The active phthalate metabolite, DHEP, induces proliferation and metastasis of prostate cancer cells via upregulation of ß-catenin and downregulation of KLF7.

Phthalates such as DHEP are among the widely used compounds in industry. It has been shown that DHEP can convey various biological consequences in mammalian cells, among them, the carcinogenic effects of DHEP are emphasized. The present study aimed to assess the impact of DHEP exposure on the proliferation and invasiveness of DU145 prostate cancer cells through in vitro and in vivo models. The DU145 cells were treated with increasing concentrations of DHEP and the tumorigenic parameters were analyzed. KLF7 as a probable mediator of the effect of DHEP was either overexpressed or knocked down in DU145 to evaluate the probable impact of KLF7 on the biological effects of DHEP. The effect of DHEP was also studied in a DU145 xenograft tumor model. The moderate doses of DHEP increased the proliferation and migration of DU145 cells. In the case of gene expression patterns, DHEP reduced the levels of p53 and KLF7 while elevated the expression of ß-catenin. The knock-down of KLF7 conveyed comparable effects to that of DHEP to some degree and increased the proliferation of DU145 cells, while the transduction of KLF7 increased the expressions of p53 and p21 along with controlling the tumor size. The present study demonstrated the potential of DHEP in increasing the tumorigenic properties of DU145 cells along with a focus on the underlying mechanisms. Sustained exposure to DHEP can cause a dysregulation in balance between oncogenes and tumor suppressor genes which is the hallmark of malignant transformation. Thus, special considerations seem necessary for the safe exploitation of phthalates.

An Engineered Multimodular Enzybiotic against Methicillin-Resistant Staphylococcus aureus.

Development of multidrug antibiotic resistance in bacteria is a predicament encountered worldwide. Researchers are in a constant hunt to develop effective antimicrobial agents to counter these dreadful pathogenic bacteria. Here we describe a chimerically engineered multimodular enzybiotic to treat a clinical isolate of methicillin-resistant Staphylococcus aureus (S. aureus). The cell wall binding domain of phage ϕ11 endolysin was replaced with a truncated and more potent cell wall binding domain from a completely unrelated protein from a different phage. The engineered enzybiotic showed strong activity against clinically relevant methicillin-resistant Staphylococcus aureus. In spite of a multimodular peptidoglycan cleaving catalytic domain, the engineered enzybiotic could not exhibit its activity against a veterinary isolate of S. aureus. Our studies point out that novel antimicrobial proteins can be genetically engineered. Moreover, the cell wall binding domain of the engineered protein is indispensable for a strong binding and stability of the proteins.

Trace Element Determination and Cardioprotection of Terminalia pallida Fruit Ethanolic Extract in Isoproterenol Induced Myocardial Infarcted Rats by ICP-MS.

The trace elements and minerals in Terminalia pallida fruit ethanolic extract (TpFE) were determined by the instrument inductively coupled plasma-mass spectrometry (ICP-MS), and the cardioprotection of TpFE against isoproterenol (ISO)-administered rats was studied. Rats were pretreated with TpFE (100, 300, and 500 mg/kg bw) for 30 days, with concurrent administration of ISO (85 mg/kg bw) for two consecutive days. The levels of trace elements and minerals in TpFE were below the permitted limits of World Health Organization standards. ISO administration significantly increased the heart weight and cardiac marker enzymes in serum, xanthine oxidase, sodium, and calcium in the heart, whereas significantly decreased body weight, reduced glutathione, glutathione-S-transferase, superoxide dismutase, and potassium in the heart. Oral pretreatment of TpFE significantly prevented the ISO-induced alterations. This is the first report that revealed the determination of trace elements and mineral nutrients of TpFE by ICP-MS which plays a principal role in the herbal drug discovery for the treatment of cardiovascular diseases.