精神分裂症患者血浆MicroRNA异常表达的对照研究

目的检测microRNA（miRNA或miR）在精神分裂症患者中的异常表达,探究miRNA能否作为精神分裂症的生物标记物。方法连续入组64例精神分裂症患者和64例配对正常对照,使用实时荧光定量RT—PCR技术检测病例组和对照组血浆10种miRNA（miR-30e、miR一34a、miR一181b、miR一195、miR一346、miR一432、miR一7、miR一132、miR一137andmiR一212）的相对表达水平。结果病例组血浆miR一30e、miR一18lb、miR一346、miR一34a和miR一7表达水平（2．99±1．59,2．29±0．77,4．24±1．51,9．94±1．52,11．08±2．24）较对照组（3．74±1．28,2．87±0．90,4．65±0．99,10．90±1．99,12．00±1．95）显著上调（P〈0．05—0．001）。ROC曲线分析显示,5种miRNA作为联合生物标记物对精神分裂症具有较高诊断价值（AUC为0．705,敏感度和特异度分别为34．5％和90．2％）;Logistic回归分析显示miR-181b具有最高相对危险度（OR=2．483）。结论miR一30e、miR一181b、miR一346、miR一34a和miR．7可能成为精神分裂症的联合生物标记物。     

Discovery of the cancer stem cell related determinants of radioresistance

Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies.     

Combination of p53(ser15) and p21/p21(thr145) in peripheral blood lymphocytes as potential Alzheimer's disease biomarkers

Alzheimer's disease (AD) is still difficult to be precisely diagnosed in its early stage to date. Establishing of reliable and manageable disease-specific biological markers is required to improve diagnostic accuracy. Based on the hypothesis of cell cycle regulatory failure at the early stage of AD, we tested whether cell cycle regulating proteins p53, p21 and their phosphorylated forms p53(ser15), p21(thr145) were changed in AD patients and whether these proteins could be used as diagnostic biomarkers. Western bolt, Enzyme-linked immunosorbent assay (ELISA), immunofluorescent staining and flow cytometry (FCM) analysis were employed to analyze levels of these proteins in peripheral blood lymphocytes (PBLs) from 95 controls, 94 AD, 12 Parkinson's disease (PD) and 15 vascular dementia (VaD) patients. Compared with controls, p53(ser15) and p21(thr145) levels were significantly increased and p21 level was significantly decreased in PBLs of AD patients but not in PD or VaD, while p53 was increased in both AD and VaD patients. The receiver operating characteristic (ROC) curve analysis showed that the specificity and sensitivity were 76% and 84% for p53, 88% and 82% for p53(ser15), 80% and 75% for p21 and 84% and 68% for p21(thr145) in identifying AD patients. The relatively high diagnostic accuracy support these proteins, especially p53(ser15) and p21 in PBLs may become potential biomarkers for diagnosis of AD.     

Cyclooxygenase-2 -765G>C polymorphism is associated with C-reactive protein levels in resistant smokers but not in chronic obstructive pulmonary disease patients

We sought to investigate whether the serum concentrations of several inflammatory biomarkers are related to the cyclooxygenase-2 (COX2) −765G>C polymorphism in chronic obstructive pulmonary disease (COPD) and a control group of non-COPD smokers. Serum inflammatory markers (CRP, SAA, CXCL8, and sICAM-1) were measured by ELISA in 144 patients with COPD and in 55 control subjects. Genomic DNA was extracted from peripheral blood leukocytes, and the COX2 −765G>C (rs20417) polymorphism was genotyped. After adjustment for age and active smoking, CRP and SAA concentrations were associated with the COX2 polymorphism in controls (p = 0.041 and 0.014, respectively) but not in COPD patients. The CXCL8 and sICAM-1 concentrations were not associated with the COX2 polymorphism for either cases or controls. The results of the present study indicate that there is a relationship between the COX2 −765G>C polymorphism and the concentrations of CRP and SAA in non-COPD smokers and that this relationship does not exist in COPD patients.     

Early prediction of acute kidney injury in patients with acute myocardial injury

Introduction

Previous studies have revealed that acute myocardial infarction (AMI) with acute kidney injury (AKI), about 17%, is strongly related to long-term mortality and heart failure. The dynamic changes in renal function during AMI are strongly related to long-term mortality and heart failure.

Objectives

Our study used clinical parameters and AKI biomarkers including neutrophil gelatinase–associated lipocalin, interleukin (IL)-6, IL-18, and cystatin C to evaluate prognostic relevance of AKI in the setting of AMI.

Methods

This prospective study was conducted from November 2009 to January 2011 and enrolled sequential 96 patients with catheter-proven AMI; it was approved by the institutional review board of Chang Gung Memorial Hospital, Taiwan (institutional review board no. 99-0140B) and conformed to the tenets of the Declaration of Helsinki. The definition of AKI is the elevation of serum creatinine of more than 0.3 mg/dL within 48 hours.

Results

Our results show that the incidence of AKI after AMI is 17.7% (17 patients). The following could be statistically related to AKI after AMI: age (P = .012), cardiac functions (Killip stage and echocardiogram; P = .003 each), Thrombolysis in Myocardial Infarction (TIMI) flow grade (P < .001), stenting (P < .001), neutrophil gelatinase–associated lipocalin (P = .005), IL-6 (P = .01), IL-18 (P = .002), and cystatin C (P = .002) in serum. The TIMI flow grade and serum cystatin C were shown to be important predictors by using multivariate analysis. Both TIMI flow lower than grade 2 and serum cystatin C of more than 1364 mg/L could be used to predict AKI (both overall correctness, 0.78). Moreover, IL-6 in serum is also associated with the major cardiovascular events after AMI (P = .02), as demonstrated in our study.

Conclusion

In conclusion, the worse TIMI flow and high plasma cystatin C can be used to predict AKI after AMI. Moreover, IL-6 can also be used as a 30-day major cardiovascular event indicator after AMI. A larger prospective and longitudinal study should follow the relationship between AKI predictors after AMI.     

Preeclampsia from a renal point of view: Insides into disease models,biomarkers and therapy

Proteinuria is a frequently detected symptom, found in 20% of pregnancies. A common reason for proteinuria in pregnancy is preeclampsia. To diagnose preeclampsia clinically and to get new insights into the pathophysiology of the disease it is at first essential to be familiar with conditions in normal pregnancy. Animal models and biomarkers can help to learn more about disease conditions and to find new treatment strategies. In this article we review the changes in kidney function during normal pregnancy and the differential diagnosis of proteinuria in pregnancy. We summarize different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. We describe the current animal models and give a broad overview of different biomarkers that were reported to predict preeclampsia or have a prognostic value in preeclampsia cases. We end with a summary of treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia. Most of these novel biomarkers for preeclampsia are not yet implemented in clinical use. Therefore, we recommend using proteinuria (measured by UPC ratio) as a screening parameter for preeclampsia. Delivery is the only curative treatment for preeclampsia. In early preeclampsia the primary therapy goal is to prolong pregnancy until a state were the child has an acceptable chance of survival after delivery.