Objectives. This study aims to investigate the effect of betulinic acid (BA) on myocardial ischemia reperfusion/injury in an open-chest anesthetized rat model. Methods. The model was induced by 30 minutes left anterior descending occlusion followed by 2 hours reperfusion. There are six groups in our present study: sham operation group, ischemia/reperfusion group, low-dosage BA group, medium-dosage BA group, high-dosage BA group, and fosinopril sodium group. Rats in the latter four groups were administrated with BA (50, 100, and 200 mg/kg, i.g.) or fosinopril sodium (10 mg/kg, i.g.) once a day for 7 days before operation, respectively. Rats in the former two groups were given the same volume of vehicle (0.5% CMC-Na, i.g.). During the operation, cardiac function was continuously monitored. Serum LDH and CK were measured with colorimetric assays. The expression of Bcl-2 and Bax and the apoptosis of cardiomyocytes were investigated with western blot and TUNEL assay, respectively. Results. Pretreatment with BA improved cardiac function and attenuated LDH and CK activities compared with IR group. Further investigation demonstrated that the expression of Bcl-2 and Bax and TUNEL assay was in line with the above results. Conclusion. BA may reduce the release of LDH and CK, prevent cardiomyocytes apoptosis, and eventually alleviate the extent of the myocardial ischemia/reperfusion injury.
Cisplatin (DDP) has been successfully used in the treatment of gastric cancer; however, resistance of gastric tumors to cisplatin has also resulted in frequent treatment failure. To investigate the effect of sorafenib in reversing the resistance of human gastric cancer cell line SGC7901/DDP to treatment by cisplatin, and to examine possible underlying mechanisms. A SGC7901/DDP cell line was treated with different concentrations of sorafenib, with and without cisplatin. The reversing ability of sorafenib on cisplatin treatment was examined using MTT, FACS, and xenograft models. Western blotting and immunofluorescence were used to determine expressions of MDR1, p-Akt, and p-ERK. Sorafenib inhibited proliferation of human gastric cancer cell line SGC7901/DDP, both when used alone and in combination with cisplatin. Expression levels of MDR1, p-Akt, and p-ERK were significantly decreased after sorafenib treatment. Sorafenib may reverse resistance of human gastric cancer cell line SGC7901/DDP to cisplatin through down-regulating MDR1 expression.
Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.
To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p< 0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p< 0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.
Taken together, it is suggested that the renal protective effect may be related to the levels of HSP27 and MAPKAPK-2 activation.
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