Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats / 解剖学报

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

A Case of Aortoesophageal Fistula in Advanced Esophageal Cancer Treated with SB-Tube and TEVAR / 日本心臓血管外科学会雑誌

The patient is a 71-year-old man. After receiving chemoradiotherapy (CRTx) for an unresectable esophageal cancer, he developed sudden hematemesis during a follow-up examination. Subsequent imaging via contrast-enhanced computed tomography (CT) showed leakage of the contrast medium from the descending aorta into the esophagus. Consequently, an aortoesophageal fistula (AEF) was diagnosed and an emergency thoracic endovascular aortic stent graft repair (TEVAR) was scheduled. However, during the preparation for surgery, the patient vomited a large amount of blood and went into cardiopulmonary arrest. Following the administration of cardiopulmonary resuscitation, a Sengstaken-Blakemore tube (SB-tube) was inserted intranasally to control bleeding and TEVAR was performed to save his life. Although a gastrostomy was necessary after the surgery, the patient was transferred from the hospital on the 32nd day without any complications. Nonetheless, his general condition deteriorated as the cancer progressed and he died on the 103rd postoperative day. It is generally reported that the risk for esophageal perforation is 10-20% in CRTx for unresectable esophageal cancer. Although issues regarding the long-term prognosis of patients treated with TEVAR have been highlighted in recent years, there have also been reports of life-saving cases following its use; in this case, the patient was discharged home after SB-tube insertion and TEVAR with prompt treatment, resulting in his life being prolonged for an estimated 3 months.

The effect of inhibiting p38 MAPK on the expression of genes related to enamel development in mice / 口腔疾病防治

Objective@#To study the effect of p38 mitogen activated protein kinase (p38 MAPK) on the expression of genes related to enamel development in the enamel epithelium and to provide a basis for the study of the molecular mechanism of enamel development.@*Methods@#The p38 MAPK-specific inhibitor SB203580 dissolved in DMSO was added to the culture medium of mouse mandibular molar tooth germs in vitro as experiment group, and mouse mandibular molar tooth germs treated with the same amount of DMSO were used as control group. Western blot was used to detect the protein expression level of phosphorylated p38 (p-p38) in the enamel epithelium. Real-time PCR was used to detect the mRNA expression levels of runt-related transcription factor 2 (Runx2), osteoblast-specific transcription factor (Osx), ameloblast markers odontogenic ameloblast associated protein (ODAM), amelotin (AMTN), matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4) in the enamel epithelium. @*Results @# Western blot results showed that under the action of the inhibitor SB203580, the phosphorylation level of p38 MAPK in mouse enamel epithelium decreased, and the difference was statistically significant (P < 0.05). Real-time PCR results showed that the expression levels of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20, and KLK4 in the SB203580 group were lower than those in the control group, and the difference was statistically significant (P < 0.05).@*Conclusion@#The p38 MAPK signaling pathway can mediate enamel development by regulating the expression of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20 and KLK4 in the mouse enamel epithelium.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective To investigate the effect and underlying mechanisms of p38 mitogenactivated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.Methods Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group,APILP group,and SB203580 treatment (SB) group.APILP model was induced by retrograde injection of 5％ sodium taurocholate into the biliary-pancreatic duct.SB203580 administration (10 mg/kg body weight,intraperitoneal injection) was performed 0.5 h before surgery.All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point.Animals were sacrificed at 12 h after the induction of APILP,then the blood and tissue samples were harvested.Serum levels of AMY and TNF-α were analyzed.Histopathological changes of maternal pancreas and fetal lung were observed and evaluated.The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence.The expression ofp-p38MAPK,p38MAPK,TNF-α and ICAM-1 was determined by Western blot.One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.Results The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7871.3±623.5) vs (1 915.3±452.3),(193.8±25.4) vs (107.0±±13.3),(P＜0.05)].Obvious pathological changes presented in matemal pancreas and fetal lung after the attack of APILP,and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56),(2.50±0.53) vs (0.88±0.64),(P＜0.05)].The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80),(53.38±8.30) vs (11.75±3.33);P＜0.05)].In addition,the expression and nuclear translocation were pervasive in fetal lungs in the APILP group.Furthermore,the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)],TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)],ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P＜0.05).However,with the pre-administration of SB203580,the pathological scores of matemal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P＜0.05),as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P＜0.05).The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P＜0.05) and fewer nuclear translocation was observed in the SB group.Interestingly,the expression levels of p-p38MAPK (0.2578±0.0170),TNF-α (0.3240±0.0326),ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P＜0.05).Conclusions P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury;SB203580 administration could significantly attenuate fetal lung injury induced by APILP,which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

Inhibition of the TGF-β/Smad3 signaling pathway by SB431542: A study of the intervention effect of SB431542 on silicotic fibrosis in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the intervention effect of SB431542, which inhibits the TGF-β/Smad3 signaling pathway, on silicotic fibrosis in rats.@*Methods@#A total of 40 specific pathogen-free Sprague-Dawley rats were divided into normal saline control group, model group, SB431542 inhibitor group, and SB431542 inhibitor control group using a random number table, with 10 rats in each group. All rats except those in the normal saline control group were given non-exposed single intratracheal instillation of free silicon dioxide dust suspension 1 mL (50 mg/mL) ; the rats in the SB431542 inhibitor group were given intraperitoneal injection of SB431542 (5 mg/kg) on days 7 and 30 after dust exposure, those in the SB431542 inhibitor control group were given intraperitoneal injection of SB431542 cosolvent (5 mg/kg) on days 7 and 30 after dust exposure, and those in the normal saline control group were given intratracheal instillation of an equal volume of normal saline (5 mg/kg). On day 60 after dust exposure, the paraffin-embedded section of the right upper lobe of lung was collected for HE staining; the left upper lobe of lung was collected to measure the mRNA levels of fibronectin (FN) , collagen type I (COL-I) , and collagen type III (COL-III) by quantitative real-time PCR; the right inferior lobe of lung was collected to measure the protein levels of FN, COL-I, COL-III, phosphorylated Smad3 (p-Smad3) , and Smad3.@*Results@#Compared with the normal saline control group, the model group had nodules with various sizes in lung tissue, with rupture of some alveolar septa, emphysema changes, and pulmonary interstitial fibrosis, as well as significant increases in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . Compared with the SB431542 inhibitor control group, the SB431542 inhibitor group had a relatively complete structure of lung tissue without marked nodules and with a small amount of exudate in alveolar space and the lumen of bronchioles, as well as significant reductions in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . There were no significant differences in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 between the model group and the SB431542 inhibitor control group (P>0.05) .@*Conclusion@#SB431542 exerts an intervention effect on silicotic fibrosis by blocking the TGF-β/Smad3 signaling pathway and reducing the expression of the downstream fibrosis factors FN, COL-I, and COL-III.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective@#To investigate the effect and underlying mechanisms of p38 mitogen-activated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.@*Methods@#Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group, APILP group, and SB203580 treatment (SB) group. APILP model was induced by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. SB203580 administration (10 mg/kg body weight, intraperitoneal injection) was performed 0.5 h before surgery. All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point. Animals were sacrificed at 12 h after the induction of APILP, then the blood and tissue samples were harvested. Serum levels of AMY and TNF-α were analyzed. Histopathological changes of maternal pancreas and fetal lung were observed and evaluated. The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence. The expression of p-p38MAPK, p38MAPK, TNF-α and ICAM-1 was determined by Western blot. One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.@*Results@#The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7 871.3±623.5) vs (1 915.3±452.3), (193.8±25.4) vs (107.0±13.3), (P<0.05)]. Obvious pathological changes presented in maternal pancreas and fetal lung after the attack of APILP, and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56), (2.50±0.53) vs (0.88±0.64), (P<0.05)]. The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80), (53.38±8.30) vs (11.75±3.33); P<0.05)]. In addition, the expression and nuclear translocation were pervasive in fetal lungs in the APILP group. Furthermore, the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)], TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)], ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P<0.05). However, with the pre-administration of SB203580, the pathological scores of maternal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P<0.05), as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P<0.05). The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P<0.05) and fewer nuclear translocation was observed in the SB group. Interestingly, the expression levels of p-p38MAPK (0.2578±0.0170), TNF-α (0.3240±0.0326), ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P<0.05).@*Conclusions@#P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury; SB203580 administration could significantly attenuate fetal lung injury induced by APILP, which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

The Application Methods of Mitogen-activated Protein Kinase Signal Pathway Inhibitors SP600125 and SB203580 in Long-term in Vivo Experiments / Métodos de aplicación de los inhibidores SP600125 y SB203580 de la vía de señalización de la proteína quinasa activada por mitógeno en experimentos in vivo a largo plazo

ABSTRACT Objective: To explore the application methods of mitogen-activated protein kinase signal pathway inhibitors SP600125 and SB203580 in long-term in vivo experiments. Methods: A total of 55 healthy New Zealand rabbits were randomly divided into blank control group, model control group, SP low dose group, SP high dose group, SP blank group, SB low dose group, SB high dose group, SB blank group, dimethyl sulfoxide (DMSO) control group, DMSO blank group, and positive control group. Since the first day of the experiment, each group was administered the corresponding treatment for four weeks continuously. Then, the myocardial c-Jun N-terminal kinase (JNK) and the total protein of p38, protein phosphorylation and its gene expression levels were detected. Results: After intravenous treatment with adriamycin, the myocardial phosphorylate-JNK (p-JNK) and phosphorylate-p38 (p-p38) levels in all groups were increased to varying degrees, of which the model control group increased the most significantly (p < 0.05). Compared with the model control group, the myocardial p-JNK and p-p38 increased more slowly in the SP low dose group, SP high dose group, SB low dose group, SB high dose group and positive control group (p < 0.05), of which the increase in the SP high dose group and the SB high dose group was the slowest (p < 0.05). After four weeks, the total protein and messenger ribonucleic acid of the myocardial JNK and p38 in all groups had no statistically significant difference (p > 0.05). Conclusion: The continuous intravenous injection of SP600125 and SB203580 for four weeks significantly reduced the protein phosphorylation levels of JNK and p38, which provides a practical avenue for the long-term study in vivo.

RESUMEN Objetivo: Explorar los métodos de aplicación de los inhibidores SP600125 y SB203580 de la vía de señalización de la proteína quinasa activada por mitógeno en experimentos in vivo a largo plazo. Métodos: Un total de 55 conejos sanos de Nueva Zelandia fueron divididos aleatoriamente en los grupos siguientes: grupo de control en blanco, grupo de control modelo, grupo de dosis baja SP, grupo de dosis alta SP, grupo en blanco SP, grupo de dosis baja SB, grupo de dosis alta SB, grupo en blanco SB, grupo de control dimetilsulfóxido (DMSO), grupo en blanco DMSO, y grupo de control positivo. Desde el primer día del experimento, a cada grupo se le administró el tratamiento correspondiente por cuatro semanas continuas. Entonces, se detectaron la quinasa c-Jun N-terminal (JNK) miocárdica y la proteína p38 total, así como la fosforilación proteica y sus niveles de expresión génica. Resultados: Después del tratamiento intravenoso con adriamicina, los niveles de fosfo-JNK (p-JNK) y fosfo-p38 (p-p38) del miocardio aumentaron en todos los grupos en diversos grados, siendo el aumento del grupo de control modelo el más significativo (p < 0.05). En comparación con el grupo de control modelo, p-JNK y p-p38 miocárdicos aumentaron más lentamente en el grupo de dosis baja SP, el grupo de dosis alta SP, el grupo de dosis baja SB, el grupo de dosis alta SB, y el grupo de control positivo (p < 0.05). De estos, el aumento en el grupo de dosis alta SP y el grupo de dosis alta SB fue el más lento (p < 0.05). Después de cuatro semanas, la proteína total y el ácido ribonucleico mensajero de JNK y p38 miocárdicos en todos los grupos, no tuvieron diferencias significativas (p > 0.05). Conclusión: La inyección intravenosa continua de SP600125 y SB203580 durante cuatro semanas redujo significativamente los niveles de fosforilación proteica de JNK y p38, lo que proporciona una vía práctica para el estudio a largo plazo in vivo.

Mucosal Changes in the Small Intestines in Portal Hypertension: First Study Using the Pillcam SB3 Capsule Endoscopy System

BACKGROUND/AIMS: To evaluate patients with portal hypertension (PH) of varied etiologies for portal hypertensive enteropathy (PHE) using the PillCam SB3 capsule endoscopy (CE) system. METHODS: Consecutive patients with PH presenting with unexplained anemia and/or occult gastrointestinal bleeding were evaluated using the PillCam SB3 CE system. Abnormal findings were categorized as vascular or non-vascular. The patients with ongoing bleeding caused by PHE were treated. The correlation of the CE scores of PHE with the clinical, laboratory, and endoscopic features was determined. RESULTS: Of the 43 patients included in the study, 41 (95.3%) showed PHE findings. These included varices (67.4%), red spots (60.5%), erythema (44.2%), villous edema (46.5%), telangiectasia (16.3%), and polyps (16.3%). The CE scores varied from 0 to 8 (mean±standard deviation, 4.09±1.8). Five patients (11.6%) showed evidence of ongoing or recent bleeding due to PHE. Three of these five patients underwent endotherapy, and one patient underwent radiological coil placement. CONCLUSIONS: The PillCam SB3 CE system revealed a high prevalence of PHE in the patients with PH. Using this system, evidence of bleeding due to PHE was found in a small but definite proportion of the patients.

Application of Flush Knife and SB Knife in Peroral Endoscopic Myotomy for Treatment of Achalasia / 胃肠病学

Background:Peroral endoscopic myotomy (POEM) has been widely used in treatment of achalasia,and the efficacy is satisfactory.However,POEM is associated with high level of technical difficulty and high incidence of complications.Aims:To investigate the efficacy and safety of Flush knife and SB knife in POEM for treatment of achalasia.Methods:A total of 111 achalasia patients who had undergone POEM from April 2013 to April 2017 at Renmin Hospital of Wuhan University were enrolled,and were divided into Flush knife group,SB knife group and Dual knife group.Procedure-related parameters,complications,and follow-up data were compared among the three groups.Results:All the 111 patients underwent POEM successfully.The mean procedure time,mean frequency of hemostasis and mean frequency of device exchange were significant different among Flush knife group,SB knife group and Dual knife group (P all ＜ 0.05).Further comparisons showed that the above-mentioned procedure-related indices were significantly lower in Flush knife group and SB knife group than in Dual knife group (P all ＜ 0.05).The incidence of complications was significant different among the three groups (P =0.005).Further comparisons showed that incidence of complications was significantly lower in SB knife group than in Dual knife group (P =0.011),however,no significant difference was found between Flush knife group and Dual knife group (P =0.056).No significant difference in surgery success rate was found among the three groups (P ＞0.05).Conclusions:Flush knife and SB knife in POEM can shorten the procedure time and achieve similar success rate when compared with conventional Dual knife.

FlaA gene deletion of LM90 SB2 inducing sheep encephalitis and the influence on virulence / 中国人兽共患病学报

The flagellin of Listeria monocytogenes is encoded by flaA gene;there is no detail report about the influence of flaA gene on the virulence of LM90 SB2.FlaA gene-deleted strain was constructed successfully with recombination technology.The influence of FlaA on LM90 SB2 virulence was evaluated by motility,BF formation,LD50,etc.Results showed that the colony morphology did not change,gene-deleted strain still had good genetic stability,but its growth was slow and the motility was decreased in the environment at 25 ℃,the morphological structure of the mutant BF was looser and incomplete,LD50 was increased from 4.27 × 106 cfu to 1.62 × 107 cfu.Results indicated that the flaA gene affected the flagellar formation of LM90 SB2 significantly,the ability of the BF formation and the virulence of the flaA deleted strain were decreased obviously.

Expression and clinical significance of B7-H3 and IL-21 in serum of patients with HBV associated hepatocellular carcinoma / 中国免疫学杂志

Objective:To investigate the expression and clinical significance of B7-H3 and IL-21 in serum of patients with HBV-related primary liver cancer.Methods: Gathering 121 cases of HBV-related patients,50 cases of primary hepatic carcinoma of them were considered as hepatic carcinoma group,71 cases of benign group including 12 cases with acute hepatitis,21 cases of chronic moderate to severe hepatitis,20 cases of compensatory phase cirrhosis,18 cases of decompensated cirrhosis and 20 cases of healthy persons in the same period as normal control.The content of serum B7-H3 and IL-21 were detected by ELISA.HBV DNA quantitative results were analyzed by Quantitative Real-time PCR.Results: The levels of B7-H3 and IL-21 in patients with primary hepatic carcinoma were (207.60±57.16)ng/ml and(2 357.28±805.01)pg/ml,respectively,which were significantly higher than those of the normal control subjects(P<0.001).Comparison with the normal control subjects,the content of B7-H3 and IL-21 in serum of patients with different clinical types in the benign group increased significantly(P<0.001).B7-H3 and IL-21 were positively associated with each other in serum of patients with HBV-related primary liver cancer.The expression of sB7-H3 was not significantly correlated with the degree of HBV DNA replication.The expression of IL-21 was correlated with HBV DNA replication in patients with HBV associated hepatocellular carcinoma,but was not significantly correlated with the degree of HBV DNA replication.Conclusion: HBV-related primary hepatic carcinoma express sB7-H3 and IL-21 with high level.The continuous high expression of sB7-H3 and IL-21 in the body may be related to the development and prognosis of the patients.

Effects of SB203580 on biological functions of human extravillous trophoblast cells under oxidative stress / 上海交通大学学报（医学版）

Objective · To investigate the effects of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 on biological function changes of human extravillous trophoblast cells induced by hypoxia/re-oxygenation (H/R). Methods · In-vitro cultured early pregnancy villus explants and human extravillous trophoblast cell line HTR8/SVneo were assigned to 4 groups according to different interventions, i.e. control group, SB203580 group (p38 MAPK inhibition), H/R group (simulation of preeclampsia by the oxidative stress model), and SB203580+H/R group. The effects of SB203580 on biological functions of human extravillous trophoblast cells under oxidative stress in early pregnancy villus explants were observed. Protein expression and phosphorylation of p38 MAPK in HTR8/SVneo cells were measured with Western blotting. Cell migration and invasion were observed with Transwell migration and Matrigel invasion assay, respectively. Gelatin zymography was used to measure the activity of matrix metalloproteinase (MMP) -2/9 in supernatant. ELISA was used to detect the levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). Results · SB203580 could promote the exogenous migration of human extravillous trophoblast cells in early pregnancy villus explants under oxidative stress. H/R could decrease the migration and invasion of HTR8/SVneo cells , and increase the phosphorylation level of p38 MAPK in HTR8/SVneo cells and the secretion of sFlt-1 and sEng. SB203580 could increase the activity of MMP2/9 in supernatant and cell migration and invasion, decrease the phosphorylation level of p38 MAPK in HTR8/SVneo cells under oxidative stress and the secretion of sFlt-1 and sEng. Conclusion · SB203580 can protect biological functions of human extravillous trophobalst cells under oxidative stress.

Effect of P38MAPK pathway on autophagy in rat hippocampus following cerebral ischemic postcoditioning / 西安交通大学学报(医学版)

Objective To explore the mechanism of ischemic postconditioning in relieving cerebral ischemia reperfusion (IR) by regulating autophagy through P38MAPK pathway.Methods Cerebral ischemia reperfusion model was established by using modified Pulsinelli four-vessel occlusion (4-VO).Totally 128 male SD rats were divided into 4 groups randomly:control group (sham),cerebral ischemia reperfusion model group (CIR),cerebral ischemic postconditioning group (CIP),and cerebral ischemic postconditioning + P38MAPK inhibitor group (SB203580 group).Each group was subdivided into four time points:6 h,24 h,48 h,and 72 h.The morphological changes of the hippocampus CA1 area neurons at each time point and the number of surviving nerve cells were detected with HE staining.The expression of the hippocampus CA1 area phosphorylated P38MAPK and the autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with immunohistochemistry.The protein content of the hippocampus phosphorylated P38MAPK and autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with Western blotting.Results Compared with those in sham group,the damage of rats' hippocampal neuron structure and the survival rate of neurons at each time point decreased in CIR group,the expressions of p-P38MAPK,LC3-Ⅱ and Beclin-1 increased.Compared with those in CIR group,in CIP and SB203580 groups the structure of rats hippocampal neurons was improved,the survival rate of neurons increased,the expression of p-P38MAPK decreased and the expressions of LC3-Ⅱ and Beclin-1 increased at each time point.Compared with CIP group,SB203580 grouphad improved structure of rats' hippocampal neurons,increased survival rate of neurons,decreased expression of p-P38MAPK,and increased expressions of LC3-Ⅱ and Beclin-1 at each time point.Conclusion Cerebral ischemic postconditioning through inhibiting P38MAPK pathway can regulate autophagy and exert its nerve-protective effect.

Agreement between international classification of disease (ICD) and cause of death and associated conditions (CODAC) for the ascertainment of cause of stillbirth (SB) in the rural areas of north India.

International Classification of Diseases-10 th version (ICD-10) has been used to ascertain the cause of death but its use for stillbirths (SBs) is limited. Cause of Death and Associated Conditions (CODAC) as a detailed system expected to provide the exact cause of SB, so a community-based study was planned to study the level of agreement between ICD-10 and CODAC for ascertaining the cause of SB. A verbal autopsy (VA) tool was used to collect the information and then the cause of each SB was assigned using ICD-10 and CODAC separately. Each tool was used for 87 SBs and found that prolonged singleton labor, maternal pregnancy induced hypertension (PIH), and central nervous system (CNS) related congenital malformations were considered the top three causes. There was a significant agreement between ICD-10 and CODAC but the latter offers a scope to delineate the causes more precisely due to its hierarchal nature.

Papel de receptores CXCR2 na mucosite intestinal induzida por Irinotecano

INTRODUÇÃO: O irinotecano é um antineoplásico usado no tratamento de primeira e segunda linha d o câncer colorretal . No entanto, um importante efeito colateral associado ao irinotecano, a mucosite intestinal, tem impactado negativamente n a qualidade de vida dos pacientes e n o sucesso terapêutico. Trabalhos anteriores demonstraram que na patogênese da mucosite intestinal há a participação de mediadores pró - inflamatórios, como IL - 1, IL - 18, IL - 33, óxido nítrico dentre outros, cuja modulação leva à redução do infiltrado neutrofílico no intestino e mel hora do dano tecidual. Entretanto, o papel de receptores de quimiocinas, como o CXCR2, importante s no recrutamento de neutrófilos, ainda não fo ram investigado s no contexto da mucosite. OBJETIVOS: Avaliar o papel d e receptores CXCR2 n a mucosite intestinal i nduzida p el o Irinotecano. MÉTODOS: Camundongos C57BL/6 machos, 18 - 25g, foram divididos em grupos (n=6), administrados por 4 dias com salina (5mL/kg, i.p) ou com irinotecano (75, 90, 105 ou 120 mg/kg, i.p). A dose de 120 mg/kg foi a que melhor reproduziu o quadro inflamatório característico da mucosite , sendo então utilizada nos ensaios posteriores em associação ao SB225002 , um antagonista de receptores CXCR2 . Os animais foram analisados quanto ao peso corpóreo , escores de diarreia, contagem de leucócitos. A pós a eutanásia, uma amostra de intestino foi coletada para análise histopatológica e morfométrica, dosagem de mieloperoxidase e níveis de IL - 1β , IFN - γ e KC . Além disso, o comprimento do intestino delgado foi mensurado , bem como o peso do conteúdo sólido . Avaliou - se também a bacteremia. Adicionalmente, realizou - se a quantificação dos re ceptores CXCR2 e CCR2, além do ensaio de quimiotaxia in vitro de neutrófilos isolados de camundongos tratados com IRI ou com IRI+SB225002. (Protocolo CEPA 58/14)...

INTRODUCTION: Irinotecan is an anticancer agent used in first and second line treatment protocols for colorectal cancer. However, a major side effect associated with irinotecan, intestinal mucositis, has negatively impacted on patient’s quality of life and limiting the therapeutic outcome. The literature reports the involvement of several inflammatory mediators in the pathogenesis of intestinal mucositis, including IL - 1, IL - 18, IL - 33, nitric oxide and several others, whose pharmacological inhibition prevents neutrophil infiltration and leads to mucositis improvement. However, the role of chemokine receptors that are important to neutrophil recruitment, such as CXCR2, in intestinal mucositis is unknown. AIMS: To study the role of CXCR2 receptors in the pathogenesis of irinotecan - induced intestinal mucositis. METHODS: M ale C57BL /6 mice (n = 6) were divided into groups and injected with either saline (5ml / kg, ip) or irinotecan (75, 90, 105 or 120 mg/kg ip) for 4 days. The dose of 120 mg / kg reproduce d the inflammatory condition of mucositis, so it was used in association with SB225002, a CXCR2 antagonist. Body mass variation, diarrhea scores and leukocyte count were recorded. Following euthanasia, intestinal samples were collected for histopathological analysis, mieloperoxidase activity (MPO), IL - 1β, KC and IFN - γ levels. In addition, the length of the small intestine was measured so was the weight of its solid contents. Bacteremia was further carried out. Additionally, we measured the expression of CXCR2 and CCR2 receptors on neutrophils surface. We also performed the in vitro chemotaxis assay, using neutrophils isolated from bone marrow of mice treated with IRI or IRI + SB225002 (Study approval number: 58/14)...

The effects of P38MAPK inhibitor SB203580 on TEMT of HK-2 cells / 天津医药

Objective To observe the effects of different concentrations of SB203580, the inhibitor of P38MAPK, in process of high glucose (GS)-induced renal tubular epithelial-myofibroblast transdifferentiation (TEMT). Methods The cultured human renal tubular epithelial cells (HK-2) were divided into control group (5.5 mmol/L GS), GS (30 mmol/L GS) group and different concentrations of SB203580 (30 mmol/L GS +5, 10, 20 and 30 μmol/L SB203580) groups. The treat?ments were for 48 hours. MTT assay was used to observe cell proliferation. The median inhibiting concentration (IC50) was cal?culated. Western blot assay was used to detect the expressions of P38MAPK, P-P38MAPK andα-smooth muscle actin (α-SMA) in control group, high-glucose group and S30 group. The expression ofα-SMA was also detected by the method of im?munofluorescence. Results 1.Compared with control group, there was no significant inhitory effect on proliferation rate in DMSO group (P>0.05). There were increased HK-2 cells in high glucose group and S5group (P0.05). 3. Compared with control group, the expression ofα-SMA was signifi?cantly increased in high glucose group and S30 group (P<0.05). Compared with high glucose group, the expression of α-SMA was significantly decreased in S30 group (P < 0.05). Conclusion The 30 mmol/L GS can lead to TEMT in HK-2 cells. The more suitable inhibitory concentration of SB203580 in the process of TEMT is 30μmol/L. SB203580 can slow down the process of TEMT by inhibiting P38MAPK activation and inhibiting proliferation and the expression ofα-SAM s of HK-2 cells.

Correlations between the soluble form of B7-H3 and the cytokines of IL-17 and IL-8 in patients with primary hepatocellular carcinoma and their clinical values for early diagnosis of hepatocellular carci-noma / 中华微生物学和免疫学杂志

Objective To investigate the correlations between the soluble form of B7-H3 ( sB7-H3) and the cytokines of IL-17 and IL-8 in serum samples from patients with primary hepatocellular carcino-ma ( HCC) and to evaluate their clinical values for early diagnosis of HCC.Methods Serum samples were collected from 63 patients with HCC and 50 healthy subjects.The expression of sB7-H3, IL-17 and IL-8 in serum samples were detected by ELISA.Receiver operating characteristic ( ROC) curve was generated to an-alyze the diagnostic values of sB7-H3, IL-17 and IL-8 for hepatoma.The logistic regression model was used to predict the probability of hepatoma by using sB7-H3, IL-17 and IL-8 in combination.Results The levels of sB7-H3, IL-17 and IL-8 in serum samples collected from the patients with HCC were significantly higher than those from healthy subjects.A positive correlation was found between the levels of sB7-H3 and IL-17 in serum samples from patients with HCC.No correlation was found between sB7-H3 and IL-8.A negative cor-relation was found between the levels of IL-17 and IL-8 in serum samples from patients with HCC.ROC curve analysis showed that the area under the curve (AUC) of sB7-H3, IL-17 and IL-8 were 0.832, 0.657 and 0.953, respectively, indicating the statistical significance of them for the diagnosis of HCC.The logistic regression showed that the AUC, diagnostic sensitivity and specificity of the regression model PRE in the pre-diction of HCC were 0.960, 91.30% and 94.29%, respectively, which was much better than using the three indicators alone.Conclusion The levels of sB7-H3 were positively correlated to the levels of IL-17 in serum samples from patient with HCC.The logistic regression model of combination of sB7-H3, IL-17 and IL-8 obtained in this study could be used for early clinical diagnosis of HCC in the future.

The efficacy of SB knife in peroral endoscopic myotomy for achalasia / 中华消化内镜杂志

Objective To investigate the efficacy and safety of SB( stag beetle) knife in peroral en?doscopic myotomy( POEM) for achalasia( AC) . Methods A total of 58 cases of AC treated with POEM at department of gastroenterology of the People′s Hospital of Wuhan University from January 2013 to December 2014 were randomly divided into two groups,SB knife group and Dual knife group by using random number table, 29 patients in each group. The complications and therapeutic effects were analyzed. Results All 58 patients with achalasia successfully completed POEM. There were no significant complications in SB knife group such as subcutaneous emphysema, perforation or bleeding.But there were 4 cases of subcutaneous em?physema and 4 cases of bleeding occurred in Dual knife group.The overall incidence of complications was sig?nificantly lower in SB group than that in Dual knife group[0 VS 27?6%(8/29), P0?05). Conclusion SB knife is safe and effective for achalasia with POEM, which can effectively shorten the operation time and reduce the inci?dence of complications.

Expression and clinical signiifcance of sB7-H3 and cytokines in the bronchoalveolar lavage lfuid in children with refractory Mycoplasma pneumoniae pneumonia / 临床儿科杂志

Objective To explore the level of expression, clinical signiifcance of sB 7-H 3 in the bronchoalveolar lavage lfuid (BALF) of refractory Mycoplasma pneumoniae (MP) pneumonia (RMPP) in children and the relationship between sB7-H3 and various cytokines. Methods The BALF of forty-three hospitalized children with RMPP (RMPP group) were collected for the diagnosis and treatment. Thirteen cases were lavaged only once and the other thirty cases had collected the BALF twice. The BALF of iffteen hospitalized children with bronchial foreign body were collected as control group. The expression levels of sB 7-H 3 , IL-1β, IL-2 and IL-36 in the BALF were detected by enzyme-linked immunosorbent assay. The expression levels of sB 7-H 3 , IL-1β, IL-2 and IL-36 in the BALF at the acute phase were compared with control group and the group after treatment. Analyzed the correlation between the level of sB 7-H 3 and IL-1β, IL-2 , IL-36 in the BALF of RMPP children at acute stage. Results The levels of sB 7-H 3 , IL-1β and IL-36 in the BALF of the ifrst lavage group were higher than those of single lavage group and control group (all P0 . 05 ). The levels of sB 7-H 3 had positive correlation with the levels of IL-1β, IL-2 and IL-36 (all P<0 . 001 ). Conclusions sB 7-H 3 may control the secretion of IL-1β, IL-2 and IL-36 , and participate in immune response and lung injury after MP infection, which may lead to occurrence and development of RMPP.

Resección hepática asistida con radiofrecuencia bipolar: primeras experiencias con el Surtron SB / Bipolar radiofrequency-assisted liver resection and first experiences with Surtron SB equipment

Las resecciones primarias y secundarias del hígado tienen como uno de sus mayores dilemas el sangrado transoperatorio. La introducción de los equipos de radiofrecuencia, en particular el Surtron SB, comienza a dar resultados alentadores. Se presentan las primeras 8 experiencias cubanas con resecciones menores y mayores realizadas con este equipo. Siete de estos pacientes tenían metástasis y uno un hepatocarcinoma. Se practicaron 2 resecciones regladas y 6 atípicas, durante las cuales no hubo complicaciones y solo un paciente necesitó transfusión sanguínea.

Primary and secondary liver resections have transoperative bleeding as one of its major dilemmas. The introduction of radiofrequency equipment, mainly Surtron SB, begins to bring about encouraging results. The first eight cases of minor and major resections in Cuba by using this piece of equipment were presented. Seven patients had metastasis and one hepatocarcinoma. Two standard and 6 atypical resections were performed with no complications and just one patient needing blood transfusion.