RESUMEN
In the early period of 21st century, RNA interference (RNAi) had emerged as one of the most important discoveries. This highly conserved endogenous gene silencing mechanism has been largely exploited as a powerful tool to determine biological functions of each gene. Both direct introduction of chemically synthesized small interference RNA (siRNA) and a plasmid or viral vectors encoding for siRNA can allow especially stable RNA knockdown. Recently, it has been widely used in the production of therapeutic drugs against hepatitis or immuno-deficiency viruses in human beings. Here, we provide a brief overview of the RNAi mechanism and the technology of RNAi on ischemic injury.
Asunto(s)
Isquemia/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Encéfalo/irrigación sanguínea , Vasos Coronarios/patología , Riñón/irrigación sanguínea , Hígado/irrigación sanguínea , Pulmón/irrigación sanguínea , RatonesRESUMEN
To determine whether the cardioprotection effect of fluvastatin mediates by toll-like receptor 4 (TLR4) signaling pathway, fifty Sprague-Dawley rats were randomly divided into five groups: sham operation group, ischemia/reperfusion (I/R) group, fluvastatin groups (high-dosage, medium-dosage, low-dosage, n = 10 in each group). Except sham operation group, the rest four groups of rats were artificially afflicted with coronary occlusion for 30 min, then reperfusion 2 h. Light microscope and transmission electronic microscope were used to observe structural changes of myocardium. RT-PCR was used to measure TLR4 mRNA expression level, TLR4 protein expression was detected by immunohistochemistry. Western blot was used to measure myocardial NF-κB protein level; ELISA was used to measure the level of TNF-α in myocardium. The results demonstrated that fluvastatin treatment markedly decreased ischemic injury caused by ischemia/reperfusion, and inhibited the expression levels of TLR4, TNF-α and NF-κB, all of which up-regulated by ischemia/reperfusion. Taken together, our results suggest that proper dosage of fluvastatin may have protective effect on the ischemic injury mediated by ischemia/reperfusion in the hearts, which might be associated with inhibition of TLR4 signaling pathway and inflammatory response during ischemia/reperfusion.
Asunto(s)
Cardiotónicos/uso terapéutico , Ácidos Grasos Monoinsaturados/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Indoles/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Cardiotónicos/farmacología , Ácidos Grasos Monoinsaturados/farmacología , Fluvastatina , Corazón/efectos de los fármacos , Corazón/fisiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Indoles/farmacología , Masculino , Miocardio/citología , Miocardio/patología , FN-kappa B/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: The aims of this study were to assess malnutrition risk in Chinese geriatric inpatients using Nutritional Risk Screening 2002 (NRS2002) and Mini-Nutritional Assessment (MNA), and to identify the most appropriate nutritional screening tool for these patients. DESIGN: Cross-sectional study. SETTING: Eight medical centres in Hubei Province, China. PARTICIPANTS: A total of 425 inpatients aged ≥70 years were consecutively recruited between December 2014 and May 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Nutritional risk was assessed using NRS2002, MNA, anthropometric measurements and biochemical parameters within 24 hours of admission. Comorbidities and length of hospitalisation were recorded. Nutritional parameters, body mass index (BMI) and length of hospital stay (LOS) were employed to compare MNA and NRS2002. Kappa analysis was used to evaluate the consistency of the two tools. RESULTS: The average age was 81.2±5.9 years (range, 70-98). The prevalence of undernutrition classified by NRS2002 and MNA was 40.9% and 58.6%, respectively. Patients undergoing malnutrition had lower BMI, haemoglobin, albumin and prealbumin (p<0.05), and longer LOS (p<0.05). The NRS2002 showed moderate agreement (κ=0.521, p<0.001) with MNA. Both tools presented significant correlation with age, BMI and laboratory parameters (p<0.001). In addition, a significant association between both tools and LOS was found (p<0.05). In addition, the NRS2002 was not different from MNA in predicting nutritional risk in terms of the area under the receiver operating characteristic curve (p>0.05). CONCLUSIONS: The results show a relatively high prevalence of malnutrition risk in our sample cohort. We found that NRS2002 and MNA were both suitable in screening malnutrition risk among Chinese geriatric inpatients.