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1.
Front Pharmacol ; 15: 1348019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389919

RESUMEN

Depression is a prevalent mental disorder. However, clinical treatment options primarily based on chemical drugs have demonstrated varying degrees of adverse reactions and drug resistance, including somnolence, nausea, and cognitive impairment. Therefore, the development of novel antidepressant medications that effectively reduce suffering and side effects has become a prominent area of research. Polysaccharides are bioactive compounds extracted from natural plants that possess diverse pharmacological activities and medicinal values. It has been discovered that polysaccharides can effectively mitigate depression symptoms. This paper provides an overview of the pharmacological action and mechanisms, intervention approaches, and experimental models regarding the antidepressant effects of polysaccharides derived from various natural sources. Additionally, we summarize the roles and potential mechanisms through which these polysaccharides prevent depression by regulating neurotransmitters, HPA axis, neurotrophic factors, neuroinflammation, oxidative stress, tryptophan metabolism, and gut microbiota. Natural plant polysaccharides hold promise as adjunctive antidepressants for prevention, reduction, and treatment of depression by exerting their therapeutic effects through multiple pathways and targets. Therefore, this review aims to provide scientific evidence for developing polysaccharide resources as effective antidepressant drugs.

2.
ACS Appl Mater Interfaces ; 15(10): 13064-13072, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36854109

RESUMEN

Spatial hindrance of lithium polysulfide (LiPS) diffusion by inserting a barrier interlayer has been deemed as an effective strategy to restrict the shuttle effect in lithium-sulfur batteries (LSBs). However, the extra interlayer without reversible capacity production inevitably reduces the actual energy density of the battery. Herein, a freestanding α-MoO3 nanobelt interlayer with the decoration of TiN nanoparticles and carbon nanotubes (denoted as MCT) is established. To investigate the capacity compensation effect of the MCT during cell operations, X-ray absorption near-edge spectrometry is conducted. It is revealed that MoO3 can sustain a reversible Li intercalation/deintercalation in a voltage range of 1.8-2.8 V, providing 180 mAh g-1 of extra capacity for compensating sulfur cathode. In addition, the adsorption of the lithiated α-MoO3 toward LiPSs is further evaluated. By matching a high-loading sulfur cathode (3.0 mg cm-2), a superior capacity of 713.3 mAh g-1 can be retained after 100 cycles under the MCT assistance.

3.
Int J Biol Sci ; 19(2): 593-609, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36632449

RESUMEN

Septic acute kidney injury (AKI) is characterized by inflammation. Pyroptosis often occurs during AKI and is associated with the development of septic AKI. This study found that induction of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to a higher level can induce pyroptosis in renal tubular cells. Meanwhile, macrophage migration inhibitory factor (MIF), a subunit of NLRP3 inflammasomes, was essential for IGF2BP1-induced pyroptosis. A putative m6A recognition site was identified at the 3'-UTR region of E2F transcription factor 1 (E2F1) mRNA via bioinformatics analyses and validated using mutation and luciferase experiments. Further actinomycin D (Act D) chase experiments showed that IGF2BP1 stabilized E2F1 mRNA dependent on m6A. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) indicated that E2F1 acted as a transcription factor to promote MIF expression. Thus, IGF2BP1 upregulated MIF through directly upregulating E2F1 expression via m6A modification. Experiments on mice with cecum ligation puncture (CLP) surgery verified the relationships between IGF2BP1, E2F1, and MIF and demonstrated the significance of IGF2BP1 in MIF-associated pyroptosis in vivo. In conclusion, IGF2BP1 was a potent pyroptosis inducer in septic AKI through targeting the MIF component of NLRP3 inflammasomes. Inhibiting IGF2BP1 could be an alternate pyroptosis-based treatment for septic AKI.


Asunto(s)
Lesión Renal Aguda , Factores Inhibidores de la Migración de Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Lesión Renal Aguda/metabolismo , Inflamasomas , Inflamación , Riñón/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Mensajero
4.
Med Sci Monit ; 26: e921233, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32032347

RESUMEN

BACKGROUND Osteosarcoma is a common malignant tumor of musculoskeletal stromal cells. Osteosarcoma clinical behavior depends mostly on the histologic grade, the site of primary tumor, the response to chemotherapy, and the presence of pulmonary metastases. The aim of this study was to knockout SHOX CNE9/10 in U2OS osteosarcoma cells and to analyze the effects on cell growth and apoptosis. MATERIAL AND METHODS U2OS cells with CNE9 knockout and U2OS cells with CNE10 knockout were established via the CRISPR/Cas9 system. Sanger sequencing was used to detect the success of the knockdown experiment. Western blotting and quantitative polymerase chain reaction were used to detect the expression levels of short stature homeobox-containing gene (SHOX) protein and messenger RNA (mRNA) after knockdown of CNE9 and CNE10. The cell viability and apoptotic rate were detected by the Cell Counting Kit-8 method and by flow cytometry. RESULTS The Sanger sequencing results showed that the knockdown experiment was successful. The levels of SHOX mRNA and protein were significantly reduced after knocking down CNE9 and CNE10. Knockdown of CNE9 and CNE10 significantly increased the growth and inhibited the apoptosis of U2OS osteosarcoma cells. CNE9/CNE10 knockdown U2OS cells were successfully constructed. CONCLUSIONS Knockdown of CNE9 and CNE10 promoted U2OS cell growth and inhibited apoptosis by decreasing SHOX expression. This CNE9/CNE10 knockout U2OS cell model could provide a bridge for the research on SHOX and CNEs in osteosarcoma.


Asunto(s)
Apoptosis , Neoplasias Óseas/genética , ADN Intergénico/genética , Osteosarcoma/genética , Proteína de la Caja Homeótica de Baja Estatura/genética , Apoptosis/genética , Secuencia de Bases , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Técnicas de Inactivación de Genes , Humanos , Osteosarcoma/patología , Proteína de la Caja Homeótica de Baja Estatura/metabolismo
5.
J Food Sci ; 83(5): 1215-1220, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29660845

RESUMEN

In this study, gellan gums with different acyl contents were prepared, and their effects on blueberry cloudy juices were compared. The rheological properties, stability coefficients, sedimentations, color parameters and particle size distributions of blueberry cloudy juices with 0.035% (w/w) of gellan gum were measured. As the acyl content increased, the viscosity increased, and the sedimentation and stability coefficient values decreased. Gellan gums with higher acyl contents provided better beverage stabilizing capabilities through stricter enforcement of the molecular associations. Overall, this study provides valuable information for enhancing the gelation and stabilization of blueberry cloudy juices, confirms the superiority of high acyl gellan gums for inhibiting the color fading of anthocyanins, and further guides the development of novel product concepts. PRACTICAL APPLICATION: Cloudy juices made from blueberries have many benefits. However, the particles in cloudy juices will flocculate during storage, resulting in an undesirable precipitate. In our work, gellan gums with different acyl contents were prepared and applied to blueberry juice to prevent aggregation. The results provide valuable information for enhancing the stabilization of blueberry juices, confirm the superiority of high acyl gellan for inhibiting color fading, and further guide the development of novel product concepts.


Asunto(s)
Arándanos Azules (Planta) , Jugos de Frutas y Vegetales/análisis , Polisacáridos Bacterianos/química , Reología , Antocianinas/análisis , Color , Aditivos Alimentarios/análisis , Frutas , Geles/química , Modelos Teóricos , Tamaño de la Partícula , Gusto
6.
Insect Sci ; 25(6): 946-958, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28569426

RESUMEN

The diamondback moth, Plutella xylostella (L.), uses sulfatases (SULF) to counteract the glucosinolate-myrosinase defensive system that cruciferous plants have evolved to deter insect feeding. Sulfatase activity is regulated by post-translational modification of a cysteine residue by sulfatase modifying factor 1 (SUMF1). We identified 12 SULF genes (PxylSulfs) and two SUMF1 genes (PxylSumf1s) in the P. xylostella genome. Phylogenetic analysis of SULFs and SUMFs from P. xylostella, Bombyx mori, Manduca sexta, Heliconius melpomene, Danaus plexippus, Drosophila melanogaster, Tetranychus urticae and Homo sapiens showed that the SULFs were clustered into five groups, and the SUMFs could be divided into two groups. Profiling of the expression of PxylSulfs and PxylSumfs by RNA-seq and by quantitative real-time polymerase chain reaction showed that two glucosinolate sulfatase genes (GSS), PxylSulf2 and PxylSulf3, were primarily expressed in the midgut of 3rd- and 4th-instar larvae. Moreover, expression of sulfatases PxylSulf2, PxylSulf3 and PxylSulf4 were correlated with expression of the sulfatases modifying factor PxylSumf1a. The findings from this study provide new insights into the structure and expression of SUMF1 and PxylSulf genes that are considered to be key factors for the evolutionary success of P. xylostella as a specialist herbivore of cruciferous plants.


Asunto(s)
Regulación Enzimológica de la Expresión Génica , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/enzimología , Sulfatasas/química , Sulfatasas/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia Conservada , Proteínas de Insectos/genética , Mariposas Nocturnas/metabolismo , Especificidad de Órganos , Filogenia , Dominios Proteicos , Sulfatasas/genética
7.
J Affect Disord ; 195: 75-81, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26874244

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a serious debilitating psychiatric disorder. However, the molecular mechanisms of MDD remain largely unknown, and no objective laboratory-based tests are available to diagnose this disorder. METHODS: A gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was used to compare peripheral blood mononuclear cells (PBMC) metabolic profiling of 50 first onset drug-naïve MDD subjects and 50 healthy controls (training samples), to identify potential metabolite biomarkers for MDD. An independent sample cohort including 58 MDD patients, 40 schizophrenia (SCZ) patients and 56 healthy controls (test samples) was used to validate diagnostic generalizability and specificity of identified biomarkers. RESULTS: 17 PBMC metabolites responsible for discriminating MDD group from healthy control group were identified. These metabolites were mainly involved in disturbances of energy and neurotransmitter metabolism. This PBMC metabolite signature could effectively discriminate MDD subjects from the healthy controls with an AUC of 0.926 in training samples and 0.870 in test samples. Moreover, this metabolite signature enabled distinguishing MDD subjects from schizophrenia subjects with an AUC of 0.899. LIMITATIONS: This study was limited by potential confounding effects of different drug treatments in some MDD and schizophrenia subjects, and lack of animal studies to further validate the identified metabolite pathways in MDD. CONCLUSION: These findings suggest that early disturbances of PBMC energy and neurotransmitter metabolism may be associated with the onset of MDD. This PBMC metabolite signature may facilitate development of a laboratory-based diagnostic test for MDD.


Asunto(s)
Biomarcadores/sangre , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/diagnóstico , Metabolómica/métodos , Adulto , Animales , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Neurotransmisores/metabolismo , Esquizofrenia/sangre , Esquizofrenia/diagnóstico , Sensibilidad y Especificidad , alfa-Tocoferol/metabolismo
8.
J Transl Med ; 13: 226, 2015 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-26169624

RESUMEN

BACKGROUND: Schizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia. METHODS: Gas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group). RESULTS: The majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects. CONCLUSION: These findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder.


Asunto(s)
Glucosa/metabolismo , Leucocitos Mononucleares/metabolismo , Metabolómica/métodos , Esquizofrenia/metabolismo , Adulto , Biomarcadores/metabolismo , Estudios de Casos y Controles , Demografía , Trastorno Depresivo Mayor/metabolismo , Femenino , Humanos , Masculino , Metaboloma
9.
Sci Rep ; 4: 5855, 2014 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-25068480

RESUMEN

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.


Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Bipolar/orina , Metaboloma , Metabolómica/estadística & datos numéricos , Adulto , Área Bajo la Curva , Biomarcadores/orina , Trastorno Bipolar/fisiopatología , Estudios de Casos y Controles , Análisis Discriminante , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Imagen por Resonancia Magnética , Masculino , Metabolómica/métodos , Curva ROC
10.
Artículo en Inglés | MEDLINE | ID: mdl-24657409

RESUMEN

A high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS/MS) method was developed and validated to determine sitafloxacin in human plasma with dextrorphan as internal standard. Chromatographic separation was performed on a ZORBAX SB-C18 column (3.5µm, 2.1mm×100mm) with the mobile phase of methanol/water (containing 0.1% formic acid) (46:54, v/v) at a flow rate of 0.2mL/min. Quantification was performed using multiple-reaction monitoring of the transitions at m/z 410.2 → 392.2 for sitafloxacin and m/z 258.1 → 157.1 for dextrorphan, respectively. The calibration curve was linear over the range of 5-2500ng/mL with the lower limit of quantification of 5ng/mL for sitafloxacin. The intra- and inter-day precisions were less than 8.3% and the deviations of assay accuracies were within ±4.1%. Sitafloxacin was sufficiently stable under all relevant analytical conditions. This method was successfully applied to the pharmacokinetic study of sitafloxacin in healthy Chinese volunteers.


Asunto(s)
Cromatografía Liquida/métodos , Fluoroquinolonas/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Estabilidad de Medicamentos , Femenino , Fluoroquinolonas/química , Fluoroquinolonas/farmacocinética , Humanos , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados , Adulto Joven
11.
Mol Biosyst ; 10(4): 813-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24457555

RESUMEN

Bipolar disorder (BD) is a common and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. Here, we used a gas chromatography-mass spectrometry (GC-MS) based metabonomic method to characterize the urinary metabolic profiling of BD subjects and healthy controls to identify and validate urinary metabolite biomarkers for BD. Multivariate statistical analysis was used to visualize group discrimination and identify differentially expressed urinary metabolites in BD subjects relative to the healthy controls. Multivariate statistical analysis showed that the BD group was significantly distinguishable from the healthy control. Totally, 37 urinary metabolites responsible for discriminating BD subjects from healthy controls were identified. Interestingly, of 37 differential metabolites, 2,4-dihydroxypyrimidine was identified as an effective diagnostic biomarker for BD, yielding an area under the receiver operating characteristic curve (AUC) of 0.889 in the training samples (45 BD subjects and 61 healthy controls) and 0.805 in the test samples (26 BD subjects and 33 healthy controls). Our findings suggest that 2,4-dihydroxypyrimidine is a promising candidate urinary biomarker for BD, which may facilitate development of a urine-based diagnostic test for BD.


Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Bipolar/orina , Pirimidinas/orina , Adulto , Biomarcadores/orina , Índice de Masa Corporal , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metaboloma , Metabolómica , Curva ROC
12.
Biomed Chromatogr ; 28(3): 446-52, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24254834

RESUMEN

A sensitive and accurate HPLC-MS/MS method was developed for the simultaneous determination of dextromethorphan, dextrorphan and chlorphenamine in human plasma. Three analytes were extracted from plasma by liquid-liquid extraction using ethyl acetate and separated on a Kromasil 60-5CN column (3 µm, 2.1 × 150 mm) with mobile phase of acetonitrile-water (containing 0.1% formic acid; 50:50, v/v) at a flow rate of 0.2 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The calibration curve was linear over the range of 0.01-5 ng/mL for dextromethorphan, 0.02-5 ng/mL for dextrorphan and 0.025-20 ng/mL for chlorphenamine. The lower limits of quantification for dextromethorphan, dextrorphan and chlorphenamine were 0.01, 0.02 and 0.025 ng/mL, respectively. The intra- and inter-day precisions were within 11% and accuracies were in the range of 92.9-102.5%. All analytes were proved to be stable during sample storage, preparation and analytic procedures. This method was first applied to the pharmacokinetic study in healthy Chinese volunteers after a single oral dose of the formulation containing dextromethorphan hydrobromide (18 mg) and chlorpheniramine malaeate (8 mg).


Asunto(s)
Clorfeniramina/sangre , Cromatografía Líquida de Alta Presión/métodos , Dextrometorfano/sangre , Dextrorfano/sangre , Espectrometría de Masas en Tándem/métodos , Adulto , Clorfeniramina/química , Clorfeniramina/farmacocinética , Dextrometorfano/química , Dextrometorfano/farmacocinética , Dextrorfano/química , Dextrorfano/farmacocinética , Estabilidad de Medicamentos , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodos , Adulto Joven
13.
J Pharm Biomed Anal ; 88: 22-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24018419

RESUMEN

A pressure-assisted capillary zone electrophoresis method was developed to determine the pKa values of a triptolide derivative (LLDT-246) and its impurities. The method was performed in an uncoated fused-silica capillary under the electric voltage of 18kV and 50mbar of external pressure applied simultaneously. A series of running electrolyte buffers were used with pH ranging between 2.2 and 10.0 with the constant ionic strength of 0.05M. The values of pKa of LLDT-246 and two impurities were calculated based on the pH dependence of effective mobilities (µeff). The pKa value of LLDT-246 was in good agreement with that of determined by potentiometric titration method.


Asunto(s)
Diterpenos/química , Electroforesis Capilar/métodos , Fenantrenos/química , Automatización , Tampones (Química) , Química Farmacéutica , Diterpenos/análisis , Diseño de Fármacos , Electroquímica , Electrólitos , Compuestos Epoxi/análisis , Compuestos Epoxi/química , Concentración de Iones de Hidrógeno , Inmunosupresores/análisis , Iones , Modelos Químicos , Concentración Osmolar , Fenantrenos/análisis , Extractos Vegetales/análisis , Presión , Tripterygium/metabolismo
14.
J Zhejiang Univ Sci B ; 14(11): 1004-12, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24190446

RESUMEN

A relationship between status epilepticus (SE) and oxidative stress has recently begun to be recognized. To explore whether the flavonoids extracted from licorice (LFs) have any protective effect on kainate (KA)-induced seizure in mice, we treated mice with LFs before and after KA injection. In KA-treated mice, we found that superoxide dismutase (SOD) activity decreased immediately after the onset of seizure at 1 h and then increased at 6 h. It returned to baseline 1 d after seizure and then increased again at 3, 7, and 28 d, while malondialdehyde (MDA) content remained at a high level at 1 h, 6 h, 3 d, 7 d, and 28 d, indicating a more oxidized status related to the presence of more reactive oxygen species (ROS). Treatment with LFs before KA injection reversed the seizure-induced change in SOD activity and MDA content at 1 h, 6 h, 3 d, 7 d, and 28 d. Treatment with LFs after seizure decreased KA-induced SOD activity and MDA content at 7 and 28 d. Also, LF pre- and post-KA treatments decreased seizure-induced neuronal cell death. Subsequently, Morris water maze tests revealed that the escape latency was significantly decreased and the number of target quadrant crossings was markedly increased in the LF-treated groups. Thus, our data indicate that LFs have protective effects on seizure-induced neuronal cell death and cognitive impairment through their anti-oxidative effects.


Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Glycyrrhiza/química , Ácido Kaínico/toxicidad , Fármacos Neuroprotectores/farmacología , Estado Epiléptico/prevención & control , Animales , Trastornos del Conocimiento/prevención & control , Masculino , Malondialdehído/análisis , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo , Estado Epiléptico/inducido químicamente , Superóxido Dismutasa/metabolismo
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