PubMed | Jinling Hospital Nanjing and People's Care
Type: Journal Article | Journal: International journal of clinical and experimental medicine | Year: 2016
Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 M DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway.
PubMed | Jinling Hospital Nanjing, Yongchuan Hospital of Chongqing Medical UniversityChongqing, Hospital of Traditional Chinese Medicine Chongqing and Qingdao University
Type: | Journal: Frontiers in pharmacology | Year: 2016
Hydrogen is a proven novel antioxidant that selectively reduces hydroxyl radicals. In this study, we investigated the effects of hydrogen-rich saline solution on the prevention of renal injury induced by ischemia/reperfusion (I/R) and on renal function recovery.A rat model of renal I/R injury was induced by 45 min occlusion of the left renal pedicle, followed by 108 h reperfusion. The right kidney was surgically removed. Then, 0.9% NaCl solution (1 ml/kg) or hydrogen-rich saline solution (HRSS; 1 ml/kg) was injected into the abdominal cavity at 4 h intervals. We assessed the influence of HRSS or control saline solution on the recovery of renal function after I/R injury. Kidney tissues were taken at different time points (24, 36, 48, 72, and 108 h after reperfusion) and frozen (-80C). Kidney cell apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive staining. Additionally, the apoptotic factors (Bcl-2, Bax, caspase-3, caspase-9, and caspase-8) and the pro-inflammatory cytokines (IL-6 and TNF-) were measured in the kidney tissues. Finally, serum blood urea nitrogen (BUN) and creatinine (Cr) levels were measured.Histological analyses revealed a marked reduction of interstitial congestion, edema and hemorrhage in renal tissue after HRSS treatment compared to saline treatment. After I/R injury, BUN, Cr, Bcl-2, caspase-3, caspase-9, caspase-8, IL-6, and TNF- were all significantly increased, while Bax expression was decreased. HRSS remarkably reversed these changes. Moreover, BUN and Cr decreased more rapidly in the rats treated with HRSS compared to the rats treated with control saline solution.HRSS showed a protective effect in the prevention of renal injury and could promote renal function recovery after I/R injury in rats. HRSS might partially exert its role through an anti-apoptotic and anti-inflammatory action in kidney cells.
PubMed | Nanjing Medical University, Jiangsu Province Geriatric Hospital Nanjing and Jinling Hospital Nanjing
Type: Journal Article | Journal: International journal of clinical and experimental pathology | Year: 2015
EphB6 is a member in the receptor tyrosine kinase Eph family in that its kinase domain contains several alterations in conserved amino acids and is catalytically inactive. Although EphB6 is expressed both in a variety of embryonic and adult tissues, biological functions of this receptor are largely unknown. In this study, we examined the expression of EphB6 protein in 54 of tissue specimens of tongue squamous cell carcinoma by using a specific polyclonal anti-EphB6 antibody. The relationship between expression of EphB6 and clinical pathologic parameters was analyzed. The expression level of EphB6 in carcinoma cells from 34 out of 54 (63%) specimens was no alterative compared with normal squamous cells in same patient. The level of EphB6 protein staining was increased in carcinoma cells in 20 out of 54 (37%) specimens compared with normal squamous cells in same patient. The high-expression of EphB6 was significantly associated with age (P=0.021), tumor TNM stage (P=0.026) and lymph node metastasis (P=0.046). Patients with high expressed EphB6 protein had a high mortality (P=0.057). No significant relationship between expression of EphB6 and sex, tumor grade, HPV infection, relapse and smoke was found. We showed that patients with high expression of EphB6 had a significantly poor overall survival (OS) compared to patients with negative or weak expression (P=0.042). Our results indicated that EphB6 protein may be used as a new marker for prognosis for tongue squamous cell carcinoma.