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Urine organic acid contains water-soluble metabolites and/or metabolitesderived from sugars, amino acids, lipids, vitamins, and drugswhich can reveal a human's physiological condition. These urine organic acidshippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acidwere the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography−tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine. Stable-labeled isotope standard (creatinine-d3) and acetonitrile were added to the urine sample. The supernatant was diluted with deionized water and injected into LC-MS/MS. This method was validated with high selectivity for the urine sample, a low limit of quantification (10−40 ng/mL), good linearity (r > 0.995), high accuracy (85.8−109.7%), and high precision (1.4−13.3%). This method simultaneously analyzed creatinine in urine, which calibrates metabolic rate between different individuals. Validation has been completed for this method; as such, it could possibly be applied to the study of gut microbiota clinically.
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Microbioma Gastrointestinal , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Creatinina , Disbiose , Humanos , Compostos Orgânicos , Espectrometria de Massas em Tandem/métodos , ÁguaRESUMO
Sweet potato (Ipomoea batatas L.) is one of the most important food crops worldwide, with leaves of different varieties showing purple, green and yellow, and these leaves provide a dietary source of nutrients and various bioactive compounds. The objective of this study was to identify the active constituents of chlorogenic acids (CGAs) in different methanolic extract of leaves of three varieties of sweet potato (purple CYY 98-59, green Taoyuan 2, and yellow CN 1927-16) using liquid chromatography-tandem mass spectrometry. Genotype-specific metabolite variations were observed; CGAs and three isomeric peaks were detected in sweet potato leaf extracts (SPLEs). Among them, the yellow SPLE contained the highest contents of 3,5-dicaffeoylquinic acid (3,5-di-CQA) and 3,4-dicaffeoylquinic acid (3,4-di-CQA), followed by the green SPLE, whereas the purple SPLE retained lower 3,5-di-CQA content compared to yellow and green SPLEs. All three SPLEs contained lower 4,5-dicaffeoylquinic acid (4,5-di-CQA) and CGA contents compared to 3,5-di-CQA and 3,4-di-CQA, although CGA constituents were not significantly different in genotypes, whereas purple SPLE contained higher 4,5-di-CQA content compared to yellow and green SPLEs. This study indicates that SPLs marketed in Taiwan vary widely in their biological potentials and may impart different health benefits to consumers.
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Background: Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. Methods: This prospective observational cohort study enrolled 261 patients with CKD stages 1−5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. Results: The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (ß ± SE: 24.298 ± 8.616, p = 0.005; 60.316 ± 21.875, p = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both p < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, p = 0.019). Conclusion: Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival.
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Falência Renal Crônica , Insuficiência Renal Crônica , Selênio , Humanos , Rim/fisiologia , Micronutrientes , Estudos Prospectivos , Insuficiência Renal Crônica/complicaçõesRESUMO
Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. The TFPS exhibited high uronic acid content and high viscosity in water. The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. In addition, TFPS exhibited the inhibition of cholesterol micelles in vitro in a concentration-dependent manner. In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS.
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Cucurbitane-type triterpenoids are a major class of bioactive compounds present in bitter melon. In the present study, six different cultivars of bitter melon were extracted by using microwave- or ultrasound-assisted techniques to identify the prominent method that can extract the majority of cucurbitane-type triterpenoids. A UHPLC-MS/MS (ultra-high-performance liquid chromatography tandem mass spectrometry) system was used for the identification and quantification of ten cucurbitane-type triterpenoids. The results suggest that the use of microwave-assisted extraction on cultivars 4 and 5 produced higher amounts of the selected cucurbitane-type triterpenoids. The interpretation of principal component analysis also identified that cultivar 4 is significantly different from the others in which the compounds 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al and momordicine I were found in higher quantities. Upon further evaluation, it was also identified that these two triterpenoids can act as antiproliferative agents due to their effects on SAS human oral cancer cell lines.
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Major anthocyanin, cyanidin-3-sophoroside (318.1 mg/mL), and other minor copigments were identified in the ethanol extract of Hibiscus rosa sinensis. The extracts can be coelectrospun with polycaprolactone and polyethylene oxide into fiber mats and were sensitive to pH changes from 1 to 13 with a unique color code (ΔE > 5). The pH sensor was used to monitor shrimp quality under isothermal conditions to obtain the respective activation energy (Ea in kJ/mol) of the sensors' color-change response (20.2), measured pH (20.6), and trimethylamine nitrogen (24.6), indole (27.1), and total microbial counts (30.8). Together with the Pearson correlation coefficient, the results showed high correlations between the sensors' color change and other quality parameters (p < 0.001). The regression equation developed by conducting the kinetic analysis was also suitable for predicting shrimp quality at refrigeration temperatures (4-10 °C) and can be used as a marker to monitor shrimp quality by visually inspecting the item condition.
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Hibiscus , Nanopartículas Metálicas , Rosa , Colorimetria , Concentração de Íons de Hidrogênio , Cinética , Extratos Vegetais , PrataRESUMO
Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 µM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 µM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.
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Adipogenia/efeitos dos fármacos , Diarileptanoides/química , Diarileptanoides/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/fisiologia , Adipocinas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcuma/química , Curcumina/análise , Curcumina/farmacologia , Enzimas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , PPAR gama/química , PPAR gama/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.
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Embucrilato/química , Mandíbula/crescimento & desenvolvimento , Nanopartículas/química , Osteogênese , Tiofenos/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Mandíbula/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/ultraestrutura , Imagem Óptica , Osteocalcina/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Eletricidade EstáticaRESUMO
Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel. Concentrations of HA and o-/m-/p-MHAs were normalized to those of creatinine and used to analyze urine samples of 160 operating room (OR) healthcare personnel, including administrative staff, surgical nurses, nurse anesthetists, and surgeons. The results showed that the five analytes could be accurately separated and exhibited good linearity (r > 0.9992). The rate of recovery was between 86% and 106%, and the relative standard deviation was less than 5%. Urine from administrative staff presented the highest median concentration of hippuric acid (0.25 g/g creatinine); this was significantly higher than that found in the urine of surgeons (0.15 g/g). The concentrations of urinary o-/m-/p-MHAs in surgical nurses were higher than those in administrative staff, nurse anesthetists, and surgeons. Furthermore, the type, sex, and age of healthcare personnel were associated with changes in urine HA and o-/m-/p-MHA concentrations. Healthcare personnel should be aware of the risk of exposure to surgical smoke.
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Poluentes Ocupacionais do Ar/urina , Hipuratos/urina , Exposição Ocupacional/estatística & dados numéricos , Salas Cirúrgicas , Recursos Humanos em Hospital , Fumaça , Adulto , Poluentes Ocupacionais do Ar/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Creatinina , Atenção à Saúde , Humanos , Exposição Ocupacional/análise , Espectrometria de Massas em Tandem , Tolueno/metabolismo , Xilenos/metabolismoRESUMO
OBJECTIVES: The composition and concentration distribution of volatile organic compounds (VOCs) in surgical smoke had seldomly been reported. This study aimed to investigate the profile of VOCs and their concentration in surgical smoke from breast surgery during electrocautery in different tissues, electrosurgical units, and electrocautery powers. METHODS: Thirty-eight surgical smoke samples from 23 patients performed breast surgery were collected using evacuated stainless steel canisters. The concentrations of 87 VOCs in surgical smoke samples were analyzed by gas chromatography-mass spectrometry. The human tissues, electrosurgical units, and electrocautery power were recorded. RESULTS: The median level of total VOCs concentrations in surgical smoke samples from mammary glands (total VOCs: 9953.5 ppb; benzene: 222.7 ppb; 1,3-butadiene: 856.2 ppb; vinyl chloride: 3.1 ppb) using conventional electrosurgical knives were significantly higher than that from other tissues (total VOCs: 365.7-4266.8 ppb, P < 0.05; benzene: 26.4-112 ppb, P < 0.05; 1,3-butadiene: 15.6-384 ppb, P < 0.05; vinyl chloride: 0.6-1.8 ppb, P < 0.05) using different electrosurgical units. A high methanol concentration was found in surgical smoke generated during breast surgery (641.4-4452.5 ppb) using different electrosurgical units. An electrocautery power of ≥ 27.5 watts used for skin tissues produced a higher VOCs concentration (2905.8 ppb). CONCLUSIONS: The surgical smoke samples collected from mammary glands using conventional electrosurgical knives had high VOCs concentrations. The carcinogens (including benzene, 1,3-butadiene, and vinyl chloride) and methanol were found in the surgical smoke samples from different electrosurgical units. The type of electrosurgical unit and electrocautery power used affected VOCs concentrations in surgical smoke.
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Poluentes Atmosféricos/análise , Salas Cirúrgicas , Compostos Orgânicos Voláteis/análise , Benzeno/análise , Neoplasias da Mama , Butadienos , Carcinógenos/análise , Eletrocoagulação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fumaça/análiseRESUMO
Salvia sclarea essential oil is used as an aromatic therapy for dysmenorrhea. Sclareol-one of the natural products isolated from S. sclarea-displays anti-inflammatory and antioxidant activities; however, researchers have not yet evaluated the mechanism related to the pain-relieving effect of sclareol. In the present study, we aimed to investigate the potential effect of sclareol in ex vivo and in vivo dysmenorrhea models, as well as its possible mechanism. In the ex vivo study of uterine tissue from Sprague Dawley (SD) rats, the uterine contraction amplitude was observed and recorded. In the in vivo study, we measured the uterine contraction pressure of SD rats and performed writhing tests on mice. The uterine tissues from the writhing test subjects were collected and analyzed by Western blot. The results demonstrated that sclareol inhibited prostaglandin (PG) F2α-, oxytocin-, acetylcholine-, carbachol-, KCl-, and Bay K 8644-induced uterine contraction and possessed an analgesic effect in the writhing test. Sclareol affects the Ca2+ level and regulates oxytocin receptor (OTR), myosin light chain kinase (MLCK), extracellular signal-regulated kinase, p-p38, cyclooxygenase-2 (COX-2), and phospho-myosin light chain 20 (p-MLC20) protein expression. Integrating these results, we suggest that sclareol is a potential alternative supplement for dysmenorrhea.
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Siamenoside I is a rare mogroside in Siraitia grosvenorii Swingle and has become one of the target ingredients in natural sweetener production. However, the complex structure of siamenoside I has hindered its production in various ways. Here, a yeast cell that produces a specific ß-glucosidase for siamenoside I conversion from mogroside V was constructed, and the enzymes were coelectrospun with poly(vinyl alcohol) followed by phenylboronic acid cross-linking to provide potential usage in the batch production process of Siamenoside I. A central composite design (CCD)-response surface methodology (RSM) was used to find the optimum coelectrospinning parameters. The pH stability and sodium dodecyl sulfate tolerance increased for the entrapped enzymes, and positive correlations between the fiber diameter and enzymatic activity were confirmed. The batch process showed an average siamenoside I production rate of 118 ± 0.08 mg L-1 h-1 per gram of fiber. This is the first research article showing specific siamenoside I production on enzyme-loaded electrospun fibers.
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Brettanomyces/enzimologia , Edulcorantes/química , Triterpenos/química , beta-Glucosidase/química , Brettanomyces/genética , Cucurbitaceae/química , Estabilidade Enzimática , Enzimas Imobilizadas/química , Álcool de Polivinil/químicaRESUMO
Exposure to air pollution during pregnancy leads to adverse pregnancy outcomes. Few studies have evaluated the influences of air quality, including environmental tobacco smoke (ETS) and particulate matter (PM), on fetal development, which this study examined. This longitudinal correlation study used multiple linear regression data analysis of PM2.5/PM10, self-reported ETS exposure, urinary cotinine level, maternal characteristics, and birth parameters (gestational week, body weight, body length, head, and chest circumferences) with the effect of air quality on fetal growth. The study included 74 pregnant women (mean age 31.9 ± 4.2 years, body mass index 23.6 ± 3.8 kg/m2, average gestational duration 38.5 ± 0.8 weeks). ETS exposure decreased birth length by ≥1 cm, and potentially is an independent risk factor for fetal growth restriction, and pregnant women should avoid indoor and outdoor ETS. However, neither PM2.5/PM10 nor ETS was associated with low birth weight or small for gestational age. This study adds to the evidence base that ETS exposure of nonsmoking pregnant women affects the fetal birth length. Family members should refrain from smoking near expectant mothers, although smoking in the vicinity of their residential surroundings potentially exposes mothers and their fetuses to ETS. Public pollution and childbirth education classes should include details of indoor ETS.
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Poluição do Ar , Poluição por Fumaça de Tabaco , Adulto , Poluição do Ar/efeitos adversos , Feminino , Desenvolvimento Fetal , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Gravidez , Estudos Prospectivos , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
Mogrosides are the major triterpenoidal saponins found in swingle, the fruit of Siraitia grosvenorii, which have recently been widely used throughout the world as natural food sweeteners. Among this class of compounds, mogroside III E (MG III E) exhibits the most intense sweetness, and it was also found to effectively regulate blood glucose levels. However, the relative abundance of naturally occurring MG III E is low compared to other mogrosides. Therefore, the purpose of this study was to enrich MG III E through biotransformation of fruit extracts and to develop a reliable method for its purification. We used HPLC coupled with mass spectrometry and nuclear magnetic resonance spectroscopy for metabolite analysis and identified MG III E as a major metabolite of Ganoderma lucidum mycelium. This organism converts the most abundant mogroside, mogroside V, to MG III E via a deglycosylation reaction; high levels of ß-glucosidase activities were also detected. In addition, we established an efficient purification method for MG III E using HP-20 macroporous resin. Optimization of the method was accomplished by kinetic model fitting, dynamic adsorption studies, and desorption experiments. The purity of MG III E was increased from 11.71% to 54.19%, with a 70%-76% recovery rate, and the scaled-up purification process allowed us to harvest 17.38 g of MG III E with 55.14% purity and a 74.71% of recovery rate. Therefore, our low cost, time-saving, easy to scale-up procedure for isolating MG III E could be applicable in industrial processes.
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Cucurbitaceae/química , Glucosídeos/isolamento & purificação , Reishi/metabolismo , Saponinas/metabolismo , Triterpenos/isolamento & purificação , Biotransformação , Frutas/química , Glucosídeos/metabolismo , Micélio , Edulcorantes , Triterpenos/metabolismoRESUMO
BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata. OBJECTIVE: We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice. METHODS: The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin. RESULTS: DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 µg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin ß-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery. CONCLUSION: Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications.
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Antibacterianos/farmacologia , Antrodia/química , Dermatite Atópica/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Tolueno/análogos & derivados , Tolueno/farmacologia , Administração Cutânea , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Linhagem Celular , Quimiocinas/imunologia , Quimiocinas/metabolismo , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Proteínas Filagrinas , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Ácido Nalidíxico/farmacologia , Ácido Nalidíxico/uso terapêutico , Ovalbumina/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Suínos , Tolueno/isolamento & purificação , Tolueno/uso terapêutico , Resultado do Tratamento , Perda Insensível de Água/efeitos dos fármacosRESUMO
PURPOSE: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of alpha(v) beta(3) integrin (αvß3) in the murine ALTS1C1 glioma cell line. MATERIALS AND METHODS: We investigated the uptake, toxicity and radiosensitivity of GNP-PEG-cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7 macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor model was tested using the inductively coupled plasma mass spectrometry. RESULTS: Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose enhancement factors are 1.21-1.66 and 1.14-1.33, respectively, for all radiations. CONCLUSION: Ultrasmall GNP-PEG-cRGD can be considered as a radiosensitizer. For radiotherapy applications, the delivery method should be developed to increase the GNP uptake in the tumor and decrease the uptakes in undesirable organs.
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Ouro/química , Nanopartículas Metálicas/química , Oligopeptídeos/química , Radiossensibilizantes/química , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Endocitose , Glioma/patologia , Integrina alfaVbeta3/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Peptídeos/química , Fótons , Polietilenoglicóis/química , Prótons , Células RAW 264.7 , Tolerância a Radiação , RadiometriaRESUMO
Dendrobium Taiseed Tosnobile, a new Dendrobium species developed by crossbreeding Dendrobium tosaense and Dendrobium nobile, exhibits the characteristics of high mass production and high polysaccharide content. This study investigated the structural characterization and immunostimulating effects of a polysaccharide isolated from D. Taiseed Tosnobile (DTTPS). DTTPS was fractioned using a DEAE-650M column to obtain the major neutral polysaccharide (DTTPS-N). The structural characteristics of DTTPS-N were investigated through high-performance anion exchange chromatography, high-performance size exclusion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. In the immunostimulating experiment, BALB/c mice were administered DTTPS (100 and 300mg/kg) daily for 3 weeks. The results revealed that DTTPS-N comprised arabinose, galactose, glucose, mannose, and xylose at a ratio of 1:1.5:3.0:29.9:1.3. DTTPS-N comprised (1â3; 1â4)-Man as the backbone, and its average molecular weight was 281kDa. Pharmacological experiments demonstrated that DTTPS substantially increased the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction. This is the first study to demonstrate the structural characteristics and immunopharmacological effects of an active polysaccharide derived from D. Taiseed Tosnobile.
Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Dendrobium/química , Caules de Planta/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Imunidade Inata/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Baço/citologiaRESUMO
Changbai Mountain Ginseng (CMG, Panax ginseng C.A. Mey) is a traditional medicine commonly found in Northeast China and grows at elevations of 2000 m or higher in the Changbai Mountain Range. CMG, considered to be a "buried treasure medicine", is priced higher than other types of ginseng. However, few studies have demonstrated the effects of CMG supplementation on exercise performance, physical fatigue, and the biochemical profile. The major compound of CMG extract was characterized by electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Male ICR mice were divided into 3 groups, the vehicle, CMG-1X and CMG-5X groups (n = 8 per group), and respectively administered 0, 5, or 25 mg/kg/day of CMG extract orally for four weeks. HPLC-ESI-MS/MS results showed that the major compound in CMG extract is ginsenoside Ro. CMG extract significantly increased muscle weight and relative muscle weight (%). CMG extract supplementation dose-dependently increased grip strength (p < 0.0001) and endurance swimming time, decreased levels of serum lactate (p < 0.0001), ammonia (p < 0.0001), creatine kinase (CK, p = 0.0002), and blood urea nitrogen (p < 0.0001), and economized glucose levels (p < 0.0001) after acute exercise challenge. The glycogen in the gastrocnemius muscle was significantly increased with CMG extract treatment. Biochemical profile results showed that creatinine and triacylglycerol significantly decreased and total protein and glucose increased with CMG treatment. This is the first report that CMG extract supplementation increases muscle mass, improves exercise performance and energy utilization, and decreases fatigue-associated parameters in vivo. The major component of CMG extract is ginsenoside Ro, which could be a potential bioactive compound for use as an ergogenic aid ingredient by the food industry.
Assuntos
Suplementos Nutricionais , Atividade Motora/efeitos dos fármacos , Panax/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Glicemia/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Fadiga/tratamento farmacológico , Fadiga/metabolismo , Glicogênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Força Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Condicionamento Físico Animal , Compostos Fitoquímicos/química , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
Chili pepper is used as a food, seasoning and has been revered for its medicinal and health claims. It is very popular and is the most common spice worldwide. Capsaicin (CAP) is a major pungent and bioactive phytochemical in chili peppers. CAP has been shown to improve mitochondrial biogenesis and adenosine triphosphate (ATP) production. However, there is limited evidence around the effects of CAP on physical fatigue and exercise performance. The purpose of this study was to evaluate the potential beneficial effects of CAP on anti-fatigue and ergogenic functions following physiological challenge. Female Institute of Cancer Research (ICR) mice from four groups (n = 8 per group) were orally administered CAP for 4 weeks at 0, 205, 410, and 1025 mg/kg/day, which were respectively designated the vehicle, CAP-1X, CAP-2X, and CAP-5X groups. The anti-fatigue activity and exercise performance was evaluated using forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen) and creatine kinase (CK) after a 15-min swimming exercise. The grip strength and exhaustive swimming time of the CAP-5X group were significantly higher than other groups. CAP supplementation dose-dependently reduced serum lactate, ammonia, BUN and CK levels, and increased glucose concentration after the 15-min swimming test. In addition, CAP also increased hepatic glycogen content, an important energy source for exercise. The possible mechanism was relevant to energy homeostasis and the physiological modulations by CAP supplementation. Therefore, our results suggest that CAP supplementation may have a wide spectrum of bioactivities for promoting health, performance improvement and fatigue amelioration.
Assuntos
Capsaicina/administração & dosagem , Suplementos Nutricionais , Exercício Físico/fisiologia , Fadiga Muscular/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Fármacos do Sistema Sensorial/administração & dosagem , Amônia/sangue , Animais , Glicemia/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Capsaicina/farmacologia , Capsicum/química , Creatina Quinase/sangue , Feminino , Glicogênio/metabolismo , Humanos , Ácido Láctico/sangue , Fígado/metabolismo , Camundongos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Fármacos do Sistema Sensorial/farmacologia , Natação/fisiologiaRESUMO
Bacteria and fungi can secrete extracellular enzymes to convert macromolecules into smaller units. Hyperproduction of extracellular enzymes is often associated with alterations in cell wall structure in fungi. Recently, we identified that Saccharomyces cerevisiae kre6Δ mutants can efficiently convert mogroside V into mogroside III E, which has antidiabetic properties. However, the underlying efficient bioconversion mechanism is unclear. In the present study, the mogroside (MG) bioconversion properties of several cell wall structure defective mutants were analyzed. We also compared the cell walls of these mutants by transmission electron microscopy, a zymolyase sensitivity test, and a mannoprotein release assay. We found zymolyase-sensitive mutants (including kre1Δ, las21Δ, gas1Δ, and kre6Δ), with defects in mannoprotein deposition, exhibit efficient MG conversion and excessive leakage of Exg1; such defects were not observed in wild-type cells, or mutants with abnormal levels of glucans in the cell wall. Thus, yeast mutants defective in mannoprotein deposition may be employed to convert glycosylated bioactive compounds.