The antimalarial activity of indole alkaloids and hybrids.

Malaria, caused by the genus Plasmodium, remains a global public health concern. It is estimated by the World Health Organization that over 40% of the world's population lives in areas at risk for malarial transmission, and around half a million people succumb to this infectious disease annually, which is related to the rapid spread of drug-resistant parasite strains. Indole derivatives, which possess broad-spectrum pharmacological properties, play a crucial role in the discovery of new drugs. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug-sensitive and drug-resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents. This review outlines the advances in indole alkaloids and hybrids with antimalarial potential in the recent decade.

[Genetic characteristics of HIV-1 primary drug resistance-associated mutations in treatment-naive individuals in Liaoning province, 2004-2008].

OBJECTIVE: To investigate the HIV-1 drug resistance associated mutations and examine the susceptibility of HIV-1 with these mutations to antiretroviral in treatment-naive individuals in Liaoning province from 2004 to 2008. METHODS: RNA was extracted from 20 plasma samples of diagnosed untreated HIV-1-infected treatment-naive patients by drawing method. After the viral loading (VL) test, the protease and nucleoside reverse transcriptase coding regions were amplified by RT-PCR, nested PCR and sequence analysis directly. Levels of resistance and prevalence were evaluated according to the Stanford University HIV Drug Resistance Database's algorithm (http://hivdb.stanford.edu). RESULTS: Among the 20 plasma samples, 13 got PCR products because of their VL values higher than 1000 copies/ml.Meanwhile, the 13 samples got 65 sequences by using 5 primers each. Polymorphisms in subtype H and circulating recombinant forms (CRFs) CRF10_CD sequences were identified. An overall prevalence of 30.8% (4/13) resistance to NNRTIs, 7.7% (1/13) to PI and no NRTIs mutations were found. The most frequent substitutions (4/13) in the RT region at positions P225H, K238S, V179D, K238T and a major position I54S in PR implied to a multiple drug-resistance. A71V or L10V only, respectively, substitution in PR was found in 3 samples, but no any worse with drug sensitivity. CONCLUSION: HIV-1 polymorphisms in subtype H and CRFs CRF10_CD sequences were identified circulating in Liaoning. A major mutation position I54S in PR implied that it would be the time to commence a higher level drug regimen.

Depletion of VAX2 Restrains the Malignant Progression of Papillary Thyroid Carcinoma by Modulating ERK Signaling Pathway.

OBJECTIVE: Ventral anterior homeobox 2 (VAX2) gene is a key regulating factor for the development of the ventral region of the eye, and has recently attracted much attention from the cancer treatment field. Our study aimed to explore the effect of VAX2 on papillary thyroid carcinoma (PTC). METHODS: We determined the expression levels of VAX2 in PTC based on The Cancer Genome Atlas (TCGA) database. We then assessed the prognosis of patients with PTC, and analyzed the association between VAX2 expression and clinicopathological characteristics. Subsequently, we measured the biological functions of VAX2 in PTC using qRT-PCR, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assays and western blot. RESULTS: VAX2 was up-regulated in PTC tissues when compared with normal thyroid tissues, and high expression level of VAX2 was positively correlated with poor prognosis. Furthermore, knockdown of VAX2 significantly inhibited the proliferation, migration and invasion of PTC cells. Importantly, through western blot analysis, we found that the expression of phosphorylated-(p) ERK and p-MEK in ERK signaling pathway showed a significant decrease after knockdown of VAX2. CONCLUSION: These findings suggest that VAX2 may be involved in the malignant progression of PTC, and hold significant potential as a therapeutic target for PTC.

Evaluation of left ventricular mechanical dyssynchrony in chronic heart failure patients by two-dimensional speckle tracking imaging.

The purpose of this study was to evaluate left ventricular mechanical dyssynchrony (LVMD) in chronic heart failure (CHF) patients using two-dimensional speckle tracking imaging (2D-STI), and also to compare the usefulness of three patterns of myocardial deformation in mechanical dyssynchrony assessment. Furthermore, the relationships between left ventricular ejection fraction (LVEF), QRS duration (QRSd), and LVMD were explored. In total, 78 patients and 60 healthy individuals (group 3) were enrolled. The patients were classified into two subgroups: LVEF≤35% (group 1), 35%0.05). CHF patients have different extents of LVMD. Longitudinal deformation shows the best detectability of dyssynchrony motion. Left ventricular systolic function was closely related to mechanical dyssynchrony, whereas QRSd showed no significant correlation.

[HIV-1 drug-resistance profiles of treated AIDS patients in Liaoning: genetic characteristics and prevalence].

OBJECTIVE: Since the advent in 2004 of highly active antiretroviral therapy (HAART) in Liaoning, a dramatic improvement had been seen in the number of patients attaining undetectable viral loads (92/104), but the extent of mutation diversity on human immunodeficiency virus 1 (HIV-1) and the prevalence of drug resistance had remained elusive. This study aimed to analyze both HIV-1 mutation profiles and prevalence related to antiretroviral resistance following therapeutic failure. METHODS: A total of 104 blood samples circling Liaoning from HAART-treated between 2004 and 2008 were studied. Patients' CD(4)(+) T-cell count and viral load were determined. HIV-1 pol (PR and part of RT) gene fragments were amplified from patients' plasma by reverse transcriptase polymerase chain reaction (RT-PCR) and nest-PCR, subsequently sequenced and analyzed. RESULTS: CD(4)(+) T cell numbers and viral replication capacity were assessed. 88.4% (92/104) of the patients were successful after initial non-suppressive NRTI & NNRTI-based HAART regimens. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (6/104) drug-resistance mutations than those on nucleoside reverse transcriptase inhibitor (NRTI) regimens did (5/104). No protease-inhibitor (PI) drug resistance mutations developed. The whole rate of drug resistance mutations was about 6.73%. Subjects developing NNRTI-resistance (NNRTI-R) seemed more likely to develop drug-resistant viremia than with NRTI-based HAART. CONCLUSION: This finding might have implications in which that the prevalence of drug-resistance mutations was low but remained risk of transmission in HIV-infected therapeutic failure. Meanwhile, data from the present study showed that there was a high frequency of primary mutations, which offered resistance to nrti and nnrti. Monitoring patients with treatment failure seems an important tool in helping the physicians to improve their treatment schedule and to carry out epidemiological surveillance programs.