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In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction. Notably, studies evaluating guideline-directed medical therapy recently endorsed by guidelines in stable HF, including the 4 drug classes all together (i.e., betablocker, mineral corticoid antagonist, renin angiotensin inhibitors/neprilysin inhibitors, and sodium glucose transporter inhibitors), remain scarcely analyzed in ADVHF and New York Heart Association (NYHA) Class IV. Additionally, due to the common conditions associated with advanced stages, the balance between drug tolerance and potential benefits of the contemporary use of all agents is questioned. Therefore, less hard endpoints, such as exercise tolerance, quality of life (QoL) and self-competency, are not clearly demonstrated. Specific analyses evaluating outcome and rehospitalization of each drug provided conflicting results and are often limited to subjects with stable conditions and less advanced NYHA class. Current European Society of Cardiology/American Heart Association (ESC/AHA) Guidelines do not indicate the type of treatment, dosage, and administration modalities, and they do not suggest specific indications for ADVHF patients. Due to these concerns, there is an impelling need to understand what drugs may be used as the first line, what management leads to the better outcome, and what is the best treatment algorithm in this setting. In this paper, we summarize the most common pitfalls and limitations for the use of the traditional agents, and we propose a personalized approach aiming at preserve drug tolerance and maintaining adverse event protection and satisfactory QoL. [ABSTRACT FROM AUTHOR]

Background: Current immunotherapy strategies have contrasting clinical results in human lung cancer patients as small-cell lung cancers (SCLC) often show features of immunological cold tumours. Topoisomerase 1 (TOP1) poisons are effective antitumor drugs with good efficacy against lung cancers.Methods: We used molecular, genetic and bioinformatic approaches to determine the mechanism of micronuclei formation induced by two TOP1 poisons in different human cancer cells, including SCLC cell lines.Results: TOP1 poisons stimulate similar levels of micronuclei in all tested cell lines but downstream effects can vary markedly. TOP1 poisons increase micronuclei levels with a mechanism involving R-loops as overexpression of RNaseH1 markedly reduces or abolishes both H2AX phosphorylation and micronuclei formation. TOP1 poison-induced micronuclei activate the cGAS/STING pathway leading to increased expression of immune genes in HeLa cells, but not in human SCLC cell lines, mainly due to lack of STING and/or cGAS expression. Moreover, the expression of STING and antigen-presenting machinery genes is generally downregulated in patient tumours of human lung cancer datasets.Conclusions: Altogether, our data reveal an immune signalling mechanism activated by TOP1 poisons, which is often impaired in human SCLC tumours. [ABSTRACT FROM AUTHOR]

Abstract  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. [ABSTRACT FROM AUTHOR]

An experimental investigation was performed to characterise the fat fraction of bouillon cubes. Besides the routine analyses, the analytical methods used were: silica-gel column chromatography to separate polar compounds, high performance size-exclusion chromatography (HPSEC) for the qualitative and quantitative determination of the single classes of substances constituting the polar compounds, and gas chromatography to determine the acid composition and the trans isomers of unsaturated fatty acids. The fats blended into the bouillon preparations were highly variable and were mainly made up of refined vegetable oils that had undergone hardening, by hydrogenation in most cases. Determination of the free fatty acids and of the peroxide values yielded figures that in some cases exceeded the limits set for the commercialisation of refined vegetable oils. Compared to the routine analyses, the HPSEC analysis of the polar compounds provided a better evaluation of the level of degradation of the fat extracted from the bouillon formulations. The levels of oxidative and hydrolytic degradation were rather high, and similar to those reported for poor quality oils. Analyses of the trans isomers of oleic acid yielded particularly high values (even over 20%) and differentiated the cubes on the basis of the type of fat added. [ABSTRACT FROM AUTHOR]