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1.
Curr Drug Deliv ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39230001

RESUMEN

BACKGROUND: Combining Doxorubicin (DOX) with sorafenib (SF) is a promising strategy for treating Hepatocellular Carcinoma (HCC). However, strict dosage control is required for both drugs, and there is a lack of target selectivity. OBJECTIVE: This study aims to develop a novel nano-drug delivery system for the combined use of DOX and SF, aiming to reduce their respective dosages, enhance therapeutic efficacy, and improve target selectivity. METHODS: DOX/SF co-loaded liposomes (LPs) were prepared using the thin-film hydration method. The liposomes were modified with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)- polyethylene glycol (PEG2000), DSPE-PEG1000-cell penetrating peptide TAT, and Glycyrrhetinic Acid (GA). The basic properties of the liposomes were characterized. CCK-8 cell viability assays were conducted using HepG2, MHCC97-H, and PLC cell models, and apoptosis experiments were performed using HepG2 cells to determine if this delivery system could reduce the respective dosages of DOX and SF and enhance HCC cytotoxicity. Liposome uptake experiments were performed using HepG2 cells to validate the target selectivity of this delivery system. RESULTS: A GA/TAT-DOX/SF-LP liposomal nano drug delivery system was successfully constructed, with a particle size of 150 nm, a zeta potential of -7.9 mV, a DOX encapsulation efficiency of 92%, and an SF encapsulation efficiency of 88.7%. Cellular experiments demonstrated that this delivery system reduced the required dosages of DOX and SF, exhibited stronger cytotoxicity against liver cancer cells, and showed better target selectivity. CONCLUSION: A simple and referenceable liposomal nano drug delivery system has been developed for the combined application of DOX and SF in hepatocellular carcinoma treatment.

2.
Curr Pharm Des ; 29(2): 95-115, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36529920

RESUMEN

Currently, many therapeutic drugs are difficult to cross the blood-brain barrier (BBB), making it difficult to reach the site of action and thus fail to achieve the desired efficacy. In recent years, researchers and drug designers have increasingly focused on nanotechnology to break through the difficulty of small molecule inhibitors to cross the blood-brain barrier (BBB) and improve the success rate of drug delivery to the central nervous system. Among the common central neurological diseases, such as encephalitis, Parkinson's, Alzheimer's disease, and epilepsy, Alzheimer's disease has attracted much attention from researchers. Alzheimer's disease is a specific neurodegenerative disease, which causes irreversible degeneration of neurons as well as synapses in the brain, resulting in memory and cognitive dysfunction, along with other psychiatric symptoms and behavioral disorders, which seriously affects people's everyday life. Moreover, nanotechnology has excellent potential for application in AD treatment. Studies have shown that nanocarriers can target the delivery of chemotherapeutic drugs, antioxidants, and other therapeutic substances to brain tissue using existing physiological mechanisms, thus effectively alleviating the disease progression of AD. Therefore, various nanoparticles and nanomedicine have been developed and constructed for diagnosing and treating AD in the past decades, such as nanoparticles, bionanoparticles, liposomes, nano-gel, dendrimers, and self-assembled nanoparticles. This study aims to review the applications and results of nanotechnology in the treatment of Alzheimer's disease in recent years and provide some ideas and clues for future research and development of more effective drug delivery systems.


Asunto(s)
Enfermedad de Alzheimer , Nanopartículas , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Barrera Hematoencefálica , Encéfalo , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológico
3.
Pak J Pharm Sci ; 32(3 Special): 1333-1342, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31551212

RESUMEN

The MIC and MBC values of Shikuqin (SKQ) against 5 bacteria that readily cause diarrhea were measured by the broth micro dilution method. The castor oil-induced diarrhea method was used to evaluate the antidiarrheal activity. Intestinal transit and gastric emptying were also evaluated with normal and neostigmine-induced intestinal transit in rodents. In addition, the antidiarrheal activity of SKQ was assessed in vivo with isolated rabbit ileum. Xylene-induced ear edema was used to evaluate the anti-inflammatory activities in mice, while hot plate and writhing tests were performed to assess the analgesic effects. Senna decoction (0.3g/mL) was administered intragastrically to induce a rat model of diarrhea. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect AQP4 mRNA, and Western blot was performed to quantify the protein level of AQP4 in the colon. SKQ exhibits remarkable antidiarrheal, anti-inflammatory and analgesic effects in the gastrointestinal tract disorders, and can therefore be developed as a promising antidiarrheal agent.


Asunto(s)
Analgésicos/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antidiarreicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Animales , Acuaporina 4/genética , Acuaporina 4/metabolismo , Aceite de Ricino/efectos adversos , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Edema/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Polvos , Conejos , Ratas Sprague-Dawley
4.
Exp Ther Med ; 14(4): 3846-3850, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29042990

RESUMEN

The present study aimed to investigate changes of T-regulatory (Treg) and T-helper (Th)17 cells as well as cytokines in peripheral blood of children with acute bronchitis, and to explore the roles of these cells in the pathogenesis of acute bronchitis. A total of 126 children who had presented at Renji Hospital (Shanghai, China) with acute bronchitis were selected as the observation group and 30 healthy children were selected as the control group. Th17/Tregs in the peripheral blood of the children of the observation group and the control group was detected by flow cytometry. The levels of cytokines interleukin (IL)-17, IL-22, IL-10 and transforming growth factor (TGF)-ß in peripheral blood serum were detected by ELISA. Compared with those in the control group, Treg cells, the Treg/Th17 ratio as well as serum IL-10 and TGF-ß levels were significantly decreased in the observation group (P<0.05), while Th17 cells as well as serum levels of IL-17 and IL-22 were significantly increased (P<0.05). In conclusion, Treg/Th17 and the expression of associated cytokines lost their balance in children with acute bronchitis, suggesting that Treg and Th17 cells as well as their cytokines may be involved in the pathogenesis of acute bronchitis. It may be of certain guiding significance to detect Treg/Th17 and levels of serum cytokines in peripheral blood for clinical treatment.

5.
Rheumatol Int ; 37(3): 423-434, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27866247

RESUMEN

Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming children health. However, there is still lack of effective biomarkers for diagnosis JIA at early onset. We aim to construct a classification model to predict JIA disease. The peripheral blood gene expression profile data of JIA were downloaded from GEO database. We compared and analyzed differentially expressed genes (DEGs) between different JIA samples through Pearson's correlation coefficient method and unsupervised clustering analysis. Diagnostic model were constructed based on the deviation pathway through bioinformatics method. Eighteen specific correlated DEGs were obtained, but the correlations altered in different disease states. Although most JIA and control samples were clustered by unsupervised clustering analysis, respectively, a few JIA samples could not be clustered well. Four co-expression networks were next constructed with gene connections dynamically altered under variable conditions. Eight signaling pathways were significantly enriched including B/T cell receptor, ErbB and MAPK signaling pathways. The deviation scores of pathways were calculated. Applying these eight signaling pathways as feature to construct a classification model could predict JIA disease with high accuracies. Our data provide some light into pathogenic mechanism of JIA, the specific gene sets and the related signaling pathways may be potential biomarkers for diagnosis or therapeutic targets of JIA.


Asunto(s)
Artritis Juvenil/genética , Biología Computacional/métodos , Expresión Génica , Artritis Juvenil/diagnóstico , Biomarcadores/sangre , Niño , Análisis por Conglomerados , Marcadores Genéticos , Humanos , Sistema de Señalización de MAP Quinasas
6.
Biosens Bioelectron ; 80: 511-518, 2016 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-26890826

RESUMEN

TiO2 modified Co3O4 acicular nanotube arrays (ANTAs) have been fabricated in this study, showing a good performance in glucose detection. In the experiment, the precursor Co(CO3)0.5(OH)·0.11H2O acicular nanowire arrays (ANWAs) was first grown on the fluorine doped tin oxide (FTO) substrate by a hydrothermal method. Thereafter, the uniform pink precursor Co(CO3)0.5(OH)·0.11H2O ANWAs was completely converted to the black Co3O4 ANTAs thin film by alkaline treatment. After the decoration of TiO2, the TiO2/Co3O4 ANTAs electrode exhibits a much higher current response to glucose compared with the Co3O4 ANTAs. Importantly, this neotype composite structure of Co3O4 enhances the glucose sensing performance by increasing specific surface area, additional reactive sites and synergistic effect, which make the TiO2/Co3O4 glucose sensor show a high sensitivity of 2008.82 µA mM(-1) cm(-2), a fast response time (less than 5s) and a detection limit as low as 0.3396 µM (S/N=3). The TiO2/Co3O4 ANTAs modified electrode exhibits a high selectivity for glucose in human serum, against ascorbic acid and uric acid.


Asunto(s)
Técnicas Biosensibles , Glucemia/aislamiento & purificación , Nanotubos/química , Ácido Ascórbico/química , Cobalto/química , Humanos , Límite de Detección , Óxidos/química , Titanio/química , Ácido Úrico/química
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