RESUMEN
Sepsis induces critical myocardial dysfunction, resulting in an increased mortality. Gracillin (GRA) is a natural steroidal saponin, showing strong capacities of anti-inflammation, but its pharmacological effects on lipopolysaccharide (LPS)-induced acute cardiac injury still remain unclear. In this study, we attempted to explore if GRA was effective to attenuate cardiac injury in LPS-challenged mice and the underlying mechanisms. First, we found that GRA treatments markedly up-regulated the expression of miR-29a in cardiomyocytes. LPS-induced cytotoxicity in cardiomyocytes was significantly alleviated by GRA treatment, as evidenced by the improved cell viability and reduced lactate dehydrogenase (LDH) release. In addition, LPS-triggered apoptotic cell death was clearly ameliorated in cardiomyocytes co-treated with GRA. Notably, LPS-exposed cells showed significantly reduced expression of miR-29a, while being rescued by GRA treatment. In vivo, LPS apparently impaired cardiac function in mice, which was, however, alleviated by GRA administration. In addition, GRA markedly attenuated apoptosis in hearts of LPS-challenged mice by decreasing the expression of cleaved Caspase-3. LPS-triggered inflammatory response in cardiac tissues was also suppressed by GRA through blocking nuclear factor κB (NF-κB) signaling pathway. We also found that miR-29a expression was highly reduced in hearts of LPS-treated mice but was rescued by GRA pretreatment. Besides, miR-29a mimic alleviated LPS-induced apoptosis and inflammation in cardiomyocytes; however, LPS-caused effects were further accelerated by miR-29a. Of note, the protective effects of GRA on LPS-injured cardiac tissues were significantly abrogated by miR-29a suppression. In conclusion, our findings demonstrated that GRA exerted an effective role against LPS-induced acute cardiac injury through impeding apoptosis and inflammation regulated by miR-29a.
Asunto(s)
Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Lesiones Cardíacas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , MicroARNs/genética , Espirostanos/uso terapéutico , Animales , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Lesiones Cardíacas/genética , Lesiones Cardíacas/inmunología , Inflamación/genética , Inflamación/inmunología , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/inmunología , RatasRESUMEN
Pancreatic cancer is one of the most difficult clinical cases to diagnose with a very low 5-year survival rate of 5%, regardless of the advances made in both the medical and surgical treatment of the disease. One of the contributing factors for the high mortality rate seen of pancreatic cancer patients is the lack of effective chemotherapies, which is believed to be due to drug-resistance. Based on recent evidence, epithelial-mesenchymal transition (ETM) of pancreatic cancer cells has been found to be associated with the development of drug resistance and an increase in cell invasion. Therefore, we conducted the present study in order to investigate the regulatory effects of Golgi protein-73 (GP73) on PC. GP73 and EMT-related gene expressions in PC, along with the adjacent and chronic pancreatitis tissues were determined by means of RT-qPCR and Western blot analysis. Cultured PC cells were treated with pAdTrack-CMV, si-NC, GP73 overexpression, Si-GP73, Snail-siRNA and GP73 + Snail-siRNA. Cell invasion, migration and metastasis were measured in vitro and in vivo. The results revealed that the PC tissues and chronic pancreatitis tissues exhibited diminished E-cadherin expression and amplified GP73, N-cadherin, Vimentin and Snail expression. In response to GP73 gene silencing, PC cells presented with increased E-cadherin expression and decreased N-cadherin, Vimentin, Snail expression in addition to the inhibition of the number of invasive cells, tumor volume and number of liver lesions. These findings highly indicated that the overexpression of GP73 promotes cell invasion, migration and metastasis by inducing EMT in PC.
Asunto(s)
Transición Epitelial-Mesenquimal/fisiología , Predisposición Genética a la Enfermedad , Proteínas de la Membrana/metabolismo , Neoplasias Pancreáticas/metabolismo , Animales , Biomarcadores de Tumor , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , Ratones Desnudos , Invasividad Neoplásica , Neoplasias Experimentales , Neoplasias Pancreáticas/genética , Factores de Transcripción de la Familia Snail , Vimentina/genética , Vimentina/metabolismo , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To explore the effect of bile in inducing gastric mucosal injury in rats. METHODS: SD rats were divided into 4 groups, namely bile duct ligation group, duodenogastric reflux (DGR) group, DGR plus bile duct ligation group and normal control group. The pathological changes in the gastric mucosa and tight junction 3 months after gastrojejunostomy were observed and compared with the findings in the normal control rats. RESULTS: Compared with the rats in DGR plus bile duct ligation group, the rats in DGR group showed obvious gastric mucosal hyperemia, foveolar hyperplasia and severely impaired tight junction between the gastric mucosal cells. CONCLUSION: Bile plays an important role in gastric mucosal injury due to DGR.