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1.
Biomed Chromatogr ; 38(4): e5828, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38321647

RESUMEN

The objective of this study is to explore the pharmacokinetics, tissue distribution, and excretion patterns of GL-V9 and its glucuronide metabolite, 5-O-glucuronide GL-V9, following the administration of GL-V9 to Sprague-Dawley (SD) rats. In this research, we developed and validated rapid, sensitive, and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for quantifying GL-V9 and 5-O-glucuronide GL-V9 in various biological samples, including SD rat plasma, tissue homogenate, bile, urine, and feces. Quantification of GL-V9 and 5-O-glucuronide GL-V9 in plasma, tissue homogenate, bile, urine, and feces was performed using the validated LC-MS/MS methods. The bioavailability of GL-V9 in SD rats ranged from 6.23% to 7.08%, and both GL-V9 and 5-O-glucuronide GL-V9 exhibited wide distribution and rapid elimination from tissues. The primary distribution tissues for GL-V9 and 5-O-glucuronide GL-V9 in rats were the duodenum, liver, and lung. GL-V9 was predominantly excreted in urine, while 5-O-glucuronide GL-V9 was primarily excreted in bile. GL-V9 exhibited easy absorption and rapid conversion to its glucuronide metabolite, 5-O-glucuronide GL-V9, following administration.


Asunto(s)
Glucurónidos , Espectrometría de Masas en Tándem , Ratas , Animales , Ratas Sprague-Dawley , Glucurónidos/química , Cromatografía Liquida/métodos , Distribución Tisular , Espectrometría de Masas en Tándem/métodos , Heces/química , Cromatografía Líquida de Alta Presión/métodos
2.
One Health Adv ; 1(1): 12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37521533

RESUMEN

Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We demonstrated that Bi-Nab exhibited higher binding affinity to the Delta spike protein than its parental antibodies and presented an extended inhibition breadth of preventing RBD binding to angiotensin-converting enzyme 2 (ACE2), the cellular receptor of SARS-CoV-2. In addition, pseudovirus neutralization results showed that Bi-Nab improved the neutralization potency and breadth with a lower half maximum inhibitory concentration (IC50) against wild-type SARS-CoV-2, variants being monitored (VBMs) and variants of concern (VOCs). Notably, the IgG-like Bi-Nab enhanced the neutralizing activity against Omicron variants with potent capabilities for transmission and immune evasion in comparison with its parental monoclonal antibody (mAb) 32C7 and a cocktail (with the lowest IC50 values of 31.6 ng/mL against the Omicron BA.1 and 399.2 ng/mL against the Omicron BA.2), showing evidence of synergistic neutralization potency of Bi-Nab against the Omicron variants. Thus, Bi-Nab represents a feasible and effective strategy against SARS-CoV-2 variants of concern.

3.
PLoS One ; 18(6): e0286467, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37285365

RESUMEN

GL-V9, a new synthetic flavonoid derived from wogonin, has shown beneficial biological functions. In this study, accurate and sensitive UPLC-MS/MS methods were developed and validated for the quantification of GL-V9 and its glucuronide metabolite (5-O-glucuronide GL-V9) in Beagle dog plasma. The chromatographic separation was performed on a C8 column (ACE Excel 5 C8 50×3.0 mm) using 0.1% formic acid and acetonitrile were used as mobile phase. Mass detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) interface operating in positive ion mode. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode with the transitions of m/z 410.2→126.1 for GL-V9, m/z 586.3→410.0 for 5-O-glucuronide GL-V9 and m/z 180.0→110.3 for phenacetin (internal standard), respectively. The calibration curves for GL-V9 and 5-O-glucuronide GL-V9 showed excellent linearity over the concentration range of 0.5-500 ng/mL with correlation coefficient greater than 0.99. The intra- and inter-day accuracies were within 99.86% to 109.20% for GL-V9 and 92.55% to 106.20% for 5-O-glucuronide GL-V9, respectively. The mean recovery was 88.64% ± 2.70% for GL-V9, and 92.31% ± 6.28% for 5-O-glucuronide GL-V9, respectively. The validated method was successfully applied to the pharmacokinetic study in Beagle dogs after oral and intravenous administration. The oral bioavailability of GL-V9 was approximately 2.47%~4.35% in Beagle dogs and reached steady state on the fifth day after repeated dosing.


Asunto(s)
Glucurónidos , Espectrometría de Masas en Tándem , Perros , Animales , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Cromatografía Líquida de Alta Presión/métodos , Flavonoides , Reproducibilidad de los Resultados
4.
PLoS One ; 18(2): e0280346, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36763685

RESUMEN

Compared with other point clouds, the airborne LiDAR point cloud has its own characteristics. The deep learning network PointNet++ ignores the inherent properties of airborne LiDAR point, and the classification precision is low. Therefore, we propose a framework based on the PointNet++ network. In this work, we proposed an interpolation method that uses adaptive elevation weight to make full use of the objects in the airborne LiDAR point, which exhibits discrepancies in elevation distributions. The class-balanced loss function is used for the uneven density distribution of point cloud data. Moreover, the relationship between a point and its neighbours is captured, densely connecting point pairs in multiscale regions and adding centroid features to learn contextual information. Experiments are conducted on the Vaihingen 3D semantic labelling benchmark dataset and GML(B) benchmark dataset. The experiments show that the proposed method, which has additional contextual information and makes full use of the airborne LiDAR point cloud properties to support classification, achieves high accuracy and can be widely used in airborne LiDAR point classification.


Asunto(s)
Benchmarking , Etiquetado de Productos , Semántica
5.
Food Funct ; 14(1): 215-230, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36477974

RESUMEN

Aging is an inevitable physiological process associated with an imbalance in the oxidative defense system. Angelica sinensis, a kind of traditional Chinese medicine (TCM), has anti-oxidant effects and has been considered as a potential supplement in anti-aging treatment. Nevertheless, it has the disadvantages of slow efficacy and long duration of treatment. Fermentation, as an efficient biotechnological approach, is beneficial for improving the nutritional capacity of the material. Fermented TCMs are considered to be more effective. In this study, fermented Angelica sinensis (FAS) and non-fermented Angelica sinensis (NFAS) were used to investigate changes in the chemical constituents. Furthermore, the improvement effect of FAS on D-galactose-induced aging in mice and the potential mechanisms were explored. The results revealed that FAS and NFAS had different constituents under the influence of fermentation, such as 3-phenyllactic acid, L-5-hydroxytryptophan, taxifolin and methyl gallate. These elevated constituents of FAS might help increase the ability of FAS to improve aging. The aging model was established by intraperitoneal injection of D-galactose (2.5 g kg-1 day-1) for 44 days, and FAS (3 g kg-1 day-1) was administered daily by oral gavage after 2 weeks of induction with D-galactose. FAS was observed to significantly ameliorate changes associated with liver aging, such as reduction of MDA, AGEs and 8-OHdG. The contents of pro-inflammatory cytokines containing TNF-α, IL-1ß and IL-6 were significantly suppressed in the FAS group. In addition, FAS activated Nrf2 signaling better than NFAS, improved the expression of Nrf2, HO-1, NQO1, GCLC, GCLM and GSS, and further increased the activities of SOD, CAT and other antioxidant enzymes in the liver. Simultaneously, it had a certain repair effect on the liver tissues of mice. The intestinal microbiota analysis showed that FAS could regulate the microbiota imbalance caused by aging, increase the ratio of Firmicutes/Bacteroidetes by 95% and improve the relative abundance of beneficial bacteria related to Nrf2 signaling, such as Lactobacillus. Besides, fecal metabolite analysis identified uric acid as an evidential metabolite, suggesting that FAS participates in purine metabolism to improve aging. Therefore, the regulation of intestinal microbiota and metabolism may be one of the important mechanisms of FAS in alleviating hepatic oxidative stress via the gut-liver axis. The results of this study could provide information for the future development of postbiotic products that may have beneficial effects on the prevention or treatment of aging.


Asunto(s)
Angelica sinensis , Microbioma Gastrointestinal , Ratones , Animales , Angelica sinensis/química , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Galactosa/metabolismo , Hígado/metabolismo , Envejecimiento , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/metabolismo
6.
Foods ; 11(22)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36429192

RESUMEN

Lactiplantibacillus plantarum LZU-J-TSL6 with high γ-aminobutyric acid (GABA) production (3.838 g/L) was screened and isolated from the Chinese fermented food snack "Jiangshui". The improvement effect on anxiety disorder was explored using mice as animal models. In vitro results revealed that LZU-J-TSL6 had the potential to colonize the intestine (p < 0.01) and the anxiety-like behavior of the mice after seven days' gavage with LZU-J-TSL6 was significantly improved (p < 0.01) when compared to the model group. LZU-J-TSL6 was able to effectively increase the GABA content in the mice hippocampus (p < 0.0001) and restore some markers related to anxiety such as brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and 5-hydroxytryptamine (5-HT). Simultaneously, it had a certain repair effect on Nissl bodies and colon tissue in mice hippocampus. In addition, LZU-J-TSL6 increased the relative abundance of beneficial bacteria Bacteroides and Muribaculum, thereby regulating the imbalance of intestinal microbiota caused by anxiety disorder. It also affects the nerve pathway and intestinal mucosal barrier by increasing the content of glutamine and γ-aminobutyric acid and other related metabolites, thereby improving anxiety. Therefore, the GABA-producing Lactobacillus plantus LZU-J-TSL6 can be used as a probiotic to exert an indirect or direct anti-anxiety effect by maintaining the balance of the intestinal environment, producing related metabolites that affect nerve pathways and repair the intestinal mucosal barrier. It can be used as an adjuvant treatment to improve anxiety disorders.

7.
Microb Pathog ; 171: 105739, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36055570

RESUMEN

Gut microbial dysbiosis during the development of Hepatitis C virus and liver-related diseases is not well studied. Nowadays, HCV and liver cirrhosis are the major concerns that cause gut bacterial alteration, which leads to dysbiosis. For this purpose, the present study was aimed at correlating the gut bacterial community of the control group in comparison to HCV and liver cirrhotic patients. A total of 23 stool samples were collected, including control (9), liver cirrhotic (8), and HCV (6). The collected samples were subjected to 16 S rRNA Illumina gene sequencing. In comparison with control, a significant gut bacterial alteration was observed in the progression of HCV and liver cirrhosis. Overall, Firmicutes were significantly abundant in the whole study. No significant difference was observed in the alpha diversity of the control and patient studies. Additionally, the beta diversity based on non-metric multidimensional scaling (NMDS) has a significant difference (p = 0.005) (ANOSIM R2 = 0.14) in all groups. The discriminative results based on the LEfSe tool revealed that the HCV-infected patients had higher Enterobacteriaceae and Enterobacterial, as well as Lactobacillus and Bacilli in comparison than the liver-cirrhotic patients. These taxa were significantly different from the control group (p < 0.05). Regarding prospects, a detailed analysis of the function through metagenomics and transcriptomics is needed.


Asunto(s)
Microbioma Gastrointestinal , Hepatitis C , Hepatopatías , Bacterias/genética , Disbiosis/microbiología , Enterobacteriaceae/genética , Hepacivirus/genética , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática , Proyectos Piloto , ARN Ribosómico 16S/genética
8.
Clin Exp Nephrol ; 26(6): 512-521, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35195816

RESUMEN

OBJECTIVE: To explore the effect of RORA on LPS-induced renal epithelial cell apoptosis and the underlying mechanism. METHODS: LPS-treated HK-2 cells were established as a cellular model of acute kidney injury. The expression of RORA or/and PGC-1α in LPS-induced HK-2 cells was altered by transfection. qRT-PCR and Western blotting were used to detect the expression changes of RORA and PGC-1α. ELISA was performed to detect the expression of IL-1ß and IL-6 and the activity of caspase-3. Western blotting was applied for visualization of cleaved caspase-3. CCK-8 and flow cytometry were used to assess cell proliferation and apoptosis. Dual-luciferase reporter and ChIP-qPCR were utilized to verify the binding of RORA to PGC-1α promoter. RESULTS: LPS treatment decreased the expression of RORA and PGC-1α and increased that of cleaved caspase-3 in HK-2 cells. Also, LPS treatment inhibited HK-2 cell proliferation and promoted HK-2 cell apoptosis and secretion of IL-1ß and IL-6. Overexpression of RORA or PGC-1α eliminated the adverse effects of LPS treatment in HK-2 cells. RORA drove the transcription of PGC-1α by binding PGC-1α promoter. Knockdown of PGC-1α offset the reduction in HK-2 cell injury caused by overexpression of RORA. CONCLUSION: RORA reduces LPS-induced apoptosis of renal epithelial cells by promoting PGC-1α transcription.


Asunto(s)
Interleucina-6 , Lipopolisacáridos , Apoptosis , Caspasa 3/metabolismo , Células Epiteliales/metabolismo , Humanos , Interleucina-6/genética , Lipopolisacáridos/farmacología , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/farmacología
10.
PLoS One ; 16(5): e0251281, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33956839

RESUMEN

Robotic total stations have been widely used in continuous automatic monitoring of dam deformations. In this regard, monitoring accuracy is an important factor affecting deformation analysis. First the displacements calculation methods for dam deformation monitoring with total stations are presented, and the corresponding mean square error formulas are derived. Then for errors caused by atmospheric refraction, two correction methods are described. Simulations were conducted to compare the displacement accuracy calculated through different methods. It indicated that the difference between polar coordinate method and forward intersection is less than 0.5mm within around 400m' monitoring range, and in such cases, the polar coordinate method is preferred, as only one total station is required. Refraction correction tests with observations from two dams demonstrated that both correction methods could effectively enhance the monitoring accuracy. For observation correction, correction through the closest reference point achieves better correction results.

11.
Environ Sci Technol ; 53(7): 3773-3781, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30865825

RESUMEN

The interactions between nanoparticles and humic acid (HA) are critical to understanding the environmental risks and applications of nanoparticles. However, the interactions between HA fractions and graphene oxide (GO, a popular carbon nanosheet) at the molecular level remain largely unclear. Four HA fractions with molecular weights ranging from 4.6 to 23.8 kDa were separated, and the large HA fractions presented low oxygen contents and many aromatic structures. The binding constants of the large HA fractions on GO were 2.6- to 3551-fold higher than those of the small HA fractions, while the maximum adsorption capacities of the larger HA fractions onto GO were much higher. Atomic force microscopy (AFM) found that the small and large HA fractions were spread over the center and the edge of the GO nanosheets, respectively. Density functional theory (DFT) simulation and nuclear magnetic resonance spectroscopy confirmed the above phenomena (three adsorption patterns, "vs", "ps", and "pea") and revealed that HA bonded to the GO nanosheets mainly through van der Waals force and π-π interactions. The integrating analysis of binding affinity, AFM, and DFT provides new insights into the environmental behavior of GO and the applications of GO in pollutant removal under exposure from HA.


Asunto(s)
Grafito , Adsorción , Teoría Funcional de la Densidad , Sustancias Húmicas , Interferometría , Microscopía de Fuerza Atómica , Óxidos
12.
Exp Ther Med ; 16(2): 1426-1432, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30116391

RESUMEN

The aim of the present study was to investigate the effect of propofol on immunoglobulin (Ig)E-activated mast cell degranulation and explore the underlying mechanisms responsible. RBL-2H3 cells were treated with propofol for at a variety of concentrations and different amounts of time. Cell viability was assessed using an MTT assay and microRNA (miR)-221 expression was quantified using reverse transcription-quantitative polymerase chain reaction. RBL-2H3 cells were transfected with miR-221 mimic or a negative control and degranulation, including the release of ß-hexosaminidase and histamine, was evaluated using an ELISA kit. The effect of miR-221 overexpression on the phosphorylation of protein kinase B (Akt) was detected using western blotting and extracellular Ca2+ influx was measured via afura-2 assay. The phosphoinositide 3-kinase(PI3K) inhibitor LY294002 was used to investigate the association between PI3K/Akt signaling and Ca2+ influx in the presence of propofol. The results demonstrated that propofol treatment suppressed RBL-2H3 cell proliferation in a dose- and time-dependent manner. Propofol inhibited miR-221 expression in a dose-dependent manner compared with the control group; however, the inhibitive effect was significantly abrogated following transfection with miR-221 mimics. Furthermore, ß-hexosaminidase and histamine release, PI3K/Akt signaling and Ca2+ influx were decreased following propofol application. miR-221 overexpression markedly ameliorated the suppressive effect of propofol. Treatment with LY294002 reversed the propofol-induced decrement of Ca2+ influx on IgE-mediated RBL-2H3 cells, suggesting an association between PI3K/Akt signaling and Ca2+ influx. In conclusion, the results of the present study suggest that propofol treatment attenuates mast cell degranulation via inhibiting the miR-221/PI3K/Akt/Ca2+ pathway. These results indicate that propofol may have a potential therapeutic effect as a treatment for allergic diseases.

13.
J Steroid Biochem Mol Biol ; 172: 69-78, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28583875

RESUMEN

Bile acid homeostasis is maintained by liver synthesis, bile duct secretion, microbial metabolism and intestinal reabsorption into the blood. When drug insults result in liver damage, the variances of bile acids (BAs) are related to the physiological status of the liver. Here, we established a method to simultaneously quantify 19 BAs in rat plasma, liver, bile and different intestinal section contents (duodenum, jejunum, ileum, cecum and colon) using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the pattern of bile acid homeostasis in the enterohepatic circulation of bile acids in physiological situations. Dynamic changes in bile acid composition appeared throughout the enterohepatic circulation of the BAs; taurine- and glycine-conjugated BAs and free BAs had different dynamic homeostasis levels in the circulatory system. cholic acid (CA), beta-muricholic acid (beta-MCA), lithocholic acid (LCA), glycocholic acid (GCA) and taurocholic acid (TCA) greatly fluctuated in the bile acid pool under physiological conditions. Taurine- and glycine-conjugated bile acids constituted more than 90% in the bile and liver, whereas GCA and TCA accounted for more than half of the total bile acids and the secretion of bile mainly via conjugating with taurine. While over 80% of BAs in plasma were unconjugated bile acids, CA and HDCA were the most abundant elements. Unconjugated bile acids constituted more than 90% in the intestine, and CA, beta-MCA and HDCA were the top three bile acids in the duodenum, jejunum and ileum content, but LCA and HDCA were highest in the cecum and colon content. As the main secondary bile acid converted by microflora in the intestine, LCA was enriched in the cecum and DCA mostly in the colon. As endogenous substances, the concentrations of plasma BAs were closely related to time rhythm and diet. In conclusion, analyzing detailed BA profiles in the enterohepatic circulation of bile acids in a single run is possible using LC-MS/MS. Based on the physiological characteristics of the metabolic profiling of 19 BAs in the total bile acid pool and the time rhythm variation of the endogenous bile acids, this study provided a new valuable method and theoretical basis for the clinical research of bile acid homeostasis.


Asunto(s)
Ácidos y Sales Biliares/sangre , Homeostasis/fisiología , Hígado/química , Metabolómica , Animales , Ácidos y Sales Biliares/química , Ácidos y Sales Biliares/clasificación , Ciego/química , Cromatografía Líquida de Alta Presión , Colon/química , Duodeno/química , Glicina/sangre , Glicina/química , Íleon/química , Yeyuno/química , Masculino , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Taurina/sangre , Taurina/química , Factores de Tiempo
14.
Bioanalysis ; 5(20): 2521-30, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24138625

RESUMEN

BACKGROUND: YF-49-92.MLS is a novel candidate for TB treatment. An accurate, precise and specific LC-MS/MS method for the quantification of YF-49-92.MLS in rat plasma using verapamil as an IS is reported in this paper. METHODOLOGY: Proper retention time and excellent peak shape were acquired using an Agilent Zorbax(®) SB-C18 column with the mobile phase of 5 mmol/l ammonium acetate, 0.1% formic acid-methanol (30:70, v/v). The LLOQ was 1 ng/ml. The calibration curves encompassed concentrations from 20 to 5000 ng/ml. Intra- and inter-assay precision and accuracy were within 15% by determining low, medium and high concentration samples. Extraction recovery, stability, and matrix effects were also fully validated. CONCLUSION: This method has been validated to be rapid and sensitive, and successfully applied to the PK study of YF-49-92.MLS in rat plasma.


Asunto(s)
Antituberculosos/sangre , Cromatografía Liquida/métodos , Imidazoles/sangre , Oxazinas/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Acetatos , Animales , Calibración , Cromatografía Liquida/normas , Femenino , Formiatos , Masculino , Metanol , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/normas , Espectrometría de Masas en Tándem/normas , Verapamilo/sangre
15.
Artículo en Chino | MEDLINE | ID: mdl-22403894

RESUMEN

OBJECTIVE: To investigate the feasibility of contralateral C7 nerve transfer via posterior spinal route for treatment of brachial plexus root avulsion injury by anatomical study. METHODS: Ten cadaveric specimens of 7 men and 3 women were selected, who had no obvious deformity and no tissue defect in neck neutral position. By simulating surgical exploration of brachial plexus injury, the length of contralateral C7 nerve root was elongated by dissecting its anterior and posterior divisions to the distal end, while the length of C7 nerve from the intervertebral foramen to the branching point and the length of the anterior and posterior divisions were measured. By simulating cervical posterior approach, the C7 vertebral plate and T1 spinous process were fully exposed; the hole was made near vertebral body; and the C7 nerve root lengths by posterior vertebra path to the contralateral upper trunk and lower trunk were measured. RESULTS: C7 nerve root length was (58.62 +/- 8.70) mm; the length of C7 nerve root plus posterior or anterior division was (65.15 +/- 9.11) mm and (70.03 +/- 10.79) mm, respectively. By posterior spinal route, the distance was (72.12 +/- 10.22) mm from the end of C7 nerve to the contralateral upper trunk of brachial plexus, and was (95.21 +/- 12.50) mm to the contralateral lower trunk of brachial plexus. CONCLUSION: Contralateral C7 nerve can be transferred to the contralateral side through posterior spinal route and it only needs short bridge nerve or no. The posterior spinal route can effectively prevent from neurovascular injury, so it might be the best surgery approach for the treatment of brachial plexus root avulsion injury.


Asunto(s)
Plexo Braquial/anatomía & histología , Plexo Braquial/lesiones , Transferencia de Nervios , Vértebras Cervicales/cirugía , Femenino , Humanos , Masculino , Raíces Nerviosas Espinales/anatomía & histología , Raíces Nerviosas Espinales/lesiones
16.
Nanoscale Res Lett ; 5(10): 1561-9, 2010 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-21076708

RESUMEN

The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs). The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride); however, the zeta potential of CoQ10-LNCs was above /- 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC) in one heating-cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM). The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds.

17.
Int J Pharm ; 392(1-2): 57-63, 2010 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-20302925

RESUMEN

Skin photo-ageing induced by ultraviolet (UV) radiation is mainly ascribed to oxidative stress and reactive oxygen species (ROS). Coenzyme Q10 (CoQ10) has been reported as a powerful antioxidant in plasma. However, CoQ10 was barely satisfactory in topical drug delivery because of its lipid solubility. To improve the anti-oxidative efficiency of CoQ10 in skin photo-ageing, the present research prepared a novel CoQ10 nano-structured lipid carrier (CoQ10-NLC) and characterised it by size and freeze-fracture transmission electron microscopy (FF-TEM). In UVA-irradiated fibroblasts, the protection of CoQ10-NLC was more effective than the CoQ10-emulsion as demonstrated by cell viability and morphological changes of the cell body and nucleus. In addition, malondialdehyde (MDA, the product of lipid peroxidation) concentration decreased by 61.5% in the group treated with CoQ10-NLC compared to the group subjected to general CoQ10-emulsion. In the presence of CoQ10-NLC, the activities of the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reinstated to 81% and 75%, respectively, of the control group. In vivo, the CoQ10-NLC displayed a stronger capability to penetrate the stratum corneum and permeate the dermis after a topical skin application. These results reveal that CoQ10-NLC has greater antioxidant properties and topical skin penetration than the CoQ10-emulsion.


Asunto(s)
Portadores de Fármacos/química , Lípidos/química , Nanoestructuras/química , Envejecimiento de la Piel , Protectores Solares/administración & dosificación , Ubiquinona/análogos & derivados , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Células Cultivadas , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de la radiación , Glutatión Peroxidasa/metabolismo , Humanos , Peróxidos Lipídicos/metabolismo , Microscopía Electrónica de Transmisión , Modelos Biológicos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/enzimología , Piel/metabolismo , Piel/efectos de la radiación , Absorción Cutánea/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Solubilidad , Protectores Solares/química , Protectores Solares/farmacocinética , Superóxido Dismutasa/metabolismo , Propiedades de Superficie , Ubiquinona/administración & dosificación , Ubiquinona/química , Ubiquinona/farmacocinética , Rayos Ultravioleta/efectos adversos
18.
BMB Rep ; 42(10): 648-54, 2009 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-19874709

RESUMEN

Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) genes has been reported to play an important role in protecting host cells from oxidative injury in several model systems. A radish phospholipid hydroperoxide glutathione peroxidase (RsPHGPx) known to have high catalytic activity was applied to mouse 3T3 fibroblasts to determine the protective effects of PHGPx against oxidative injury triggered by hydroperoxides such as hydrogen peroxide (H(2)O(2)), tert-butyl hydroperoxide (t-BHP) and phosphatidylcholine hydroperoxide (PCOOH). We observed that preincubation of cells with RsPHGPx significantly increased cell viability, reduced levels of malondialdehyde (MDA), inhibited generation of reactive oxygen species (ROS), and maintained natural cell shapes after treatment with H(2)O(2), t-BHP or PCOOH, indicating that the exogenous RsPHGPx can act as an effective hydroperoxide-scavenger and may also protect target cells from oxidative damage. These results suggest the possibility for use of RsPHGPx as a therapeutic protectant.


Asunto(s)
Citoprotección/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Glutatión Peroxidasa/farmacología , Peróxido de Hidrógeno/toxicidad , Raphanus/enzimología , Células 3T3 , Animales , Supervivencia Celular/efectos de los fármacos , Fibroblastos/metabolismo , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Ratones , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/farmacología
19.
J Huazhong Univ Sci Technolog Med Sci ; 29(4): 409-12, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19662352

RESUMEN

This study investigated the ability of millimeter-wave (MMW) to promote the differentiation of bone marrow stromal cells (BMSCs) into cells with a neural phenotype. The BMSCs were primarily cultured. At passage 3, the cells were induced by beta-mercaptoethanol (BME) in combination with MMW or BME alone. The expressions of nucleostemin (NS) and neuron-specific enolase (NSE) were detected by immunofluorescent staining and Western blotting respectively to identify the differentiation. The untreated BMSCs predominately expressed NS. After induced by BME and MMW, the BMSCs exhibited a dramatic decrease in NS expression and increase in NSE expression. The differentiation rate of the cells treated with BME and MMW in combination was significantly higher than that of the cells treated with BME alone (P<0.05). It was concluded that MMW exposure enhanced the inducing effect of BME on the differentiation of BMSCs into cells with a neural phenotype.


Asunto(s)
Células de la Médula Ósea/efectos de la radiación , Diferenciación Celular/efectos de la radiación , Microondas , Neuronas/citología , Células del Estroma/efectos de la radiación , Animales , Células de la Médula Ósea/citología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Mercaptoetanol/farmacología , Fenotipo , Ratas , Células del Estroma/citología
20.
Nanoscale Res Lett ; 5(1): 224-30, 2009 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-20652152

RESUMEN

Purpose of this study was to establish a lecithin nanoemulsion (LNE) without any synthetic surfactant as a topical delivery vehicle and to evaluate its topical delivery potential by the following factors: particle size, morphology, viscosity, stability, skin hydration and skin penetration. Experimental results demonstrated that an increasing concentration of soybean lecithin and glycerol resulted in a smaller size LNE droplet and increasing viscosity, respectively. The droplet size of optimized LNE, with the glycerol concentration above 75% (w/w), changed from 92 (F10) to 58 nm (F14). Additionally, LNE, incorporated into o/w cream, improved the skin hydration capacity of the cream significantly with about 2.5-fold increase when the concentration of LNE reached 10%. LNE was also demonstrated to improve the penetrability of Nile red (NR) dye into the dermis layer, when an o/w cream, incorporated with NR-loaded LNE, applied on the abdominal skin of rat in vivo. Specifically, the arbitrary unit (ABU) of fluorescence in the dermis layer that had received the cream with a NR-loaded LNE was about 9.9-fold higher than the cream with a NR-loaded general emulsion (GE). These observations suggest that LNE could be used as a promising topical delivery vehicle for lipophilic compounds.

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