Targeting Breast Cancer: An Overlook on Current Strategies.

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. Surgery, radiotherapy, and chemotherapy are the main treatments for BC, even though the latter are often not aways successful because of the common side effects and the damage caused to healthy tissues and organs. Aggressive and metastatic BCs are difficult to treat, thus new studies are needed in order to find new therapies and strategies for managing these diseases. In this review, we intend to give an overview of studies in this field, presenting the data from the literature concerning the classification of BCs and the drugs used in therapy for the treatment of BCs, along with drugs in clinical studies.

Starch films loaded with tannin: the study of rheological and physical properties.

Recently, the research on innovative food packaging has been oriented toward biodegradable materials to lower the environmental impact generated by conventional plastics. The films often carry functional additives interacting with the matrix and modifying its physical properties. In this work tannin, a scarcely exploited active additive, was used to obtain potato starch-based films, and its content was optimized on the basis of mechanical and microscopic tests. Rheological measurements were adopted to evaluate the tannin-starch interaction and the microstructure of the film forming solutions (FFSs). Their thickness, color, thermal conductivity, elastic modulus (Eel), elongation at break (EAB), surface wettability and water solubility were evaluated. Furthermore, microstructure was investigated through Fourier-transform infrared spectroscopy (FTIR), polarized light (POM) and scanning electron microscopy (SEM). It was observed that all FFSs behave as weak gels and tannin addition weakens the gel structure and decreases the gelatinization temperature from about 60 °C to 57 °C. Plastic and deformable films (Eel = 1.96 MPa and EAB = 189 %) were obtained at low tannin fractions, whereas, at a higher concentration, stiffer films (Eel = 12 MPa and EAB = 10 %), with hydrophobic behavior were produced. Among the tested tannin fractions, an intermediate value of 1.7 % (w/w) was found to be promising for industrial purposes.

Interfacial Rheological Study of ß-Casein/Pectin Mixtures at the Air/Water Interface.

Colloidal food products, such as emulsions, foams, gels, and dispersions, are complex systems that need the presence of stabilizing agents to enable their formation and provide stability. Proteins are often used for food foams and emulsions because of their ability to lower interfacial tension and make viscoelastic interfaces. Generally, to improve the resistance against rupture, polysaccharides are used in association with the proteins. Pectin is a complex polysaccharide that can help to stabilize foams or emulsions. This work aims at studying the mechanical resistance of the interface formed by mixtures of ß-casein and pectin at high and low methoxylation degrees at the air/water interface using dilatational and shear kinematics. Frequency sweep tests, in the linear region, were performed in shear at different aging times and in dilatational mode, and the rheological data were analyzed. The transient data of the surface tension were analyzed by kinetic models to obtain the characteristic rates of the interfacial phenomena. The kinetic mechanisms of the protein/pectin mixed systems are controlled by protein and show a weak gel behavior for short aging times. The interfaces obtained with both pectins in a mixture with ß-casein evolved with time, gelling and showing a solid-like behavior at concentrations of 1 and 10 g/L and after 3.5 h of aging time. The interfacial shear trend obtained suggests a good stabilizing effect of the pectins from citrus with long aging times.

Interfacial behavior of vegetable protein isolates at sunflower oil/water interface.

Proteins are widely used in the formation and stabilization of multiphase systems, thanks to their ability to adsorb at the interface reducing the interfacial tension and promoting the formation of viscoelastic layers. Owing to the growing consumer demand, the food industry is moving toward the growing use of plant-based proteins, suitable for consumers who do not eat products of animal origin, for either ethical or health reasons. Nevertheless, the scientific literature lacks information on the surface activity and emulsifying ability of these proteins. In this work, the interfacial properties of soy, hemp and brown rice isolate proteins were investigated at the interface with commercial sunflower oil (O/W) to evaluate their characteristics in view of potential uses in food applications such as emulsions, sauces, dressing, topping and soft foods. Dilatational and shear kinematic, with pendant drop and magnetic rod techniques, respectively, were used. The dilatational analysis was performed in static and dynamic conditions, to obtain the equilibrium adsorption isotherms and the rheological parameters of the interfacial layers under both oscillation and stress relaxation. The interfaces were studied in shear conditions with small amplitude oscillations and creep tests. The obtained results evidenced that all tested proteins are able to build a strong viscoelastic layer with properties comparable to those of animal proteins. Brown rice protein seems particularly effective in reducing the interfacial tension even if shear tests evidence that the interface is weaker than that obtained using hemp or soy protein. Hemp protein seems very promising for potential practical uses yielding intermediate interfacial tensions and strong viscoelastic layers.

Formulation Study on Edible Film from Waste Grape and Red Cabbage.

(1) Background: Recent research on the valorization of agro-industrial waste has attempted to obtain new products. Grape residue is a waste product used in the grape wine industry that is rich in anthocyanins, as well as leaves and waste parts from red cabbage processing. Anthocyanins, thanks to their various functionalities, can be recovered and used as active and intelligent agents in food packaging. Anthocyanins have antioxidant properties that help to prevent cardiovascular disease. (2) Methods: In this study, the process of extracting waste was studied using solvent and supercritical CO2 extraction. The obtained anthocyanins were used in starch-based food film formulations. Several formulations were studied using rheometric techniques and the effect of adding anthocyanins on optimal film formulation was investigated. (3) Results: Solvent extractions resulted in a maximum extraction yield. The extracts obtained were used for the preparation of coating and edible films, optimized in the formulation. (4) Conclusions: The addition of anthocyanins to films resulted in increased sample structuring and mechanical properties that are valid for applications, like dipping using coverage methods. The packaging is also attractive and pH-sensitive.

Phytochemical Profile and In Vitro Antioxidant and Photobiological Properties of Different Extracts from Prangos ferulacea Lindl.

Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO2 extraction showing the highest activity (IC50 = 4.91 µg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

Oil Extraction from Hemp Plant as a Potential Source of Cannabidiol for Healthy Protein Foods.

In recent years, the increasing demand for alternative foods has shifted research toward new sources enriched with nutraceutical molecules. It is well known that many diseases are caused by oxidative stress; thus, the supplementation of antioxidants has been proposed to reduce it. Cannabis sativa L. is an interesting species that could provide an alternative source of antioxidants. This work aimed to investigate the possibility of optimizing the yield of cannabidiol (CBD) and recovering it from residual biomass (stalks), valorizing the residual biomass, and using this for protein bar preparation. Different extraction methods were used, and High-Pressure Liquid Chromatography (HPLC) analysis was used to analyze the extracts. Antioxidant power was investigated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. The best results in terms of CBD yield were obtained via dynamic maceration after decarboxylation with a quantity of 26.7 ± 2 mgCBD/graw material from inflorescences. The extract also shows good antioxidant power with an IC50 value of 38.1 ± 1.1 µg/mL measured using the DPPH assay. The CBD extract was added to the hemp oil to obtain dough for protein bars. The doughs were studied by taking rheological and technological measurements, and it was found that the protein bars could provide an excellent means for the consumption of products enriched with antioxidants because their CBD anti-inflammatory activity is preserved after cooking.

Graphene-based nafion nanocomposite membranes: enhanced proton transport and water retention by novel organo-functionalized graphene oxide nanosheets.

Novel nanostructured organo-modified layered materials based on graphene oxide carrying various hydrophilic functional groups (-NH(2), -OH, -SO(3)H) are prepared and tested as nanofillers for the creation of innovative graphene-based Nafion nanocomposites. The hybrid membranes are characterized by a combination of analytical techniques, which show that highly homogeneous exfoliated nanocomposites are created. The pulsed field gradient NMR technique is used to measure the water self-diffusion coefficients. Remarkable behavior at temperatures up to 140 °C is observed for some composite membranes, thereby verifying the exceptional water retention property of these materials. Dynamic mechanical analysis shows that hybrid membranes are much stiffer and can withstand higher temperatures than pure Nafion.

Emulgels Structured with Dietary Fiber for Food Uses: A Rheological Model.

Emulgels are biphasic emulsified systems in which the continuous phase is structured with a specific gelling agent. In this work, a rheological and microscopic investigation of O/W emulgels prepared by structuring the aqueous (continuous) phase with citrus fiber was carried out with the aim of designing their macroscopic properties for food uses and predicting their characteristics with a rheological model. According to previous investigations, fiber suspensions behave as "particle gels" and, consequently, the derived emulgels' properties are strongly dependent on the fiber concentration and on process conditions adopted to produce them. Therefore, a rotor-stator system was used to prepare emulgels with increasing fiber content and with different levels of energy and power used for mixing delivered to the materials. An investigation of particle gels was then carried out, fixing the operating process conditions according to emulgel results. Furthermore, the effect of the dispersed (oil) phase volume fraction was varied and a modified semi-empirical Palierne model was proposed with the aim of optimizing a correlation between rheological properties and formulation parameters, fixing the process conditions.

An ACE2-Alamandine Axis Modulates the Cardiac Performance of the Goldfish Carassius auratus via the NOS/NO System.

Alamandine is a peptide of the Renin Angiotensin System (RAS), either generated from Angiotensin A via the Angiotensin Converting Enzyme 2 (ACE2), or directly from Ang-(1-7). In mammals, it elicits cardioprotection via Mas-related G-protein-coupled receptor D (MrgD), and the NOS/NO system. In teleost fish, RAS is known to modulate heart performance. However, no information is available on the presence of a cardioactive ACE2/Alamandine axis. To fill this gap, we used the cyprinid teleost Carassius auratus (goldfish) for in silico and in vitro analyses. Via the NCBI Blast P suite we found that in cyprinids ace2 is phylogenetically detectable in a subcluster of proteins including ace2-like isoforms, and is correlated with a hypoxia-dependent pathway. By real-time PCR, Western Blotting, and HPLC, ACE2 and Alamandine were identified in goldfish heart and plasma, respectively. Both increased after chronic exposure to low O2 (2.6 mg O2 L-1). By using an ex-vivo working goldfish-heart preparation, we observed that in vitro administration of exogenous Alamandine dose-dependently stimulates myocardial contractility starting from 10-11 M. The effect that involved Mas-related receptors and PKA occurred via the NOS/NO system. This was shown by exposing the perfused heart to the NOS inhibitor L-NMMA (10-5 M) that abolished the cardiac effect of Alamandine and was supported by the increased expression of the phosphorylated NOS enzyme in the extract from goldfish heart exposed to 10-10 M Alamandine. Our data are the first to show that an ACE2/Alamandine axis is present in the goldfish C. auratus and, to elicit cardiac modulation, requires the obligatory involvement of the NOS/NO system.

Opuntia ficus indica (L.) Mill. An Ancient Plant Source of Nutraceuticals.

Opuntia ficus-indica (L.) Mill. (OFI) is a plant with numerous beneficial properties known in traditional medicine. It has been a domesticated plant in Latin America, Africa, Mediterranean countries, the Middle East, India and Australia. Nowadays, the research concentrates on natural compounds to lower costs and the possible side effects of synthetic compounds. The use of nutraceuticals, bioactive compounds of vegetable origin with important nutritional values, is encouraged. OFI has shown numerous activities due to its high content of antioxidants, including flavonoids and ascorbate, pigments, carotenoids and betalains, phenolic acids and other phytochemical components, such as biopeptides and soluble fibers. The most important effects of OFI are represented by the activity against acne, arthrosis, dermatosis, diabetes, diarrhea, fever, high blood pressure, prostatitis, rheumatism, stomachache, tumor, wart, allergy, wound, colitis and some viral diseases. Moreover, a promising role has been suggested in inflammatory bowel disease, colitis and metabolic syndrome. The most recent studies addressed the role of OFI in preventing and treating COVID-19 disease. In light of the above, this review summarizes the biological activities and health benefits that this plant may exert.

Cardiac and Metabolic Impact of Functional Foods with Antioxidant Properties Based on Whey Derived Proteins Enriched with Hemp Seed Oil.

The impaired ability to feed properly, evident in oncologic, elderly, and dysphagic patients, may result in malnutrition and sarcopenia. Increasing the consumption of dietary proteins by functional foods and enriching their composition by adding beneficial nutrients may represent an adjuvant therapy. We aimed to evaluate the safety and the positive effects of a standard diet (SD) supplemented with whey-derived protein puddings (WDPP), with appropriate rheological properties, and hemp seed oil (HSO), rich in polyphenols. Rats were assigned to SD, WDPP, WDPP plus hemp seed oil (HSOP), and HSO supplemented diets for eight weeks. "Anthropometric", metabolic, and biochemical variables, oxidative stress, tissue injury, liver histology, and cardiac susceptibility to ischemia/reperfusion were analyzed. All the supplementations did not induce significant changes in biochemical and metabolic variables, also in relation to glucose tolerance, and livers did not undergo morphological alteration and injury. An improvement of cardiac post-ischemic function in the Langendorff perfused heart model and a reduction of infarct size were observed in WDPP and HSOP groups, thanks to their antioxidant effects and the activation of Akt- and AMPK-dependent protective pathways. Data suggest that (i) functional foods enriched with WDPP and HSOP may be used to approach malnutrition and sarcopenia successfully under disabling conditions, also conferring cardioprotection, and that (ii) adequate rheological properties could positively impact dysphagia-related problems.

The effects of intermolecular interactions on the physical properties of organogels in edible oils.

The microstructure of organogels based on monoglycerides of fatty acids (MAGs) and policosanol and on different edible oils was investigated by using different techniques (calorimetry, nuclear magnetic resonance, infrared spectroscopy, rheology, polarized light microscopy) towards a better understanding and control of the oil gelation phenomena. Dynamic moduli were related via a fractal model to microstructural information such as solid content and fractal dimension. Infrared spectroscopy evidenced that network structure in MAGs gel is mainly due to hydrogen bonding, whereas in policosanol system is mainly given by van der Waals interactions. Because of the different relative contribution of molecular interactions, the investigated organogelators exhibit a distinguished macroscopic behavior. MAGs are sensitive to the utilized oil and structuration occurs quickly, even though at a temperature lower than policosanol. Policosanol organogels exhibit a behavior independent of the used oil and a slower gelation rate, as a result of the weaker van der Waals interactions. Nevertheless, at lower concentration a stronger final gel is obtained, probably due to of the large number of interactions arising among the long alkyl chains of the fatty alcohols. Obtained results evidenced that policosanol is very effective in gelation of different oils and seems promising for potential commercial uses.

A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses.

Bigels are biphasic systems formed by water-based hydrogels and oil-based organogels, mainly studied, in the last few years, for pharmaceutical and cosmetic application focused on the controlled delivery of both lipophilic and hydrophilic active agents. The rheological properties of bigels depend on both the amount and the rheological characteristics of single structured phases. Moreover, it can be expected that, at large fractions of one of the starting gels, systems more complex than oil-in-water or water-in-oil can be obtained, yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were investigated from a microstructural (i.e. microscopy and electrical conductivity tests) and rheological point of view. The hydrogel was prepared by using a low-methoxyl pectin whereas the organogel was prepared by using olive oil and, as gelator, a mixture of glyceryl stearate and policosanol. Model bigels were obtained by increasing the amount of organogel mixed with the hydrogel, and microstructural characterisation evidenced an organogel-in-hydrogel behaviour for all investigated samples, even though at the highest organogel content a more complex structure seems to arise. A semi-empirical model, based on theoretical equations developed for suspensions of elastic spheres in elastic media, was proposed to relate bigel rheological properties to single phase properties and fractions.

Olive oil/policosanol organogels for nutraceutical and drug delivery purposes.

Low molecular weight organogels are semisolid systems structured by the assembly of molecules that crystallise under suitable process conditions. The inner microstructure of organogels is made up of a 3-D network, in which both an organic liquid solvent and other dispersed particles can be entrapped. In this work, olive oil organogels, structured from policosanol (a nutraceutical mixture of fatty alcohols), were studied in order to obtain the best formulation for producing a support for delivery of lipophilic agents (namely ferulic Acid) via oral administration. A rheological optimisation of the olive oil-policosanol organogel was first of all performed with Step Shear Rate Temperature Ramp tests. This provided important information on the policosanol fraction to be added to the system and on the onset of crystallisation temperature, an indirect measurement of the system melting point. It was found that a policosanol weight percentage of 0.03 was suitable to obtain contemporary semisolid organogels, consistent enough and thermally stable for human ingestion. In vitro tests on organogels loaded with ferulic acid were also carried out in order to simulate the oral intake of the nutraceutical compound. This evidenced a release mechanism determined by both erosion and diffusion; a good performance of gels and their ability to control the release rate through the degree of structuration were also observed.

Malvidin, a red wine polyphenol, modulates mammalian myocardial and coronary performance and protects the heart against ischemia/reperfusion injury.

A moderate red wine consumption and a colored fruit-rich diet protect the cardiovascular system, thanks to the presence of several polyphenols. Malvidin-3-0-glucoside (malvidin), an anthocyanidine belonging to polyphenols, is highly present in red grape skin and red wine. Its biological activity is poorly characterized, although a role in tumor cell inhibition has been found. To analyze whether and to which extent, like other food-derived polyphenols, malvidin affects the cardiovascular function, in this study, we have performed a quantitative analysis by high-performance liquid chromatography of polyphenolic content of red grape skins extract, showing that it contains a high malvidin amount (63.93 ±12.50 mg/g of fresh grape skin). By using the isolated and Langendorff perfused rat heart, we found that the increasing doses (1-1000 ng/ml) of the extract induced positive inotropic and negative lusitropic effects associated with coronary dilation. On the same cardiac preparations, we observed that malvidin (10(-10)-10(-6) mol/L) elicited negative inotropism and lusitropism and coronary dilation. Analysis of mechanism of action revealed that malvidin-dependent cardiac effects require the activation of the phosphatidylinositol 3-kinase (PI3K)/nitric oxide (NO)/cGMP/PKG pathway and are associated with increased intracellular cGMP and the phosphorylation of endothelial NO synthase (eNOS), PI3K-AKT, ERK1/2, and GSK-3ß. AKT and eNOS phosphorylation was confirmed in human umbilical vein endothelial cell. We also found that malvidin act as a postconditioning agent, being able to elicit cardioprotection against ischemia/reperfusion damages. Our results show the cardioactivity of polyphenols-rich red grape extracts and indicate malvidin as a new cardioprotective principle. This is of relevance not only for a better clarification of the beneficial cardiovascular effects of food-derived polyphenols but also for nutraceutical research.