Design, Synthesis, and Activity Evaluation of Novel Acyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro, of which 3-(6-chloro-9H-purin-9-yl)dodecan-1-ol (9b) exhibited the most potent effect against the HCT-116 and SW480 cells with IC50 values of 0.89 and 1.15 µM, respectively. Furthermore, all of the (R)-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their (S)-counterparts. Mechanistic studies revealed that compound 9b triggered apoptosis in the cancer cell lines via depolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9b inhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9b may serve as a promising lead compound that merits further attention in future anticancer drug discovery.

Blood lipid profiles and factors associated with dyslipidemia assessed by a point-of-care testing device in an outpatient setting: A large-scale cross-sectional study in Southern China.

OBJECTIVE: To promote the concept of POCT and to investigate dyslipidemia in Guangzhou, China, we performed a study examining blood lipids assessed by POCT and reported factors associated with dyslipidemia. DESIGN AND METHODS: This multicenter, cross-sectional study enrolled outpatients from 9 Guangzhou hospitals from May through September 2013. After informed consent was obtained, the following information was collected: age; gender; the presence of diabetes mellitus, obesity, and hypertension as well as current use of cigarettes or alcohol. Patients were asked to fast for 8h before the blood examination performed on a POCT device, the CardioChek PA. RESULTS: Of 4012 patients enrolled (1544 males, 2468 females; mean age 60.35±9.41 years), 1993 (49.7%) patients had dyslipidemia, but only 101 (5.1%) took statins. The multivariate tests of associations between demographic variables, comorbidities, and the risk of having dyslipidemia found that the significant predictors of dyslipidemia were male gender, age ≥60 years, being a current smoker or alcohol drinker, and hypertension. CONCLUSION: Most dyslipidemia patients in Guangzhou remain untreated. POCT in China is feasible, and its widespread use might improve dyslipidemia awareness, treatment and control.

[Effect of percutaneous intervention on adrenomedullin and tumor necrosis factor in the coronary circulation].

OBJECTIVE: To evaluate the effect of percutaneous intervention (PCI) on coronary circulation levels of adrenomedullin (ADM) and tumor necrosis factor alpha (TNF-alpha) in patients with coronary heart disease (CHD). METHODS: Thirty-three CHD patients underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting (altogether 48 stents were implanted). Blood samples were collected from the coronary sinus and femoral artery at the time points of immediately before and after angioplasty, immediately after PTCA or stenting, 10 min after procedures, respectively. RESULTS: The ADM and TNF-alpha levels in the coronary sinus varied little after coronary angiography, but were elevated markedly following PTCA from the basal levels of 36.3+/-1.3 pg/ml to 28.9+/-1.9 pg/ml (P<0.01) and from 11.10+/-0.46 ng/ml to 8.84+/-0.37 ng/ml (P<0.01), respectively. Further increases of ADM and TNF-alpha levels were detected immediately after stent deployment. ADM recovered to basal levels 10 min after completion of the procedures, while TNF-alpha underwent further increase. Before the procedure, ADM and TNF-alpha levels were higher in the coronary sinus than in the femoral artery (28.9+/-1.9 pg/ml vs 22.6+/-0.8 pg/ml, P<0.01; 8.84+/-0.37 ng/ml vs 7. 56+/-0.23 ng/ml, P<0.01, respectively), and their levels in the femoral artery did not undergo significant changes in response to the operations. CONCLUSION: The coronary circulation levels of ADM and TNF-alpha increase after PTCA and stenting but not after coronary angiography in CHD patients, which might be attributed to injuries by the procedures as well as the mechanical stimulation by the stent.

[Relation of the ST-segment elevation pattern in acute phase of anterior wall acute myocardial infarction to short-term prognosis].

OBJECTIVE: To observe the relation of ST-segment elevation pattern of electrocardiogram (ECG) recorded in acute phase of anterior wall acute myocardial infarction (AMI) to short-term prognosis. METHODS: Sixty-two patients with first anterior wall AMI were divided into 3 groups according to ST-segment elevation pattern in lead V3 of a 12-lead ECG at admission. Patients in group A (n=18) were characterized by concave type of ST-segment elevation, group B (n=27) by straight type and group C (n=17) by convex type. The peak value of serum creatine phosphate kinase (CPK) and left ventricular ejection fraction (LVEF) were measured. The incidence of serious complications (including malignant arrhythmia, left ventricular dysfunction and cardiogenic shock) and mortality within the initial 4 weeks of hospitalization were recorded. RESULTS: The median value of peak CPK of the 3 groups was 2 014.4, 4 486.8 and 5 826.9 IU/L respectively, and the peak value of CPK in group A was much lower than that in groups B and C ( D<0.05 and P<0.01, respectively). LVEF measured by echocardiogram within 14 d after myocardial infarction were 61.2%, 48.6% and 38.7% respectively, showing significant difference between groups A and B and between groups B and C (P<0.05) as well as between group A and C (P<0.01). The incidences of serious complications and mortality within 4 weeks after AMI in group A were much lower than those in groups B and C (P<0.05), but there was no significant difference between groups B and C ( D>0.05). CONCLUSION: The shape of ST-segment elevation in lead V3 of a 12-lead ECG in acute phase of anterior wall AMI may reflect the severity of myocardial ischemic injury, and convex type of ST-segment elevation in lead V3 in acute phase often indicate poor short-term prognosis.