and introduced a combination of phaP genes into Escherichia coli. The resulting E. coli phaP1,3 strain had enhanced PHB production by 2.9-fold, leading to increased cell mass and increased PHB content from 48 % to 65 %. This strain also showed increased tolerance to inhibitors, such as furfural and vanillin, enabling the utilization of lignocellulose biosugar as a carbon source. These results suggested that the combination of phaP1 and phaP3 genes from H. sp. YLGW01 could increase PHB production and robustness.
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Escherichia coli , Lectinas de Plantas , Escherichia coli/genética , Escherichia coli/metabolismo , Lectinas de Plantas/metabolismo , Proteínas Bacterianas/química , Hidroxibutiratos/metabolismo , Poliésteres/metabolismoRESUMEN
Millimeter wave (MMW) imaging is finding rapid adoption in security applications such as concealed object detection under clothing. A passive MMW imaging system can operate as a stand-off type sensor that scans people in both indoors and outdoors. However, the imaging system often suffers from the diffraction limit and the low signal level. Therefore, suitable intelligent image processing algorithms would be required for automatic detection and recognition of the concealed objects. This paper proposes real-time outdoor concealed-object detection and recognition with a radiometric imaging system. The concealed object region is extracted by the multi-level segmentation. A novel approach is proposed to measure similarity between two binary images. Principal component analysis (PCA) regularizes the shape in terms of translation and rotation. A geometric-based feature vector is composed of shape descriptors, which can achieve scale and orientation-invariant and distortion-tolerant property. Class is decided by minimum Euclidean distance between normalized feature vectors. Experiments confirm that the proposed methods provide fast and reliable recognition of the concealed object carried by a moving human subject.
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Interpretación de Imagen Asistida por Computador/instrumentación , Interpretación de Imagen Asistida por Computador/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Radar/instrumentación , Imagen de Cuerpo Entero/instrumentación , Imagen de Cuerpo Entero/métodos , Diseño de Equipo , Análisis de Falla de Equipo , MicroondasRESUMEN
Millimeter wave imaging is finding rapid adoption in security applications such as the detection of objects concealed under clothing. A passive imaging system can be realized as a stand-off type sensor that can operate in open spaces, both indoors and outdoors. In this paper, we address real-time outdoor concealed-object detection and segmentation with a radiometric imaging system operating in the W-band. The imaging system is equipped with a dielectric lens and a receiver array operating at around 94 GHz. Images are analyzed by multilevel segmentation to identify a concealed object. Each level of segmentation comprises vector quantization, expectation-maximization, and Bayesian decision making to cluster pixels on the basis of a Gaussian mixture model. In addition, we describe a faster process that adopts only vector quantization for the first level segmentation. Experiments confirm that the proposed methods provide fast and reliable detection and segmentation for a moving human subject carrying a concealed gun.
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Monitoreo del Ambiente/instrumentación , Aumento de la Imagen/instrumentación , Interpretación de Imagen Asistida por Computador/instrumentación , Microondas , Sistemas de Computación , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
The protective effects of decursin (D) and decursinol angelate (DA) purified from Angelica gigas Nakai on amyloid ß-protein (Aß)-induced neurotoxicity and the underlying mechanisms were investigated. Aß plays a major role in the pathogenesis of Alzheimer's disease (AD) by eliciting oxidative stress. It significantly increased cytotoxicity and lipid peroxidation, but decreased glutathione contents and antioxidant enzyme activities. All of these results were markedly reversed by pretreatment with D or DA. Nuclear transcription factor Nrf2, which regulates the expression of antioxidant enzymes, was significantly increased by D or DA pretreatment. Furthermore, D and DA suppressed Aß aggregation. These results suggest that D and DA increase cellular resistance to Aß-induced oxidative injury in the rat pheochromocytoma (PC12) cells, presumably through not only the induction of Nrf2 and related antioxidant enzymes, but also the anti-aggregation of Aß. Thus D and DA have therapeutic potential in treating AD and other oxidative stress-related diseases.
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Péptidos beta-Amiloides/toxicidad , Antioxidantes/farmacología , Benzopiranos/farmacología , Butiratos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/fisiopatología , Angelica/química , Animales , Western Blotting , Catalasa/genética , Catalasa/metabolismo , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Factor 2 Relacionado con NF-E2/genética , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Nicolau syndrome (also known as embolia cutis medicamentosa and livedoid dermatitis) is a rare but severe localized adverse drug reaction of intramuscular injection of various drugs. The typical presentation is pain around the injection site soon after injection, followed by erythema, livedoid patch, hemorrhagic patch, and finally necrosis of skin, subcutaneous fat, and muscle tissue. We report a case that occurred in a 34-year-old woman after intramuscular injection of diclofenac sodium. Sonography showed diffuse thickening with increased echogenicity of the skin and subcutaneous fat layer, while MRI revealed extensive edema involving gluteal and piriformis muscles and deep fascia, and fluid collection.
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Antiinflamatorios no Esteroideos/efectos adversos , Diclofenaco/efectos adversos , Erupciones por Medicamentos/diagnóstico por imagen , Erupciones por Medicamentos/etiología , Inyecciones Intramusculares/efectos adversos , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Nalgas , Diclofenaco/administración & dosificación , Erupciones por Medicamentos/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética , Piel/diagnóstico por imagen , Piel/patología , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/patología , UltrasonografíaRESUMEN
An immunosuppressant tacrolimus-producing strain of Streptomyces sp. TST8 was isolated and developed by the TS corporation in Korea using the sequential adaptation of media containing tacrolimus (600-1600 mg/l). The aim of the tacrolimus sequential adaptation protocol was to select those cells with tacrolimus resistance and to reduce product inhibition of the tacrolimus-producing strain. The developed strains produced more tacrolimus than the original strain. In particular, the TST10 strain adapted in the medium containing 900 mg/l of tacrolimus produced 972 mg/l of tacrolimus in the final titer after 7 days of cultivation in a 5-l jar fermenter. This is the largest final titer of tacrolimus produced by a specific strain to date. Because the sequential adaptation protocol is limited by the solubility of tacrolimus in water, the final tacrolimus titer of TST11 adapted in the medium containing 1600 mg/l of tacrolimus was lower than that of TST10. The developed strains and the development method using sequential adaptation can facilitate the efficient and economical production of tacrolimus.
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Inmunosupresores/metabolismo , Microbiología Industrial , Streptomyces/aislamiento & purificación , Tacrolimus/metabolismo , Adaptación Fisiológica , Medios de Cultivo , Farmacorresistencia Bacteriana , Fermentación , Corea (Geográfico) , Pruebas de Sensibilidad Microbiana , Streptomyces/clasificación , Streptomyces/genética , Streptomyces/fisiologíaAsunto(s)
Hamartoma , Enfermedades del Aparato Lagrimal , Conducto Nasolagrimal , Humanos , Hamartoma/diagnóstico , Conducto Nasolagrimal/patología , Conducto Nasolagrimal/diagnóstico por imagen , Conducto Nasolagrimal/cirugía , Enfermedades del Aparato Lagrimal/diagnóstico , Enfermedades del Aparato Lagrimal/cirugía , Dacriocistorrinostomía/métodos , Masculino , Femenino , Enfermedades Raras , Obstrucción del Conducto Lagrimal/diagnósticoAsunto(s)
Endoftalmitis , Oftalmopatías , Infecciones Fúngicas del Ojo , Mucormicosis , Enfermedades Orbitales , Humanos , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/microbiología , Anfotericina B , Antifúngicos/uso terapéutico , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/microbiología , Enfermedades Orbitales/diagnóstico , Enfermedades Orbitales/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiologíaRESUMEN
Mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering, but their application has been impeded by lack of knowledge of their core biological properties. In order to identify MSC-specific proteins, the hydrophobic protein fraction was individually prepared from two different umbilical cord blood (UCB)-derived MSC populations; these were then subjected to two-dimensional (2D) gel electrophoresis and peptide mass fingerprinting matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)-mass spectrometry (MS). Although the 2D gel patterns differed somewhat between the two samples, computer-assisted image analysis identified shared protein spots. 35 spots were reliably identified corresponding to 32 different proteins, many of which were chaperones. Based on their primary sub-cellular locations the proteins could be grouped into 6 categories: extracellular, cell surface, endoplasmic reticular, mitochondrial, cytoplasmic and cytoskeletal proteins. This map of the water-insoluble proteome may provide valuable insights into the biology of the cell surface and other compartments of human MSCs.
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Sangre Fetal/citología , Células Madre Mesenquimatosas/química , Proteoma , Electroforesis en Gel Bidimensional , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Chaperonas Moleculares/análisis , Mapeo Peptídico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Fracciones Subcelulares/químicaRESUMEN
BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of D-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groups were maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ß-cells were analyzed. RESULTS: In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of D-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, D-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, D-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ß-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.
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Type 2 diabetes is a major public health concern worldwide. Xylobiose (XB) consists of two molecules of d-xylose and is a major disaccharide in xylooligosaccharides that are used as prebiotics. We hypothesized that XB could regulate diabetes-related metabolic and genetic changes via microRNA expression in db/db mice. For six weeks, C57BL/KsJ-db/db mice received 5% XB as part of the total sucrose content of their diet. XB supplementation improved glucose tolerance with reduced levels of OGTT AUC, fasting blood glucose, HbA1c, insulin, and HOMA-IR. Furthermore, XB supplementation decreased the levels of total triglycerides, total cholesterol, and LDL-C. The expression levels of miR-122a and miR-33a were higher and lower in the XB group, respectively. In the liver, expressions of the lipogenic genes, including, fatty acid synthase (FAS), peroxisome proliferator activated receptor γ (PPARγ), sterol regulatory element-binding protein-1C (SREBP-1C), sterol regulatory element-binding protein-2 (SREBP-2), acetyl-CoA carboxylase (ACC), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter G5/G8 (ABCG5/8), cholesterol 7 alpha-hydroxylase (CYP7A1), and sterol 12-alpha-hydroxylase (CYP8B1), as well as oxidative stress markers, including superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPX), and catalase, were also regulated by XB supplementation. XB supplementation inhibited the mRNA expressions levels of the pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1, as well as phosphorylation of c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK), p38 mitogen-activated protein kinases (MAPK), and extracellular signal-regulated kinases 1/2 (ERK1/2). These data demonstrate that XB exhibits anti-diabetic, hypolipogenic, and anti-inflammatory effects via regulation of the miR-122a/33a axis in db/db mice.
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Diabetes Mellitus Experimental/terapia , Disacáridos/administración & dosificación , Lipogénesis/fisiología , MicroARNs/metabolismo , Edulcorantes/administración & dosificación , Animales , Diabetes Mellitus Experimental/metabolismo , Suplementos Dietéticos , Lipogénesis/genética , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Prebióticos/administración & dosificaciónRESUMEN
Agricultural resources such as barley, wheat, and corn were hydrolyzed by commercial amylolytic enzymes and fermented into lactic acid by Enterococcus faecalis RKY1. Although no additional nutrients were supplemented to those resources, lactic acid productivities were obtained at >0.8 g/l h from barley and wheat. When 200 g/l of whole wheat flour was hydrolyzed by amylolytic enzymes after the pre-treatment with 0.3% (v/v) sulfuric acid and sterilized by filtration, E. faecalis RKY1 efficiently produced lactic acid with 2.6 g/l h of lactic acid productivity and 5.90 g/l of maximal dry cell weight without additional nutrients. Lactic acid productivity and cell growth could be enhanced to 31% and 12% higher values than those of non-adapted RKY1, by adaptation of E. faecalis RKY1 to CSL-based medium. When the medium contained 200 g/l of whole wheat flour hydrolyzate, 15 g/l of corn steep liquor, and 1.5 g/l of yeast extract, lactic acid productivity and maximal dry cell weight were obtained at 5.36 g/l h and 14.08 g/l, respectively. This result represented an improvement of up to 106% of lactic acid productivity and 138% of maximal dry cell weight in comparison to the fermentation from whole wheat flour hydrolyzate only.
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Reactores Biológicos , Grano Comestible/metabolismo , Enterococcus faecalis/enzimología , Ácido Láctico/biosíntesis , Cromatografía Líquida de Alta Presión , Fermentación , Hidrólisis , Ácidos SulfúricosRESUMEN
D-Xylose, a natural pentose, has been reported to reduce postprandial glucose levels, although its effect on lipid metabolism has not been investigated. Therefore, this study hypothesized that d-xylose, as an alternative sweetener, suppresses adipogenesis and lipid metabolism by regulating blood lipid profiles, blood glucose levels, and related gene expression in high-fat diet (HFD)-induced obese mice. Mice were fed a normal diet, a 60% HFD diet, or an HFD with 5% or 10% of the total sucrose content supplemented with d-xylose (Xylo 5 and Xylo 10 diets, respectively). Weight gain, food intake, and serum lipid levels for each group were measured. After 12 weeks, histopathology of liver sections and assays of gene expression related to adipogenesis and lipid metabolism in visceral fat and liver tissues were analyzed. Body weight gain; fasting blood glucose levels; weights of subcutaneous and visceral adipose tissues; and serum biochemical markers, including total cholesterol and low-density lipoprotein cholesterol, low-/high-density lipoprotein, and total cholesterol/high-density lipoprotein, were significantly lowered in the Xylo 5 and Xylo 10 groups. In addition, d-xylose supplementation resulted in the down-regulation of adipogenesis-related genes, including sterol regulatory element-binding protein 1C, fatty acid synthase, adipocyte protein 2, and CCAAT/enhancer-binding protein α in visceral adipose tissues. Histopathologically, Xylo 5 and Xylo 10 supplementation reduced HFD-induced fat accumulation in the liver and decreased expressions of fatty acid synthase and peroxisome proliferator-activated receptor γ. D-Xylose supplementation also enhanced lipid oxidation by increasing expressions of carnitine palmitoyltransferase 1A; cytochrome P450, family 4, subfamily a, polypeptide 10; and acyl-CoA oxidase. In conclusion, our finding suggests that d-xylose may help prevent or attenuate the progression of obesity-related metabolic disorders by alleviating adipogenesis and dyslipidemia and improving lipid oxidation.
Asunto(s)
Adipogénesis/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Suplementos Dietéticos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Obesidad , Xilosa/farmacología , Adipogénesis/genética , Tejido Adiposo/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Dieta Alta en Grasa/efectos adversos , Regulación hacia Abajo , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Dislipidemias/patología , Metabolismo de los Lípidos/genética , Lipólisis/efectos de los fármacos , Lipólisis/genética , Lipoproteínas/sangre , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/sangre , Obesidad/tratamiento farmacológico , Obesidad/etiología , Obesidad/genética , Edulcorantes/farmacología , Edulcorantes/uso terapéutico , Xilosa/uso terapéuticoRESUMEN
OBJECTIVE: The purpose of this study is to identify the risk factors associated with the development of germinal matrix-intraventricular hemorrhage (GM-IVH) and the relationship of the severity of disease and prematurity. METHODS: A total of 168 premature neonates whose birth weight ≤1500 g or gestational age ≤34 weeks were examined by cranial ultrasound (CUS) for detection of GM-IVH among the babies admitted between January 2011 and December 2012 in our medical center neonatal intensive care unit. The babies were divided into two groups : GM-IVH and non-IVH. Clinical presentations, precipitating factors of the patients and maternal factors were analyzed. RESULTS: In univariate analysis, gestational age, birth weight, delivery method, presence of premature rupture of membrane (PROM) and level of sodium and glucose were statistically meaningful factors (p<0.05). But only two factors, gestational age and presence of patent ductus arteriosus (PDA) were statistically meaningful in multivariate logistic regression (p<0.05). Delivery method [normal vaginal delivery (NVD) to Caeserean section] was borderline significant (p<0.10). CONCLUSION: Presence of PDA and gestational age were the important risk factors associated with development of GM-IVH.