Camptothecin inhibits the progression of NPC by regulating TGF-ß-induced activation of the PI3K/AKT signaling pathway.

Nasopharyngeal carcinoma (NPC) is a type of cancer that is characterized by increased invasiveness, metastatic potential and tumor recurrence. Camptothecin has been demonstrated to exhibit anticancer activity. However, the potential underlying molecular mechanisms mediated by camptothecin in NPC cells remain elusive. In the present study, the efficacy of camptothecin for NPC was investigated in vitro and in vivo. Additionally, the potential signaling pathway mediated by camptothecin in NPC cells was also examined. The results indicated that the viability and aggressiveness of NPC cells were suppressed by camptothecin treatment in a dose-dependent manner. Camptothecin administration downregulated the expression levels of cell-cycle-associated proteins including cyclin 1, cyclin-dependent kinase (CDK)1 and CDK2 in NPC cells. Expression levels of migration-associated proteins including vimentin, fibronectin and epithelial cadherin were regulated by camptothecin treatment in NPC cells. Additionally, camptothecin inhibited the expression of transforming growth factor-ß (TGF-ß), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), whereas TGF-ß overexpression abrogated camptothecin-mediated inhibition of PI3K and AKT expression and camptothecin-mediated inhibition of the viability and aggressiveness of NPC cells. Camptothecin significantly inhibited tumor growth and increased survival times in a mouse model of cancer. In conclusion, these results indicate that camptothecin treatment may inhibit the viability of NPC cells and aggressiveness by regulating the TGF-ß-induced PI3K/AKT signaling pathways, which in turn may be a potential molecular target for the treatment of NPC.

Anti-neutrophil cytoplasmic antibodies in cholesterol embolism: A case report and literature review.

Cholesterol embolism is a multisystemic disorder with clinical manifestations that resemble vasculitis. Anti-neutrophil cytoplasmic antibodies (ANCA) are a defining feature of ANCA-associated vasculitis, and the presence of ANCA in cholesterol embolism complicates its differential diagnosis and treatment. At present, the role of ANCA in cholesterol embolism remains unclear and no effective treatment is currently available. The present study reports the case of an Asian male who presented with spontaneous cholesterol embolism with proteinase 3 (PR3)-specific ANCA, subacute interstitial nephritis and late-developing skin lesions. The 69-year-old patient was admitted to The First Affiliated Hospital of Xiamen University (Xiamen, China) complaining of chest tightness, fatigue, progressive renal failure and refractory hypertension. In addition, transient eosinophilia was detected. Following immunosuppressive therapy with steroids and cyclophosphamide for 6 months, hemodialysis treatment was initiated. Skin lesions appeared at >1 month following hemodialysis initiation; however, they were gradually improved following treatment with atorvastatin and anti-platelet aggregation therapy for 5 months. The patient was maintained on hemodialysis for ~2 years and exhibited general good health at the most recent follow-up. In addition, 11 cases of cholesterol embolism associated with ANCA reported in the literature were discussed in the present study.

KLF15 suppresses cell proliferation and extracellular matrix expression in mesangial cells under high glucose.

Excess mesangial extracellular matrix (ECM) and mesangial cell (MC) proliferation is the major pathologic feature of diabetic nephropathy. Kruppel-like factor 15 (KLF15) is a member of the KLF transcription factor family that plays a critical role in regulating renal fibrosis. However, the role of KLF15 in diabetic nephropathy remains poorly understood. This study was conducted to explore the role of KLF15 in the development and progress of diabetic nephropathy in high glucose (HG)-stimulated human MCs. Here, we found down-regulated expression of KLF15 in MCs induced by HG. Overexpression of KLF15 significantly inhibited MCs proliferation and ECM production induced by HG. Moreover, overexpression of KLF15 inhibited HG-induced ERK1/2 phosphorylation in MCs. In summary, our data demonstrate that KLF15 can suppress HG-induced cell proliferation and ECM protein fibronectin expression in human MCs via ERK1/2 MAPK signaling. The results provide evidence that KLF15 might be a potential molecular target for the treatment of diabetic nephropathy.

[Effect of nasal cavity expansion surgery on chronic nasal obstructive diseases on the blood supply of the cerebral arterial system].

OBJECTIVE: To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system. METHODS: Fifty-nine inpatients with abnormal blood supply of cerebral arterial system confirmed by transcranial doppler (TCD) and chronic nasal obstructive diseases were included in this study. All patients accepted nasal cavity expansion surgery and were followed-up with TCD every month after operation until TCD became normal, or up to seven months even if the TCD was still abnormal. SPSS 17.0 software was used to analyze the data. RESULTS: In all 59 patients, there were 164 TCD-abnormal cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries became normal within 1 to 7 months after operation, 8 patients (13.56 %) got better, but 14 patients (23.73 %) did not improve. CONCLUSIONS: Abnormal blood flow of some cerebral arteries was possibly induced by increasing the activation of sympathetic nervous system around the vertebral arterial system, caused by chronic nasal obstruction. Nasal dilatancy surgery can improve the blood supplement of the cerebral arterial system.

[Clinical significance of D-dimer activity in thrombosis of patients with return of spontaneous circulation after cardiopulmonary resuscitation].

OBJECTIVE: To investigate the clinical significance of D-dimer contents in peripheral blood for monitoring the efficacy of thrombolytic therapy in patients with return of spontaneous circulation (ROSC) of cardiopulmonary resuscitation (CPR) cardiopulmonary resuscitation after cardiac arrest. METHODS: Forty-seven patients with sudden cardiac arrest received CPR according to 2005 American Heart Association (AHA) guidelines for CPR and emergency cardiovascular care (ECC). At the early stage of ROSC, those patients underwent head and breast CT scan if they were in a state of unconsciousness and had unstable vital signs. If intracranial hemorrhage, dissection of aorta and pneumothorax were rule out, and those patients who maintained blood circulation for over 24 hours were included. The expression of D-dimer contents in peripheral blood was determined at 0, 1, 2, 4, 8, 12 h after CPR in all patients. And the patients were randomly divided into control and experiment groups. Prior to thrombolysis, the patients whose D-dimer more than 512 µg/L were classified as Group A (n = 17); those whose D-dimer below 512 µg/L Group B (n = 14); and the remaining control group whose family members refused thrombolytic therapy Group C (n = 16). The general data, Glasgow coma scale, survival rate and the change of D-dimer in peripheral blood were analyzed. RESULTS: In Group A, D-dimer level began to increase significantly at CPR 1 hour. It peaked at CPR 2 hours then decreased gradually. The final survival rate was 67%. The survival rate and GCS were higher than those of Groups B and C. In Group B, the D-dimer concentrations began to increase gradually at CPR1 hour, peaked at CPR 12 hours and then decreased. The survival rate and GCS was lower than those of Group A and similar to those of Group C. Group C was control group with no thrombolysis. CONCLUSION: For those ROSC patients with D-dimer concentrations significantly higher than usual, the pathogenesis of cardiac arrest may be concerned with thromboembolism, thrombosis in circulatory system and hyperviscosity. After an initiation of thrombolytic therapy, blocked blood vessels are recanalized, blood circulation improves and the cause of cardiac arrest is removed. Thus their survival rate becomes better. For those with D-dimer concentrations no higher than usual, the cause of cardiac arrest is not concerned with thromboembolism, thrombolytic therapy can not improve the patient outcome. And the final survival rate remains unchanged. The significance of thrombolytic therapy is none.

[Identification and diagnosis of myocardial damage and acute myocardial infarction during cardiopulmonary resuscitation].

OBJECTIVE: To observe the change in contents of creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI) in peripheral blood, the elevation of ST in electrocardiogram, and the result of coronary arteriography, to identify myocardial damage and acute myocardial infarction during cardiopulmonary resuscitation (CPR). METHODS: Twenty-six patients with sudden cardiac arrest received CPR, and those patients who had blood circulation maintained for over 24 hours were included. The expression of CK-MB and cTnI activation in peripheral blood were determined at 0, 4, 8, 12, 16 and 20 hours after CPR in all patients. Electrocardiogram was checked every 2 hours in all patients. If CK-MB, cTnI and ST segment of electrocardiogram was higher than usual, or myocardial infarct with suspicious elevation of ST (STEMI), coronary arteriography and interventional therapy were carried out immediately. Patients were divided into three groups. The patients who were not found to have coronary artery block were classified as group A (15 cases), those who were found to have coronary artery block were group B (6 cases), and the remaining patients in whom ST segment of electrocardiogram did not elevate, and coronary arteriography and interventional therapy were not consider were classified as group C (5 cases). Control group consisted of 15 healthy people (group D). The change in CK-MB and cTnI in peripheral blood and the elevation of electrocardiogram ST segment were analyzed. RESULTS: In group A, CK-MB level began to elevate at CPR 4 hours, and it peaked at CPR 12 hours. cTnI began to raise at CPR 4 hours, peaking at CPR 16 hours, then decreased gradually. Elevation of ST was seen in more than two leads in electrocardiogram at the beginning of restoration of spontaneous circulation (ROSC), then lowered quickly, and the decrease exceeded 50% of the elevation at ROSC 2 hours. In group B, the levels of CK-MB and cTnI began to increase at CPR 4 hours, and remained elevated at CPR 20 hours. ST segment was elevated in more than two leads in electrocardiogram at the beginning of ROSC, and remained elevated after ROSC 2 hours. In group C, the CK-MB and cTnI concentrations were increased 4 hours after successful CPR, and reached peak at CPR 12, 16 hours respectively, then they decreased. ST segment of electrocardiogram was not elevated. In group D, the CK-MB and cTnI concentration was in the normal range. ST segment of electrocardiogram was not elevated. CONCLUSION: All patients manifested myocardial damage after CPR. Some patients showed STEMI after CPR. CK-MB and cTnI concentrations increased gradually after successful CPR without specificity for earlier identification of myocardial damage and STEMI. It is necessary to find a new reliable marker to check for myocardial damage. Relatively speaking, elevation of the ST segment in electrocardiogram has more predictive value. A decrease exceeds 50% of the elevation of ST segment in electrocardiogram at ROSC 2 hours, or the peak of contents of CK-MB and cTnI appear at CPR 12 hours or 16 hours indicates myocardial damage. If the elevation of ST segment does not descend after ROSC 2 hours, or the levels of CK-MB and cTnI remain elevated at CPR 20 hours, STEMI should be suspected, and it is necessary to undertake interventional therapy or thrombolysis therapy.