Paola Bontempo

The beneficial effects of antioxidant supplementation in enteral feeding in critically ill patients: A prospective, randomized, double-blind, placebo-controlled trial

We investigated whether intervention with antioxidant vitamins C and E in enteral feeding influenced oxidative stress and clinical outcome in critically ill patients. Two-hundred-sixteen patients expected to require at least 10 days of enteral feeding completed the study. One-hundred-five patients received enteral feeding supplemented with antioxidants, and 111 control patients received an isocaloric formula. Plasma lipoper-oxidation (by thiobarbituric acid reactive substances [TBARS] and prostaglandin F2&agr; isoprostane levels), low-density lipoprotein (LDL) oxidizability, and LDL tocopherol content were determined at baseline and at the end of the 10-day period. The clinical 28-day outcome was also assessed. Plasma TBARS and isoprostanes were 5.33 ± 1.26 nM/mL and 312 ± 68 pg/mL, respectively, before treatment and 2.42 ± 0.61 nM/mL and 198 ± 42 pg/mL after intervention (P < 0.01 for both comparisons). Antioxidants improved LDL resistance to oxidative stress by approximately 30% (the lag time before treatment was 87 ±23 min and was 118 ±20 min after treatment; P <0.04). There was a significantly reduced 28-day mortality after antioxidant intervention (45.7% in the antioxidant group and 67.5% in the regular-feeding group; P < 0.05). Isoprostanes may provide a sensitive biochemical marker for dose selection in studies involving antioxidants.

Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells

Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone‐responsive cell functions and viability. We used high‐density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17β‐estradiol (E2), ICI 182,780 (ICI), 4OH‐tamoxifen (Tamoxifen), and raloxifene (RAL) in ER‐positive ZR‐75.1 cells, a suitable model to investigate estrogen and antiestrogen actions in hormone‐responsive BC. The expression of 601 genes was significantly affected by E2 in these cells; in silico analysis reveals that 86 among them include one or more potential ER binding site within or near the promoter and that the binding site signatures for E2F‐1, NF‐Y, and NRF‐1 transcription factors are significantly enriched in the promoters of genes induced by estrogen treatment, while those for CAC‐binding protein and LF‐A1 in those repressed by the hormone, pointing to novel transcriptional effectors of secondary responses to estrogen in BC cells. Interestingly, expression of 176 E2‐regulated mRNAs was unaffected by any of the antiestrogens tested, despite the fact that under the same conditions the transcriptional and cell cycle stimulatory activities of ER were inhibited. On the other hand, of 373 antiestrogen‐responsive genes identified here, 52 were unresponsive to estrogen and 25% responded specifically to only one of the compounds tested, revealing non‐overlapping and clearly distinguishable effects of the different antiestrogens in BC cells. As some of these differences reflect specificities of the mechanism of action of the antiestrogens tested, we propose to exploit this gene set for characterization of novel hormonal antagonists and selective estrogen receptor modulators (SERMs) and as a tool for testing new associations of antiestrogens, more effective against BC. J. Cell. Biochem. 98: 1163–1184, 2006.

Antioxidant, antimicrobial and anti-proliferative activities of Solanum tuberosum L. var. Vitelotte

Solanum tuberosum L. var. Vitelotte is a potato variety widely used for human consumption. The pigments responsible for its attractive color belong to the class of anthocyanins. The objectives of this study were to characterize and measure the concentration of anthocyanins in pigmented potatoes and to evaluate their antioxidant and antimicrobial activities and their anti-proliferative effects in solid and hematological cancer cell lines. Anthocyanins exert anti-bacterial activity against different bacterial strains and a slight activity against three fungal strains. The Gram-positive bacterium Staphylococcus aureus and the fungus Rhyzoctonia solani were the most affected microorganisms. Antioxidant activities were evaluated by DPPH and FRAP methods; the extract showed a higher reducing capability than anti-radical activity. Moreover, we found that in different cancer cell models the anthocyanins cause inhibition of proliferation and apoptosis in a dose dependent manner. These biological activities are likely due to the high content of malvidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside and petunidin 3-O-p-coumaroyl-rutinoside-5-O-glucoside.

Effect of Bisphenol A with or without enzyme treatment on the proliferation and viability of MCF-7 cells

Recently, aqueous solutions polluted by BPA have been bioremediated by us using laccase immobilized on hydrophobic membranes in non-isothermal bioreactors. BPA degradation was checked using analytical methods. To assess in vitro the occurred bioremediation, the proliferation and viability indexes of MCF-7 cells incubated in the presence of aqueous solutions of BPA, or of enzyme-treated BPA solutions, have been measured as a function of the initial BPA concentration. The results demonstrated that: i) at each initial BPA concentration used, both the proliferation and viability indexes are a function of the duration of enzyme treatment; ii) proliferation and viability are uncoupled biological processes with respect to BPA enzyme treatment. Non-isothermal bioreactors are a useful tool for the bioremediation of aqueous solutions polluted by BPA, which is an example of an endocrine disruptor that belongs to the alkyl phenol family.

CYP17 and CYP19 gene polymorphisms in women affected with endometriosis

OBJECTIVE To investigate whether CYP17 T>C polymorphism and polymorphisms C1558T and Val80 of CYP19 are related to endometriosis. DESIGN Clinical study. PATIENT(S) Women affected with endometriosis (n = 104) and control group (n = 86). The diagnosis of endometriosis was confirmed by the histologic examination of the endometriotic lesions. RESULT(S) In patients affected with endometriosis, we observed that AA and CC genotypes were significantly represented in Val80 and C1558T polymorphisms of CYP19. CONCLUSION(S) The molecular mechanisms that underlie the development of endometriosis are unclear. Both environmental and genetic factors are involved in the pathogenesis of the disease. The inheritable susceptibility to endometriosis justifies the growing interest in identifying genes and/or genetic polymorphisms that predispose women to an increased risk of developing endometriosis. The identification of single-nucleotide polymorphism (SNP), probably linked to endometriosis, could help to explain its pathogenesis.

Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin

Lichens are valuable natural resources used for centuries throughout the world as medicine, food, fodder, perfume, spices and dyes, as well as for other miscellaneous purposes. This study investigates the antiproliferative, antibacterial and antifungal activity of the acetone extract of the lichen Xanthoria parietina (Linnaeus) Theodor Fries and its major secondary metabolite, parietin. The extract and parietin were tested for antimicrobial activity against nine American Type Culture Collection standard and clinically isolated bacterial strains, and three fungal strains. Both showed strong antibacterial activity against all bacterial strains and matched clinical isolates, particularly against Staphylococcus aureus from standard and clinical sources. Among the fungi tested, Rhizoctonia solani was the most sensitive. The antiproliferative effects of the extract and parietin were also investigated in human breast cancer cells. The extract inhibited proliferation and induced apoptosis, both effects being accompanied by modulation of expression of cell cycle regulating genes such as p16, p27, cyclin D1 and cyclin A. It also mediated apoptosis by activating extrinsic and intrinsic cell death pathways, modulating Tumor Necrosis Factor-related apoptosis-inducing ligand (TRAIL) and B-cell lymphoma 2 (Bcl-2), and inducing Bcl-2-associated agonist of cell death (BAD) phosphorylation. Our results indicate that Xanthoria parietina is a major potential source of antimicrobial and anticancer substances.

Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation

Objectives:  Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava’s anti‐cancer potential and identified the parts of the fruit involved in its anti‐neoplastic action.

Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells

Background:BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) is present in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA. Thus, it is necessary to investigate the cytotoxicity and apoptosis-inducing activity of this compound.Methods:Cell cycle, apoptosis and differentiation analyses; western blots.Results:BPA is able to induce cell cycle arrest and apoptosis in three different acute myeloid leukemias. Although some granulocytic differentiation concomitantly occurred in NB4 cells upon BPA treatment, the major action was the induction of apoptosis. BPA mediated apoptosis was caspase dependent and occurred by activation of extrinsic and intrinsic cell death pathways modulating both FAS and TRAIL and by inducing BAD phosphorylation in NB4 cells. Finally, also non genomic actions such as the early decrease of both ERK and AKT phosphorylation were induced by BPA thus indicating that a complex intersection of regulations occur for the apoptotic action of BPA.Conclusion:BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.

Natural compounds in epigenetics: A current view

The successful treatment of many human diseases, including cancer, has come to be considered a major challenge, as patient response to therapy is difficult to predict. Recently, considerable efforts are being focused on the development of new tools to meet the growing demand for personalized medicine. With few exceptions, synthetic compounds have been unable to meet initial expectations for their clinical use. The last twenty years have been characterized by the failure of several drugs in advanced clinical development, possibly due to the insufficient understanding of molecular pathways underlying their mechanism of action. Although the biodiversity of compounds found in nature has been poorly explored until now, the field of naturally occurring drugs is rapidly expanding. Here, we review the current knowledge on the use of natural compounds with particular emphasis on those that display a chromatin remodeling effect coupled with anticancer action.

Genista sessilifolia DC. extracts induce apoptosis across a range of cancer cell lines

Restorative properties of medicinal plants such as Genista sessilifolia DC. have often been suggested to occur, in epidemiological studies. However, full characterization of effective principles responsible for this action has never previously been performed. Here, we have characterized G. sessilifolias anti‐cancer effects and identified the chemical components involved in this anti‐tumour action.