Risk Factors and Cellular Differences in Heart Failure: The Key Role of Sex Hormones

Patients with heart failure are conventionally stratified into phenotypic groups based on their ejection fraction. The aim of this stratification is to improve disease management with a more targeted therapeutic approach. A further subdivision based on patient gender is justified. It is recognized that women are underrepresented in randomized controlled clinical trials, resulting in limited clinical and molecular differentiation between males and females. However, many observational studies show that the onset, development, and clinical course of the disease may substantially differ between the two sexes. According to the emerging concept of precision medicine, investigators should further explore the mechanisms responsible for the onset of heart failure due to sex differences. Indeed, the synergistic or opposing effects of sex hormones on the cardiovascular system and underlying heart failure mechanisms have not yet been clarified. Sex hormones, risk factors impact, and cardiovascular adaptations may be relevant for a better understanding of the intrinsic pathophysiological mechanisms in the two sexes. Despite the differences, treatment for HF is similar across the whole population, regardless of sex and gender. In our review, we describe the main differences in terms of cardiovascular dysfunction, risk factors, and cellular signaling modifications related to the hormonal pattern

Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer Therapies

The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor knowledge of its biology. For several years, sorafenib, a tyrosine kinase inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for advanced HCC patients. Its activity is the inhibition of the retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. However, the efficacy of sorafenib is limited by the development of drug resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a critical and central role in HCC escape from TKIs activity. Advanced HCC patients with a BRAF mutation display a multifocal and/or more aggressive behavior with resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF could be another mechanism of cancer proliferation and TKI escape in HCC and the inhibition could become a possible strategy treatment for HCC. Moreover, recent preclinical studies and clinical trials evidence that combined treatments, involving alternative pathways, have an important role of therapy for HCC and they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). These initial data must be confirmed in clinical studies, which are currently ongoing. Translational research discoveries could create new strategies of targeted therapy combinations, including BRAF pathway, and they could eventually bring light in new treatment of HCC

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12–76.3) and 6.8 months (95% CI 2.7–24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC

Non-conventional Parameters for Quality Evaluation of Refined Olive Oil and Olive Oil Commercial Classes???

The analytical parameters to ascertain olive oil quality and classify olive oils are defined by the EC Regulation No 1989/2003. A table demonstrates that hydrolytic degradation is assessed by the percent free fatty acids (FFA); although this analysis is very useful and effective to attribute the commercial class to olive oils, it is not sufficient to define oil quality. Oxidative degradation is measured by the peroxide value (PV) and UV spectrophotometry. These analyses, however, take into account only few partial aspects of the complex phenomenon and do not meet the major need to know the actual state of oil oxidation based on the initiation, propagation and termination of the radical mechanism. This is even more relevant when one has to assess the quality of freshly refined oils. In such types of oils the percent FFA is not a reliable index, as FFA are removed during neutralization; nor is the determination of the PV viable because hydroperoxides are degraded and/or transformed by refinement, so that a freshly processed oil has a PV equal or very close to zero; this means that primary oxidation cannot be ascertained any longer by the PV. The use of plants' technological innovations would also influence these determinations. It seems thus necessary to have reliable analytical parameters for a more realistic assessment of quality. Reliable results have been obtained by the separation from oil of polar compounds (PC), which are constituted by substances having higher polarity than unaltered triglycerides. The subsequent HPSEC analysis of PC enables quantifying the following classes of substances: triglyceride oligopolymers (TGP), oxidized triglycerides (ox-TG), diglycerides (DG), sterols and triterpene diols, and FFA. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved

Pro-oxidant action of polar triglyceride oligopolymers in edible vegetable oils

The aim of the research was to evaluate the pro-oxidant action of oxidized triglyceride oliogopolymers, a class of oxidation compounds present in refined vegetable oils. Silica gel column chromatography was used to obtain the polar compounds from a thermally oxidized oil and preparative gel permeation chromatography to separate and collect the oxidized triglyceride oligopolymers. A purified oil that was practically free of oxidation and hydrolytic degradation products, pigments and anti-oxidants was prepared in the laboratory to evaluate pro-oxidant activity without interferences. Addition of percent amounts of oxidized triglyceride oligopolymers of 0.25 to 1.0% to both the purified and unpurified oils clearly evidenced the pro-oxidant activity of this class of compounds. © 2007 Springer-Verlag

Studio preliminare riguardante l’azione pro-ossidante di oligopolimeri di trigliceridi di natura polare negli oli alimentari

The pro-oxidant activity played by oxidised lipids in edible oils has already been reported in literature. However, it is still unknown whether all the classes of compounds due to oxidation and polimerisation, present in the oxidised fraction of a fat, have an equivalent pro-oxidant activity or if this activity is mainly performed by some of them. The aim of this research was that of evaluating the pro-oxidant effect of one of these classes, always present in refined oils, represented by the oligopolymers of oxidised triglycerides. Silica gel column chromatography was used to obtain the polar compounds (PC) from a thermo-oxidised oil, while preparative gel permeation chromatography of PC was carried out for separating and collecting the oligopolymers of oxidised triglycerides. A purified oil (not containing products of oxidation and hydrolytic degradation as well as free of pigments and substances having antioxidant activity) was prepared in laboratory with the aim to evaluate the pro-oxidant effect without interferences. The addition to the purified oil of variable percentages of polar triglyceride oligopolymers, in a range comprised between 0.25 and 1.0 %, fully evidenced the pro-oxidant activity of this class of compounds

The Oxidative State of Olive Oil Used in Bakery Products with Special Reference to Focaccia

The fatty substances used in bakery products vary a lot in nature and content. The most largely used lipids are butter, lard, hydrogenated vegetable oils, margarines, olive oil and olive-pomace oil; their content may range from 5 to 15% for some bread substitutes, such as focaccia, rusks, crackers, breadsticks, and up to 20-30% in the case of pastry products, such as biscuits and cakes. The choice of the most suitable kind of lipid and the optimal amount needed in the formulation is closely related to the desired bakery product, and is based on different parameters such as the dough workability, the product's rheological and sensory properties, the shelf-life and the consumers' needs. During the first processing step the "lipid binding" starts up: chemical and physical interactions are established between the lipids and other ingredients, such as starch and proteins (gluten). This process also involves free endogenous lipids (naturally contained in flours), i.e., lipids not chemically bound to cell structures or to other meal components. The formation of gliadine-lipid-glutenine complexes allows the dough to incorporate the gases, which develop during fermentation, and to retain them in the gluten mesh, thus giving volume and softness to the leavened product. © 2010 Copyright © 2010 Elsevier Inc. All rights reserved