BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. MATERIALS AND METHODS: HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. RESULTS: Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N⁵-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). CONCLUSION: Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.
Angiotensin II ; Animals ; Collagen ; Creatine Kinase ; Diet, High-Fat ; Glutathione ; Heart ; Heart Ventricles ; Hemodynamics ; Hypercholesterolemia ; Ischemia ; Ischemic Postconditioning ; L-Lactate Dehydrogenase ; Myocardial Infarction ; Myocardial Ischemia ; Nitric Oxide Synthase Type III ; Rats ; Reperfusion ; Reperfusion Injury ; Superoxides ; Troponin I ; Tumor Necrosis Factor-alpha

PURPOSE: The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef. RESULTS: ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/beta-catenin signaling pathway. CONCLUSION: Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/beta-catenin pathway to induce EMT in NPC.
Blotting, Western ; Carcinogenesis* ; Cell Line ; Clone Cells ; Epithelial-Mesenchymal Transition* ; Epithelium ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Heterografts ; Luciferases ; Microarray Analysis ; Oncogenes ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Small Interfering ; Wnt Signaling Pathway* ; Wound Healing ; Zidovudine ; Zinc Fingers

OBJECTIVE: To explore the association between the blood oxygenation T₂* values of resectable esophageal squamous cell carcinomas (ESCCs) and tumor stages. MATERIALS AND METHODS: This study included 48 ESCC patients and 20 healthy participants who had undergone esophageal T₂*-weighted imaging to obtain T₂* values of the tumors and normal esophagi. ESCC patients underwent surgical resections less than one week after imaging. Statistical analyses were performed to identify the association between T₂* values of ESCCs and tumor stages. RESULTS: One-way ANOVA and Student-Newman-Keuls tests revealed that the T₂* value could differentiate stage T1 ESCCs (17.7 ± 3.3 ms) from stage T2 and T3 tumors (24.6 ± 2.7 ms and 27.8 ± 5.6 ms, respectively; all p(s) < 0.001). Receiver operating curve (ROC) analysis showed the suitable cutoff T₂* value of 21.3 ms for either differentiation. The former statistical tests demonstrated that the T₂* value could not differentiate between stages T2 and T3 (24.6 ± 2.7 ms vs. 27.8 ± 5.6 ms, respectively, p > 0.05) or between N stages (N1 vs. N2 vs. N3: 24.7 ± 6.9 ms vs. 25.4 ± 4.5 ms vs. 26.8 ± 3.9 ms, respectively; all p(s) > 0.05). The former tests illustrated that the T₂* value could differentiate anatomic stages I and II (18.8 ± 4.8 ms and 26.9 ± 5.9 ms, respectively) or stages I and III (27.3 ± 3.6 ms). ROC analysis depicted the same cutoff T₂* value of 21.3 ms for either differentiation. In addition, the Student's t test revealed that the T₂* value could determine grouped T stages (T0 vs. T1–3: 17.0 ± 2.9 ms vs. 25.2 ± 6.2 ms; T0–1 vs. T2–3: 17.3 ± 3.0 ms vs. 27.1 ± 5.3 ms; and T0–2 vs. T3: 18.8 ± 4.2 ms vs. 27.8 ± 5.6 ms, all p(s) < 0.001). ROC analysis indicated that the T₂* value could detect ESCCs (cutoff, 20 ms), and discriminate between stages T0–1 and T2–3 (cutoff, 21.3 ms) and between T0–2 and T3 (cutoff, 20.4 ms). CONCLUSION: The T₂* value can be an additional quantitative indicator for detecting ESCC except for stage T1 cancer, and can preoperatively discriminate between some T stages and between anatomic stages of this tumor.
Carcinoma, Squamous Cell* ; Epithelial Cells* ; Esophagus ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging* ; Oxygen* ; ROC Curve