Sidechain Diversification of Grandifloracin Allows Identification of Analogues with Enhanced Anti-Austerity Activity against Human PANC-1 Pancreatic Cancer Cells

The natural product (+)-grandifloracin is a potent “anti-austerity” agent, able to suppress the ability of various pancreatic cancer cell lines to tolerate conditions of nutrient deprivation. Such anti-austerity agents represent a promising approach to cancer chemotherapy. Here we report the synthesis and biological evaluation of racemic analogues of grandifloracin bearing diverse sidechains, of which two show enhanced potency in comparison with the natural product. Additionally, several unexpected by-products containing modifications of the grandifloracin core were isolated, identified and similarly evaluated for biological activity.     

Predialysis and Dialysis Therapies Differently Affect Nitric Oxide Synthetic Pathway in Red Blood Cells from Uremic Patients: Focus on Peritoneal Dialysis

Red blood cells (RBCs) have been found to synthesize and release both nitric oxide (NO) and cyclic guanosine monophosphate (cGMP), contributing to systemic NO bioavailability. These RBC functions resulted impaired in chronic kidney disease (CKD). This study aimed to evaluate whether predialysis (conservative therapy, CT) and dialysis (peritoneal dialysis, PD; hemodialysis, HD) therapies used during CKD progression may differently affect NO-synthetic pathway in RBCs. Our data demonstrated that compared to PD, although endothelial-NO-synthase activation was similarly increased, HD and CT were associated to cGMP RBCs accumulation, caused by reduced activity of cGMP membrane transporter (MRP4). In parallel, plasma cGMP levels were increased by both CT and HD and they significantly decreased after hemodialysis, suggesting that this might be caused by reduced cGMP renal clearance. As conceivable, compared to healthy subjects, plasma nitrite levels were significantly reduced by HD and CT but not in patients on PD. Additionally, the increased carotid intima-media thickness (IMT) values did not reach the significance exclusively in patients on PD. Therefore, our results show that PD might better preserve the synthetic NO-pathway in CKD-erythrocytes. Whether this translates into a reduced development of uremic vascular complications requires further investigation.     

Functional implications of bound phenolic compounds and phenolics–food interaction: A review

Sizeable scientific evidence indicates the health benefits related to phenolic compounds and dietary fiber. Various phenolic compounds-rich foods or ingredients are also rich in dietary fiber, and these two health components may interrelate via noncovalent (reversible) and covalent (mostly irreversible) interactions. Notwithstanding, these interactions are responsible for the carrier effect ascribed to fiber toward the digestive system and can modulate the bioaccessibility of phenolics, thus shaping health-promoting effects in vivo. On this basis, the present review focuses on the nature, occurrence, and implications of the interactions between phenolics and food components. Covalent and noncovalent interactions are presented, their occurrence discussed, and the effect of food processing introduced. Once reaching the large intestine, fiber-bound phenolics undergo an intense transformation by the microbial community therein, encompassing reactions such as deglycosylation, dehydroxylation, α- and β-oxidation, dehydrogenation, demethylation, decarboxylation, C-ring fission, and cleavage to lower molecular weight phenolics. Comparatively less information is still available on the consequences on gut microbiota. So far, the very most of the information on the ability of bound phenolics to modulate gut microbiota relates to in vitro models and single strains in culture medium. Despite offering promising information, such models provide limited information about the effect on gut microbes, and future research is deemed in this field.     

Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats’ eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.     

Smart Campus: Fostering the Community Awareness Through an Intelligent Environment

Mobile Networks and Applications - Interconnected computational devices in the Internet of Things (IoT) context make possible to collect real-time data about a specific environment. The IoT...     

Phenolic composition of virgin olive oils from cross breeding segregating populations

The evaluation and characterization of segregating populations is a critical step in olive breeding programs. In this work, phenolic profiles of virgin olive oils (VOOs) from segregating populations obtained by cross breeding in Cordoba (Spain) have been evaluated. Genotypes obtained from open pollination of the cultivar Manzanilla de Sevilla, and from crosses between the cultivars Arbequina × Arbosana, Picual × Koroneiki and Sikitita × Arbosana were tested. The phenolic composition was determined after liquid–liquid extraction with 60:40 v/v methanol–water and subsequent chromatographic analysis with ultraviolet (UV) detection of both absorption and fluorescence in a sequential configuration. Results for all studied compounds showed high degree of variability between genotypes, with a higher range of variation than the observed for the genitors. Most of the observed variability was attributable to differences in genotypes within crosses rather than among crosses. Some issues related to breeding strategies are discussed. Practical applications: Phenolic compounds are considered to be of paramount importance for the assessment of virgin olive oil quality due to their contribution to the nutraceutical and sensory profile of this natural food. This study focuses on the evaluation of the content of phenolic compounds in olive oils originated from cross breeding in an olive breeding program (Cordoba, Spain). This step is crucial to determine the range of variation of phenolic compounds and the selection of interesting genotypes with higher composition in total phenols or in an individual phenol targeted at a breeding program.