PubMed | Liaocheng Peoples Hospital, Charles Sturt University, Liaocheng University and Oral Maxillofacial Head Neck Key Laboratory of Medical Biology and Central Laboratory of Liaocheng Peoples Hospital
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016
Proteasome inhibitor Carbobenzoxy-Leu-Leu-leucinal (MG132) induces the unfolded protein response (UPR) in oral squamous cell carcinoma (OSCC). X-box binding protein 1 (XBP1) is a key UPR component that regulates endoplasmic reticulum stress (ER) homeostasis. This study was aimed to investigate the activation of IRE1-TRAF2-ASK1-JNK pathway by silencing the XBP1 expression in an OSCC cell line.The XBP1 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the Tca-8113 cells. The effect of XBP-1 gene silencing on IRE1-TRAF2-ASK1-JNK pathway under MG132 induced endoplasmic reticulum stress in Tca-8113 were investigated by real-time RT-PCR or western blot. Cell apoptosis was detected by flow cytometry.XBP1 expression was reduced in transfected groups and MG132 groups. shRNA-XBP1 induces IRE1-TRAF2-ASK1 signaling activation to activate pro-apoptotic ASK1-JNK signaling. Moreover, combined shRNA-XBP1 with MG132 further enhanced downregulated XBP1 expression and upregulated activation of ASK1-JNK signaling.Silencing XBP1 expression under MG132 induced ER stress block the XBP1 survival pathway and synergism with MG132 to promote Tca8113 cell apoptosis. These findings provide a therapeutic option in oral squamous cell carcinoma by inhibition of proteasome and XBP1 splicing.
PubMed | Shandong University and Oral Maxillofacial Head Neck Key Laboratory of Medical Biology and Central Laboratory of Liaocheng Peoples Hospital
Type: | Journal: Medical science monitor : international medical journal of experimental and clinical research | Year: 2015
Type 2 Diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease (CVD). Previous studies explored the association of T2DM with arterial stiffness and thickness biomarkers including the augmentation index (AIX), aortic pulse wave velocity (aPWV), brachial-ankle PWV (baPWV), carotid intima-media wall thickness (IMT) as well as blood pressure (BP), low density lipoprotein cholesterol (LDL-C); however the conclusions are either inconsistent or incomprehensive.The average differences of each included trial were expressed as the standardized mean difference (SMD) with 95% confidence interval (CI). Analyses of carotid IMT, aPWV, baPWV and AIX Systolic BP (SBP), diastolic BP (DBP), LDL-C and HDL-C were independently performed. Furthermore, subgroup analyses by ethnicity (Caucasian or Asian) were conducted. Beggs and Eggers tests were performed for potential publication biases detection.A total of 14 case-control eligible studies with 1222 T2DM patients and 1094 control subjects were included. In the overall analysis, significant associations were observed between the carotid IMT, aPWV, baPWV, LDL-C, HDL-C, SBP, and DBP with T2DM (IMT: p=1.1*10-12; aPWV: p=1.1*10-7; baPWV: p=1.8*10-33; LDL-C: p=3.1*10-8; HDL-C: p=6.1*10-18; SBP: p=3.9*10-21; DBP: p=4.8*10-5). No association was detected for AIX (p=0.09). Subgroup analyses indicated that aPWV, baPWV, SBP, LDL-C, and HDL-C were associated with T2DM in both white and Asian populations (p<0.05). The significant associations of IMT, AIX and DBP with T2DM were only observed in the Asian subgroup.Carotid IMT, aPWV, baPWV, as well as LDL-C, HDL-C, SBP, and DBP but not AIX were useful noninvasive early markers for T2DM vascular dysfunction detection.