The candidacidal activity of histatin 5 is initiated through cell wall binding, followed by translocation and intracellular targeting, while the halocidin peptide exerts its activity by attacking the Candida cell membrane. To improve antimicrobial activities and to understand the killing mechanism of two peptides, six hybrid peptides were designed by conjugating histatin 5 and halocidin. A comparative approach was established to study the activity, salt tolerance, cell wall glucan binding assay, cytotoxicity, generation of ROS and killing kinetics. CD spectrometry was conducted to evaluate secondary structures of these hybrid peptides. Furthermore the cellular localization of hybrid peptides was investigated by confocal fluorescence microscopy. Of the six hybrid congeners, di-PH2, di-WP2 and HHP1 had stronger activities than other hybrid peptides against all tested Candida strains. The MIC values of these peptides were 1–2, 2–4 and 2–4 μg/ml, respectively. Moreover, none of the hybrid peptides was cytotoxic in the hemolytic assay and cell-based cytotoxicity assay. Confocal laser microscopy showed that di-PH2 and HHP1 were translocated into cytoplasm whereas di-WP2 was accumulated on surface of C. albicans to exert their candidacidal activity. All translocated peptides (Hst 5, P113, di-PH2) were capable of generating intracellular ROS except HHP1. Additionally, the KFH residues at C-terminal end of these peptides were assumed for core sequence for active translocation.

Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drug-sensitive or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis activity against drug-sensitive strains (MIC, 3.125-6.25 μg/ml) as well as drug-resistant strains (MIC, 6.25 to 12.5 μg/ml). In addition, tamoxifen profoundly decreased the number of intracellular TB in macrophages in a dose-dependent manner.

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Granular shape biphasic calcium phosphate (BCP) bone grafts with and without doping of silicon cations were evaluated in regards to biocompatibility and MG-63 cellular response. To do this we studied Cellular cytotoxicity, cellular adhesion and spreading behavior and cellular differentiation with alizarin red S staining. Gene expression in MG-63 cells on the implanted bone substitutes was also examined at different time points using RT-PCR. In comparison, the Si-doped BCP granule showed more cellular viability than the BCP granule without doping in MTT assay. Moreover, cell proliferation was much higher when Si doping was employed. The cells grown on the silicon-doped BCP substitutes had more active filopodial growth with cytoplasmic webbing that proceeded to the flattening stage, which was indicative of well cellular adhesion. When these cells were exposed to Si-doped BCP granules for 14 days, well differentiated MG-63 cells were observed. Osteonectin and osteopontin genes were highly expressed in the late stage of differentiation (14 days), whereas collagen type I mRNA were found to be highly expressed during the early stage (day 3). These combined results of this study demonstrate that silicon-doped BCP enhanced osteoblast attachment/spreading, proliferation, differentiation and gene expression.

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