Synthesis and biological evaluation of novel isothiazoloquinoline quinone analogues.

Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.

Isobaric tag for relative and absolute quantitation-based comparative proteomic analysis of human pathogenic Prototheca zopfii genotype 2 and environmental genotype 1 strains.

BACKGROUND/PURPOSE: Prototheca species are ubiquitous achlorophyllic microalgae belonging to the family Chlorellaceae, which can cause a wide range of infections in humans and animals. Mainly in individuals with immunologic defects or trauma, Prototheca spp. can cause even lethal diseases. However, the exact pathogenic mechanism of Prototheca in causing disease remains largely unknown. To investigate the differences between pathogenic and nonpathogenic Prototheca spp. genotypes on proteome level, a nonpathogenic Prototheca zopfii genotype 1 strain, isolated from cow manure, and a human pathogenic P. zopfii genotype 2, isolated from human granulomatous lymphadenitis, were studied. METHODS: Differentially expressed proteins between the two genotypes were quantified by isobaric tag for relative and absolute quantitation-based quantitative proteomics, using liquid chromatography-tandem mass spectrometry. RESULTS: A total of 245 proteins were identified from the proteomic analysis after data filtering to eliminate low-scoring spectra. Among these, 35 proteins that displayed a significant (p<0.05) 1.5-fold change were considered as differentially expressed proteins. CONCLUSION: The differentially expressed proteins were associated with suppressed energy production and conversion, carbohydrate transport and metabolism, and enhanced translation in the genotype 2 strain, and are thus potentially relevant in the pathogenic mechanism of P. zopfii genotype 2, but need further investigation.

[Clinical application of extracorporeal shock wave to repair and reconstruct osseous tissue framework in the treatment of avascular necrosis of the femoral head (ANFH)].

OBJECTIVE: To investigate the application value of extracorporeal shock wave to repair and reconstruct osseous tissue for the treatment of avascular necrosis of the femoral head (ANFH). METHODS: A total of 42 hips of 36 patients with ANFH were treated with extracorporeal shock waves included 29 males and 7 females,aged from 21 to 66 during March 2006 to March 2008. The course of disease was 6 months to 3 years (means 1.3 years). According to Ficat classification 8 hips were in stages I, 25 were in stage II, and 9 were in stage III. The energy density of ESWT was from 0.18 to 0.25 mJ/mm2. The treatment focusing points of avascular necrosis of the femoral on the surface projection were marked with X-ray fluoroscopy, and 1 to 2 points were selected for one treatment with 400 to 500 pulses in each point. Generally 3 to 5 treatments were performed, once per 7 days. The CR, CT or MRI and the hip Harris score were obtained to investigate the clinical effects of extracorporeal shock wave for repair and reconstruct osseous tissue framework and improve the hip function before treatment and at 3, 12 months after treatment. RESULTS: The X-ray,CT or MR were performed of 42 hips,35 hips were treated successfully after extracorporeal shock wave therapy, cure occurred in 6 cases, marked effect in 13 cases, effectiveness in 16 cases and ineffectiveness in 7 case. After one years of followed-up, no relapse was found, the femoral head further collapse did not occur. The Harris hip score of stage I, II, III ere respectivey (90.1 +/- .4), (81.2 +/- .5), (66.9 +/- .6) at 3 months and (91.6 +/- .4), (91.1 +/- .5), (79.0 +/- .1) at 12 months after treatment. The scores after treatment were increased significantly than that of before treatment (P < 0.01). CONCLUSION: Extracorporeal shock wave therapy has obviously therapeutic effect in the repairing and reconstructing osseous tissue and improve the hip Harris score and improve the hip function. It is a effect significantly, non-invasion, less complications, simple-accurate therapy method for ischemic necrosis of the femoral head.