RESUMEN
Vascular dementia (VD) is one of the leading causes of neurological disorder following Alzheimer's disease. The present study evaluated the possible role of asiaticoside in the treatment of rats with VD and its inhibitory effects on autophagy in hippocampal tissues. Double ligation was used for permanent occlusion of the arteries, and spatial memory was assessed using the Tmaze test. Western blotting was used for determination of protein expression levels and H&E staining for histological analysis. Treatment of rats with VD with asiaticoside significantly alleviated the impairment in spontaneously altered behaviors and significantly reduced escape latency. VD mediated a decrease in distance travelled, swim time and number of platform crossings, whereas this was alleviated by asiaticoside. Furthermore, VDmediated hippocampal tissue damage was significantly alleviated by asiaticoside treatment (P<0.05), and asiaticoside alleviated formation of autophagosomes and markedly suppressed the number of primary lysosomes. In asiaticosidetreated rats, VDmediated increases in Beclin 1 and microtubuleassociated protein light chain 3 (LC3) II expression in the hippocampal tissues were alleviated. Asiaticoside treatment also prevented suppression of mammalian target of rapamycin (mTOR) phosphorylation in VD rat hippocampal tissues. Notably, the rapamycinmediated suppression of phosphorylatedmTOR, and elevation of Beclin 1 and LC3II expression in the rat hippocampus could not be alleviated by asiaticoside treatment. In conclusion, asiaticoside effectively prevented cerebral ischemiamediated cognitive impairment and neuronal damage in the rats. Moreover, autophagy was inhibited and the mTOR pathway was activated in rats with cerebral ischemia by asiaticoside treatment. Therefore, asiaticoside may warrant further study as a therapeutic agent for the treatment of dementia.
Asunto(s)
Autofagia/efectos de los fármacos , Memoria/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Triterpenos/farmacología , Enfermedad de Alzheimer/metabolismo , Animales , Autofagosomas/metabolismo , Beclina-1/metabolismo , Isquemia Encefálica , Disfunción Cognitiva/metabolismo , Demencia Vascular/tratamiento farmacológico , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto , Proteínas Asociadas a Microtúbulos/metabolismo , Neuronas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Asunto(s)
Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Periimplantitis/prevención & control , Periimplantitis/terapia , Titanio/farmacología , Aminas/administración & dosificación , Aminas/química , Aminas/farmacología , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Materiales Biocompatibles Revestidos/administración & dosificación , Materiales Biocompatibles Revestidos/química , Implantes Dentales , Estabilidad de Medicamentos , Humanos , Técnicas In Vitro , Masculino , Ensayo de Materiales , Oseointegración/efectos de los fármacos , Periimplantitis/microbiología , Porosidad , Conejos , Propiedades de Superficie , Titanio/administración & dosificación , Titanio/químicaRESUMEN
Glioblastoma (GBM) is the most prevalent primary malignancy of the central nervous system with obvious aggressiveness, and is associated with poor clinical outcome. Studies have indicated that calcium ion (Ca2+ ) can positively regulate the initiation of malignancy with regard to GBM by modulating quiescence, proliferation, migration and maintenance. Hippocalcin like-1 protein (HPCAL1) serves as a sensor of Ca2+ . However, the understanding of HPCAL1 activity in GBM is limited. The present study revealed that the gene HPCAL1 was up-regulated by Ca2+ in the tissues and cells of GBM. Ectopic expression of HPCAL1 promoted proliferation of cells. Exhaustion of HPCAL1 inhibited cell growth not only in vivo, but also in vitro. In addition, HPCAL1 enhanced the Wnt pathway by stimulating ß-catenin accumulation and nuclear translocation in GBM cells, while ß-catenin silencing significantly inhibited the proliferation and growth of the GBM cells. Our results showed that Ser9 phosphorylation of GSK3ß was significantly decreased after HPCAL1 knockdown in GBM cells, and knockdown of the gene GSK3ß in GBM cells enhanced cell proliferation and promoted transcription of the genes CCND1 and c-Myc. Furthermore, the phosphorylation of ERK was decreased in the cells with HPCAL1 knockdown, while it was promoted via overexpression of HPCAL1. The suppression or depletion of the gene ERK decreased proliferation triggered by overexpression of HPCAL1 and impaired transcription of the genes c-Myc and CCND1. These studies elucidate the tumour-promoting activity of HPCAL1. They also offer an innovative therapeutic strategy focusing on the HPCAL1-Wnt/ß-catenin axis to regulate proliferation and development of GBM.