Potential anti-cancer and anti-Candida activity of Zn-derived foams.

Zinc (Zn)-derived foams have been prepared from an alkaline electrolyte solution by galvanostatic electrodeposition under different conditions. A detailed physico-chemical characterization was performed by Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). A pioneer application of these foams in medical implant-related applications was investigated. The in vitro behaviour of these Zn-derived foams in simulated physiological conditions was studied. The results revealed that the presence of zinc oxide was important enough to change the in vitro behaviour of these materials. The potential of these Zn-derived foams in inhibiting bone cancer cell proliferation - osteoscarcoma cells - and important pathogenic fungi responsible for implant-related infections -Candida albicans- was examined. Furthermore, the foams were evaluated for cytocompatibility with normal human osteoblasts. The results obtained allowed us to conclude that Zn-derived foams have an interesting potential for anti-cancer and anti-Candida activity, targeted for bone-related implant applications, suggesting that this novel material may have potential for further clinical studies.

The SPI1 gene, encoding a glycosylphosphatidylinositol-anchored cell wall protein, plays a prominent role in the development of yeast resistance to lipophilic weak-acid food preservatives.

The Saccharomyces cerevisiae SPI1 gene encodes a member of the glycosylphosphatidylinositol-anchored cell wall protein family. In this work we show results indicating that SPI1 expression protects the yeast cell from damage caused by weak acids used as food preservatives. This is documented by a less extended period of adaptation to growth in their presence and by a less inhibited specific growth rate for a parental strain compared with a mutant with SPI1 deleted. Maximal protection exerted by Spi1p against equivalent concentrations of the various weak acids tested was registered for the more lipophilic acids (octanoic acid, followed by benzoic acid) and was minimal for acetic acid. Weak-acid adaptation was found to involve the rapid activation of SPI1 transcription, which is dependent on the presence of the Msn2p transcription factor. Activation of SPI1 transcription upon acetic acid stress also requires Haa1p, whereas this recently described transcription factor has a negligible role in the adaptive response to benzoic acid. The expression of SPI1 was found to play a prominent role in the development of yeast resistance to 1,3-beta-glucanase in benzoic acid-stressed cells, while its involvement in acetic acid-induced resistance to the cell wall-lytic enzyme is slighter. The results are consistent with the notion that Spi1p expression upon weak-acid stress leads to cell wall remodeling, especially for the more lipophilic acids, decreasing cell wall porosity. Decreased cell wall porosity, in turn, reduces access to the plasma membrane, reducing membrane damage, intracellular acidification, and viability loss.

Saccharomyces cerevisiae adaptation to weak acids involves the transcription factor Haa1p and Haa1p-regulated genes.

The understanding of the molecular mechanisms that may contribute to counteract the deleterious effects of organic acids as fungistatic agents is essential to guide suitable preservation strategies. In this work, we show that the recently identified transcription factor Haa1p is required for a more rapid adaptation of a yeast cell population to several weak acid food preservatives. Maximal protection is exerted against the short-chain length acetic or propionic acids. The transcription of nine Haa1p-target genes, many of which are predicted to encode membrane proteins of unknown or poorly characterized function, is activated under weak acid stress. The Haa1-regulated genes required for a more rapid yeast adaptation to weak acids include TPO2 and TPO3, encoding two predicted plasma membrane multidrug transporters of the major facilitator superfamily, and YGP1, encoding a poorly characterized cell wall glycoprotein. The acetic acid-induced prolongation of the lag phase of unadapted cell populations lacking HAA1 or TPO3, compared with wild-type population, was correlated with the level of the acid accumulated into the stressed cells.