RESUMEN
Schisandrin B is an active monomer of the Chinese magnolia vine (Schisandra chinensis) that can reduce transaminase activity in liver cells, inhibit lipid peroxidation, enhance antioxidant status, has protective effects in the liver and has antitumor effects. The present study investigated the potential protective effects of schisandrin B on the p53 signaling pathway in attenuating the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury (TSCI) in adult rats. Behavioral examination, inclined plate test and spinal cord water content were used to evaluate the protective effect of schisandrin B in TSCI rats. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor (NF)κB subunit p65 and tumor necrosis factor (TNF)α were examined using ELISA kits. Western blot analysis was performed to analyze the protein expression of caspase3 and phosphorylated (p)p53 in TSCI rats. In the present study, schisandrin B improved behavioral examination results and the maximum angle of inclined plate test, and inhibited spinal cord water content in rats with TSCI. Notably, schisandrin B reduced the activation of traumatic injuryassociated pathways, including SOD, MDA, NFκB p65 and TNFα, in TSCI rats. In addition, schisandrin B suppressed the TSCIinduced expression of caspase3 and pp53 in TSCI rats. These results indicated that schisandrin B may attenuate the inflammatory response, oxidative stress and apoptosis in TSCI rats by inhibiting the p53 signaling pathway in adult rats.
Asunto(s)
Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Lignanos/farmacología , Estrés Oxidativo/efectos de los fármacos , Compuestos Policíclicos/farmacología , Transducción de Señal/efectos de los fármacos , Traumatismos de la Médula Espinal/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antiinflamatorios/química , Biomarcadores , Caspasa 3/metabolismo , Ciclooctanos/química , Ciclooctanos/farmacología , Modelos Animales de Enfermedad , Lignanos/química , Masculino , FN-kappa B/metabolismo , Compuestos Policíclicos/química , Ratas , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: The purpose of this study was to evaluate comparatively, in women undergoing caesarean section under spinal anesthesia, the effectiveness of hyperbaric bupivacaine combined with 3 different adjuvants (fentanyl, clonidine, and dexmedtomidine) on quality of blockade and maternal and neonatal repercussions. METHOD: 84 patients undergoing elective surgeries under spinal anesthesia were randomized into 4 groups of 21 each, gB, gBF, gBC and gBD. Patients in groups gb, gBF, gBC and gBD were given bupivacaine alone, bupivacaine plus fentanyl (15.0 µg), bupivacaine plus fentanyl plus clonidine (75 µg), and bupivacaine plus dexmedetomidine (10 µg), respectively. Hemodynamic parameters evaluated were the onset and level of sensory block, perioperative analgesia, degree and recovery time of motor block, duration of analgesia, sedation, and maternal-foetal repercussions. RESULTS: The onset of blockade was significantly faster in groups with adjuvants clonidine and dexmedetomidine compared with gB and gBF. Patients in Groups gB and gBF reported pain during the perioperative period. Duration of analgesia was significantly higher in Group gBD and was comparable to gBC and time to motor block recovery was significantly higher in Group gBD. Sedation was significant in Group gBD and gBC. CONCLUSION: Addition of dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine provided adequate anesthesia and postoperative analgesia compared to fentanyl adjuvant without causing any significant side effects.
Asunto(s)
Bupivacaína/administración & dosificación , Clonidina/administración & dosificación , Dexmedetomidina/administración & dosificación , Fentanilo/administración & dosificación , Adyuvantes Anestésicos/administración & dosificación , Adulto , Anestesia Obstétrica/métodos , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Cesárea/métodos , Método Doble Ciego , Femenino , Humanos , Recién Nacido , Inyecciones Espinales , Dolor Postoperatorio/prevención & control , Embarazo , Adulto JovenRESUMEN
OBJECTIVE: To determine whether autophagy was involved in chondrocyte cells post Glucocorticoids (GCs) treatment. MATERIALS AND METHODS: LC3-GFP reporter plasmid transfection and western blotting analysis were conducted to determine the autophagic vesicles and autophagy-associated molecules in the N1511 chondrocyte cells post dexamethasone (Dex) treatment. And the N1511 cell viability was also determined by MTT assay. RESULTS: We found that autophagy was induced in the N1511 chondrocyte cells post treatment with Dex of 5 µM to 1 mM, and the autophagy-induction by Dex could be inhibited by 3 MA and RU486, a GC antagonist. And the autophagy induced by the high dose of Dex (200 µM or 1 mM) was associated with a reduction of N1511 cell viability. CONCLUSIONS: These results suggested that GCs could induce autophagy, as might contribute to the viability reduction of chondrocyte cells.
Asunto(s)
Autofagia/efectos de los fármacos , Condrocitos/efectos de los fármacos , Glucocorticoides/toxicidad , Animales , Autofagia/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Condrocitos/fisiología , Dexametasona/farmacología , Dexametasona/toxicidad , Glucocorticoides/farmacología , RatonesRESUMEN
Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.
Asunto(s)
Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Interferencia de ARN , Securina/metabolismo , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Securina/genética , Regulación hacia ArribaRESUMEN
Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.
Asunto(s)
Neoplasias de la Próstata/metabolismo , Interferencia de ARN , Securina/metabolismo , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proto-Oncogenes Mas , Securina/genética , Regulación hacia ArribaRESUMEN
Macrophage migration inhibitory factor (MIF) is a well-described proinflammatory mediator. MIF overexpression has been observed in many tumors and is implicated in oncogenic transformation and tumor progression. However, the molecular mechanisms responsible for regulating MIF expression remain poorly understood. In this study, we showed that the transcriptional repressor HBP1 (HMG box-containing protein 1) negatively regulates MIF expression. We first identified a large high-affinity HBP1 DNA-binding element at positions -811 to -792 from the transcriptional start site within the MIF promoter by computer analysis. Reporter analyses showed that this element was required for HBP1-mediated transcriptional repression. Furthermore, HBP1 associated with the MIF promoter in vivo and repressed endogenous MIF gene expression. Consistent with HBP1-mediated repression of MIF, low levels of HBP1 expression were associated with high levels of MIF expression in prostate cancer samples. Importantly, HBP1-mediated repression of MIF inhibited tumorigenic growth and invasion, and the repressive effect of HBP1 on tumorigenic growth and invasion could be partially rescued by the addition of recombinant MIF to the culture medium. Finally, prostate tumor samples with low HBP1 and high MIF expression were associated with a significant decrease in relapse-free survival. Taken together, these results indicated that HBP1 directly inhibited MIF gene transcription, and suggested that the loss of HBP1 expression or activity may contribute to the upregulation of MIF expression in prostate tumor tissue.