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1.
PLoS Pathog ; 18(9): e1010782, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36121829

RESUMEN

Safe, passive immunization methods are required against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants. Immunization of chickens with antigen is known to induce specific IgY antibodies concentrated in the egg yolk and has a good safety profile, high yield of IgY per egg, can be topically applied, not requiring parenteral delivery. Our data provide the first evidence of the prophylactic efficacy of Immunoglobulin Y antibodies against SARS-CoV-2 in mice. Lohmann hens were injected with recombinant SARS-CoV-2 RBD protein; IgY-Abs were extracted from the eggs and characterized using SDS-PAGE. Antiviral activity was evaluated using plaque reduction neutralization tests. In additional experiments, IgY-RBD efficacy was examined in mice sensitized to SARS-CoV-2 infection by transduction with Ad5-hACE2 (mild disease) or by using mouse-adapted virus (severe disease). In both cases, prophylactic intranasal administration of IgY-Abs reduced SARS-CoV-2 replication, and reduced morbidity, inflammatory cell infiltration, hemorrhage, and edema in the lungs and increased survival compared to control groups that received non-specific IgY-Abs. These results indicate that further evaluation of IgY-RBD antibodies in humans is warranted.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Antivirales , Antivirales , COVID-19/prevención & control , Pollos , Femenino , Humanos , Inmunoglobulinas , Ratones
2.
Diagnostics (Basel) ; 10(6)2020 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-32575462

RESUMEN

Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological data of endometriosis patients and controls from NCBI's Gene Expression Omnibus, after a systematic search of multiple independent studies comprising 156 endometriosis patients and 118 controls to identify causative genes, risk factors, and potential diagnostic/therapeutic biomarkers. Comprehensive gene expression meta-analysis, pathway analysis, and gene ontology analysis was done using a bioinformatics-based approach. We identified 1590 unique differentially expressed genes (129 upregulated and 1461 downregulated) mapped by IPA as biologically relevant. The top upregulated genes were FOS, EGR1, ZFP36, JUNB, APOD, CST1, GPX3, and PER1, and the top downregulated ones were DIO2, CPM, OLFM4, PALLD, BAG5, TOP2A, PKP4, CDC20B, and SNTN. The most perturbed canonical pathways were mitotic roles of Polo-like kinase, role of Checkpoint kinase proteins in cell cycle checkpoint control, and ATM signaling. Protein-protein interaction analysis showed a strong network association among FOS, EGR1, ZFP36, and JUNB. These findings provide a thorough understanding of the molecular mechanism of endometriosis, identified biomarkers, and represent a step towards the future development of novel diagnostic and therapeutic options.

3.
Int J Pharm ; 554: 256-263, 2019 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-30423414

RESUMEN

Abundant efforts have recently been made to design potent theranostic nanoparticles, which combine diagnostic and therapeutic agents, for the effective treatment of cancer. In this study, we developed multifunctional magnetic gold nanoparticles (MGNPs) that are able to (i) selectively deliver the drug to the tumor site in a controlled-release manner, either passively or by using magnetic targeting; (ii) induce photothermal therapy by producing heat by near-infrared (NIR) laser absorption; and (iii) serve as contrast agents for magnetic resonance imaging (MRI) (imaging-guided therapy). The prepared MGNPs were characterized by different physical techniques. They were then coated and conjugated with polyethylene glycol (PEG) and doxorubicin (DOX) to form MGNP-DOX conjugates. The high efficacy of MGNP-DOX for combined chemo-photothermal therapy was observed both in vitro and in vivo. The effectiveness of MGNP-DOX as theranostic nanoparticles was confirmed by histopathological examination and immunohistochemical studies. Moreover, MGNP-DOX showed good potential as MRI contrast agents for guided chemo-photothermal synergistic therapy.


Asunto(s)
Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos , Nanopartículas de Magnetita , Fototerapia/métodos , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Terapia Combinada , Preparaciones de Acción Retardada , Doxorrubicina/farmacología , Portadores de Fármacos/química , Femenino , Oro/química , Humanos , Imagen por Resonancia Magnética , Ratones , Polietilenglicoles/química , Nanomedicina Teranóstica/métodos
4.
Artículo en Inglés | MEDLINE | ID: mdl-28250794

RESUMEN

Gastric ulcers are a major problem worldwide with no effective treatment. The objective of this study was to evaluate the use of manuka honey in the treatment of acetic acid-induced chronic gastric ulcers in rats. Different groups of rats were treated with three different concentrations of honey. Stomachs were checked macroscopically for ulcerative lesions in the glandular mucosa and microscopically for histopathological alterations. Treatment with manuka honey significantly reduced the ulcer index and maintained the glycoprotein content. It also reduced the mucosal myeloperoxidase activity, lipid peroxidation (MDA), and the inflammatory cytokines (TNF-α, IL-1ß, and IL-6) as compared to untreated control group. In addition, honey-treated groups showed significant increase in enzymatic (GPx and SOD) and nonenzymatic (GSH) antioxidants besides levels of the anti-inflammatory cytokine IL-10. Flow cytometry studies showed that treatment of animals with manuka honey has normalized cell cycle distribution and significantly lowered apoptosis in gastric mucosa. In conclusion, the results indicated that manuka honey is effective in the treatment of chronic ulcer and preservation of mucosal glycoproteins. Its effects are due to its antioxidant and anti-inflammatory properties that resulted in a significant reduction of the gastric mucosal MDA, TNF-α, IL-1ß, and IL-6 and caused an elevation in IL-10 levels.

5.
Oxid Med Cell Longev ; 2016: 3643824, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26770649

RESUMEN

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1ß, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1ß, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Miel , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Glucemia/metabolismo , Catalasa/metabolismo , Colesterol/sangre , Modelos Animales de Enfermedad , Conducta de Ingestión de Líquido/efectos de los fármacos , Etanol , Conducta Alimentaria/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glicoproteínas/metabolismo , Interleucina-1beta/sangre , Interleucina-6/sangre , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Coloración y Etiquetado , Úlcera Gástrica/patología , Superóxido Dismutasa/metabolismo , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/sangre , Aumento de Peso/efectos de los fármacos
6.
PLoS One ; 10(9): e0138917, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26422010

RESUMEN

Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4-6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 ß(IL-1ß) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea sponge Xestospongia testudinaria (100 mg/kg).


Asunto(s)
Antiinflamatorios , Mezclas Complejas , Edema/tratamiento farmacológico , Depuradores de Radicales Libres , Factores Inmunológicos , Xestospongia/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Mezclas Complejas/química , Mezclas Complejas/farmacología , Evaluación Preclínica de Medicamentos , Edema/inducido químicamente , Edema/patología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Océano Índico , Masculino , Ratas , Ratas Sprague-Dawley
7.
Artículo en Inglés | MEDLINE | ID: mdl-25214875

RESUMEN

Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE) on carbon tetrachloride- (CCl4-) induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg) of SMSE and silymarin (100 mg/kg) along with CCl4 (1 mL/kg, i.p., every 72 hr) for 14 days. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

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