RESUMEN
BACKGROUND: The lncRNA NKILA has been reported to interact with NF-κB and has an important role in various human diseases. However, the role of NKILA in myocardial ischaemic injury is still unknown. METHODS: We established cell and animal models of myocardial ischaemic injury. We confirmed our findings by overexpressing NKILA, silencing myocardin and using an NF-κB pathway inhibitor in a hypoxia/reoxygenation (H/R) model of H9c2 cells. An animal model of ischaemia-reperfusion (I/R) injury was established by LAD ligation. Overexpression of NKILA was achieved by adeno-associated virus (AAV) injection through the tail vein. Annexin-V/PI staining and flow cytometric analysis were performed to test cell apoptosis. ELISAs were used to determine the secretion of inflammatory factors. TTC, HE and TUNEL staining were performed to study myocardial pathological injury. qRT-PCR or Western blotting were used to test the expression levels of NKILA, myocardin, the NF-κB pathway and apoptosis-related proteins. RESULTS: H/R and I/R treatment significantly suppressed the expression of NKILA and activated the NF-κB pathway, resulting in the loss of myocardin. Overexpressing NKILA led to the suppression of the NF-κB pathway and successfully prevented the cell apoptosis and inflammatory responses caused by H/R stimulation in H9c2 cells. Silencing myocardin reversed the protective effect of NKILA and led to severe injury in the H9c2 cells that underwent H/R. Furthermore, the NF-κB pathway inhibitor BAY11-7028 reduced the H/R injury in H9c2 cells with little effect on NKILA expression. Similar results were confirmed in an animal model of myocardial I/R injury and showed that overexpression of NKILA inhibited I/R-triggered myocardial injury in vivo. CONCLUSION: NKILA enhanced the expression of myocardin via inhibiting the NF-κB signalling pathway and preventing cell apoptosis and the inflammatory response of cardiomyocytes, thus ameliorating myocardial I/R injury.
Asunto(s)
Isquemia Miocárdica/genética , Miocitos Cardíacos/fisiología , FN-kappa B/genética , Proteínas Nucleares/genética , ARN Largo no Codificante/genética , Transducción de Señal/genética , Transactivadores/genética , Animales , Apoptosis/genética , Línea Celular , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Hipoxia/genética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Spinal anesthesia (SA) is usually associated with hypotension in pregnant women. We sought to assess the influence of various maternal positions on SA-induced hypotension MATERIAL/METHODS: The study population comprised 99 women at full-term gestation scheduled for elective cesarean section. They were randomized into 3 equal groups: the LL group, in which the patient was placed in the full left-lateral position until the start of surgery with the Whitacre needle bevel oriented laterally; the LS group, in which the patient was placed in the full left-lateral position initially and then shifted to the left-tilt supine position with the needle bevel oriented laterally; and the CS group, in which the patient was initially placed in the full left-lateral position and then shifted to the left-tilt supine position with the needle oriented in the cephalad direction. RESULTS: The incidences of hypotension in the LL, LS, and CS groups were 9.7%, 54.8%, and 56.3%, respectively. Ephedrine requirements were lower in the LL group than in the LS group (P<0.01). CONCLUSIONS: The maternal position during the induction of anesthesia played an important role in the development of hypotension during cesarean delivery.
Asunto(s)
Amidas/administración & dosificación , Anestesia Epidural/métodos , Anestesia Raquidea/métodos , Cesárea/métodos , Hipotensión/etiología , Posición Supina/fisiología , Útero/irrigación sanguínea , Adulto , Anestesia Epidural/efectos adversos , Anestesia Raquidea/efectos adversos , Anestésicos Locales/efectos adversos , Presión Sanguínea , Femenino , Hemodinámica , Humanos , Bloqueo Nervioso , Embarazo , RopivacaínaRESUMEN
OBJECTIVE: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. METHODS: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68- positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. RESULTS: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. CONCLUSIONS: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/ M1 ratio are more accurate predictors for liver metastasis of colorectal cancer.