Synthesis, in vitro antimicrobial and antioxidant activities of chalcone and flavone derivatives holding allylic substitutions

In a wide search program towards new and efficient biological active agents, a series of chalcone and flavone derivatives holding allylic substitutions have been synthesized and tested for their in vitro antibacterial and antifungal activities. The synthesized compounds were tested in vitro against Gram-positive, Gram-negative bacteria, and the yeast Candidia kefir in comparison with control drugs (Sulfamethoxazole and Fluconazole). The antioxidant activity of the synthesized allylic chalcones and flavones was also assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and reducing power assays and compared to reference drug Trolox.     

Conflicts of interest in research: is clinical decision-making compromised? An opinion paper

Lack of transparency in funded research can compromise clinical decision-making in an evidence-based practice. Transparency can be defined as full disclosure of all financial assistance and support to authors and investigators. There is a perception that ethical principles are eroding and that research data can be biased due to conflicts of interest. These research outcomes biased or not, are used for clinical decision-making in the evidence-based practice. One suggested solution to this common ethical dilemma is to continue the dialogue on transparency in research and to create oversight bodies which include representatives from business and industry, private practice, academia, and research. There is increasing evidence of the need for more ethics education at all levels.     

Placental biomarkers of phthalate effects on mRNA transcription: application in epidemiologic research

Background  

CYP19 and PPARγ are two genes expressed in the placental trophoblast that are important to placental function and are disrupted by phthalate exposure in other cell types. Measurement of the mRNA of these two genes in human placental tissue by quantitative real-time polymerase chain reaction (qPCR) offers a source of potential biomarkers for use in epidemiologic research. We report on methodologic challenges to be considered in study design.     

Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy

OBJECTIVES

To characterize changes in secretory clusterin (sCLU) expression in prostate cancer cells after treatment with docetaxel and to determine whether sCLU knockdown can re‐introduce chemosensitivity in a docetaxel‐resistant, androgen‐independent human prostate cancer model.

PATIENTS AND METHODS

A tissue microarray was constructed for 84 radical prostatectomy (RP) specimens from a multicentre Phase II trial of neoadjuvant combined androgen ablation and docetaxel (CUOG‐P01a) and assessed for changes in the expression of the cytoprotective chaperone sCLU. The human prostate cancer cell line PC‐3 was repeatedly exposed to docetaxel chemotherapy in vitro, and a docetaxel‐resistant cell subline (PC‐3dR) was developed and analysed.

RESULTS

sCLU levels were significantly higher in RP specimens treated with neoadjuvant combined androgen ablation and docetaxel than in untreated specimens. Similarly, sCLU expression increased 2.5‐fold in the newly developed docetaxel‐refractory PC‐3dR cell line compared with parental PC‐3 cells. There was a dose‐dependent and sequence‐specific decrease in sCLU levels in PC‐3dR cells using OGX‐011, an antisense oligonucleotide against human sCLU. OGX‐011 and small‐interference RNA both chemosensitized PC‐3dR cells to docetaxel and mitoxantrone in vitro and apoptotic rates in PC‐3dR cells were significantly increased when OGX‐011 was combined with docetaxel. In vivo, growth of PC‐3dR xenografts in nude mice was synergistically inhibited by OGX‐011 combined with paclitaxel or mitoxantrone (by 76% and 44% compared with their mismatch controls, respectively).

CONCLUSION

The present findings indicate that targeted knockdown of sCLU enhances the effects of cytotoxic chemotherapy in docetaxel‐refractory cells, and provide preclinical proof of principle for clinical trials testing OGX‐011 in second‐line chemotherapy regimens for patients with docetaxel‐refractory prostate cancer.     

Effects of dietary red clover on blood factors and cardiovascular fatty streak formation in hypercholesterolemic rabbits

Phytoestrogens with a biological activity like estradiol are naturally found in many plants. This study was designed to investigate the effect of red clover, a phytoestrogen-rich member of the legume family (Trifolium pratense) on the development of atherosclerosis in male hyperlipidemic rabbits. Twenty rabbits were semi-randomly distributed into four groups of five each. Two groups received either normal diet or normal diet supplemented with red clover. Two other groups received similar diets to both of which 1% cholesterol was added. Dietary use of red clover (RC) in hyperlipidemic rabbits significantly decreased C-reactive protein (CRP), triglyceride (TG), total cholesterol and LDL-cholesterol (LDL-C) whereas, HDL-cholesterol (HDL-C) was significantly increased in those animals (p < 0.05). Fatty streak formation was also significantly lower in aorta and left and right coronary arteries in the same animals due to use of dietary RC supplementation. These findings suggest that dietary RC may reduce cardiovascular risk factors.