Inhibition of Aß peptide aggregation by ruthenium(II) polypyridyl complexes through copper chelation.

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid ß peptide (Aß) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu2+ from Aß and become dimers upon Cu2+ coordination and show high efficiency for both Cu2+ elimination and Aß assembly inhibition. Besides, these designed complexes can inhibit the production of Aß-induced reactive oxygen species (ROS), protect mitochondria from damage, and improve the survival rate of neuron cells. Our work provides a new strategy to combine hydrophobic interaction and metal ion chelation to design amyloid inhibitors.

Mitochondria-targeted cyclometalated rhodium(III) complexes: synthesis, characterization and anticancer research.

Over the past few decades, the landscape of inorganic medicinal chemistry has been dominated by investigations on platinum or ruthenium, while the research based on other metal centers such as rhodium has been relatively insufficient. In this work, a series of cyclometalated rhodium(iii) complexes with imidazo[4,5-f][1,10]phenanthroline containing different aromatic rings were synthesized and characterized. Notably, all the complexes displayed stronger anticancer activity against various cancer cells compared with cisplatin. A mechanism study revealed that the rhodium complexes accumulated in the mitochondria, elevated the levels of mitochondrial reactive oxygen species (ROS) and released cytochrome c, indicating severe mitochondrial damage during the anticancer activity. Further studies illustrated that the rhodium complexes caused cell cycle arrest at the G2/M phase, upregulated the expression of p53 and reduced the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated x (Bax), which ultimately resulted in cellular apoptosis. Overall, through mitochondrial pathways, these Rh(iii) complexes could induce cellular apoptosis to a larger extent than cisplatin and should be paid close attention as promising chemotherapeutic drugs in anticancer research.

Mitochondrial targeted rhodium(III) complexes: Synthesis, characterized and antitumor mechanism investigation.

Recently, rhodium complexes have received intensive attentions due to their tunable chemical and biological properties as well as attractive antitumor activity. In this work, two imidazole triphenylamino rhodium complexes [Rh(ppy)2L1]PF6 (Rh1) and [Rh(ppy)2L2]PF6 (Rh2) (ppy = 2-phenylpyridine, L1 = 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline, L2 = N-(4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl)-4-methyl-N-(p-tolyl)aniline) have been synthesized and characterized. Both complexes display stronger anticancer activity against a various of cancer cells than cisplatin and they can effectively localize to mitochondria. Further mechanism studies show that Rh1 induce caspase-dependent apoptosis through mitochondrial damage, down-regulate the expression of B-cell lymphoma-2 (Bcl-2)/Bcl2-associated x (Bax) and reactive oxygen species (ROS) elevation. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of rhodium complexes.

Value of the Barthel scale in prognostic prediction for patients with cerebral infarction.

BACKGROUND: This study aims to evaluate the ADL(activity of daily living) of patients with acute cerebral infarction through BI scoring, in order to observe its predictive value in the prognosis of these patients. METHODS: According to the inclusion and exclusion criteria, patients with acute anterior circulation cerebral infarction were included in the present study. Then, the BI scoring was analyzed through five grades, in order to further investigate the dose-response relationship between BI scoring and mortality risk in patients with cerebral infarction. The receiver operating characteristic (ROC) curves for BI-scored patients were drawn, and the predictive authenticity of the Barthel scale in prognostic prediction for patients with cerebral infarction was estimated. RESULTS: The difference in BI scores between the survival group and death group were statistically significant (t = 10.029, P < 0.05), in which the score was lower in the death group than in the survival group. According to the linear trend ×2-test, the decrease in BI score indicates an increase in mortality risk in patients with cerebral infarction. The area under the curve (AUC) of the ROC curve was 0.794 with a P-value of < 0.05. CONCLUSION: BI scoring is a highly valuable scoring system for the prognostic prediction of patients with acute cerebral infarction.

A Prospective Study of Comparing the Application of Two Generation Scoring Systems in Patients with Acute Cerebral Infarction.

INTRODUCTION: This study aims to compare the value of acute physiologic and chronic health evaluation scoring systems (APACHE II and APACHE III) among patients with acute cerebral infarction. METHODS: The APACHE II and APACHE III scores were determined in 399 patients with acute cerebral infarction within 24 h of admission in order to investigate their predictive value for prognosis in acute cerebral infarction. The area under the ROC curve was used to measure the ability of two scoring systems in predicting the prognosis of patients, and the area under the curve of the two scoring systems was compared. RESULTS: The APACHE II and APACHE III scoring systems demonstrated good predictive value for prognosis in acute cerebral infarction, and the areas under the receiver operating characteristic were 0.808 and 0.818, respectively. There was no significant difference in the area under the curve between these two scoring systems. CONCLUSION: Both the APACHE II and APACHE III scoring systems had good predictive value for prognosis in acute cerebral infarction, and there was no obvious difference between these two systems. Preference was suggested for APACHE II.

Predictive values of CSS and NIHSS in the prognosis of patients with acute cerebral infarction: A comparative analysis.

This study aims to investigate the predictive values of the Chinese Stroke Scale (CSS) and National Institutes of Health Stroke Scale (NIHSS) in the prognosis of patients with acute cerebral infarction.A total of 399 patients with acute cerebral infarction were assessed using CSS and NIHSS within 1 day after admission. Then, the receiver operating characteristic (ROC) curves were established, and the area under the curves of these 2 scoring systems was compared.The area under the curve of CSS and NIHSS was 0.796 and 0.794, respectively.CSS and NIHSS have good predictive values for the prognosis of patients with acute cerebral infarction.

[Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model].

OBJECTIVE: To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. METHODS: We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. RESULTS: During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X1) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X2) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X3) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X4) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X5) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X6) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X1 + 0.681X2 + 0.973X3 + 0.395X4 + 0.283X5 + 0.636X6. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. CONCLUSION: Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed.