Does hunted wild boar meat meet modern consumer nutritional expectations?

The present study aimed to evaluate the nutritional characteristics of hunted wild boar (WB) meat and compare them with those of meat from analogous domestic animals (pigs) reared in two different rearing systems: indoor-intensive (PI) and outdoor-extensive (PO). WB meat showed a lower amount of lipid content compared to pork and a higher antioxidant activity compared to PI and PO. The comparison of the fatty acid composition of WB and domestic pig reveals significant differences in saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), with WB having the highest PUFA level and the lowest SFA level. The omega 6/omega 3 (n-6/n-3) PUFA ratio, PUFA/SFA, atherogenic and thrombogenic indices (AI and TI), as well as the hypocholesterolemic/ hypercholesterolemic index (h/H), were calculated. The n-6/n-3 PUFA ratio was higher in pork independently of the rearing system. The PUFA/SFA ratio of WB meat was above the minimum ratio of 0.40 recommended to contribute to a reduction in the risk of coronary diseases in pork from both rearing systems. AI and TI were lower in WB meat compared to commercially reared pigs, while h/H was higher in WB in comparison with pork meat. WB meat shows good nutritional quality; therefore, the use of game meat as a food source could be appropriate and could benefit contemporary consumers looking for "green" and high-nutritional products.

Sphingomyelin Metabolism Modifies Luminal A Breast Cancer Cell Line under a High Dose of Vitamin C.

The role of sphingomyelin metabolism and vitamin C in cancer has been widely described with conflicting results ranging from a total absence of effect to possible preventive and/or protective effects. The aim of this study was to establish the possible involvement of sphingomyelin metabolism in the changes induced by vitamin C in breast cancer cells. The MCF7 cell line reproducing luminal A breast cancer and the MDA-MB-231 cell line reproducing triple-negative breast cancer were used. Cell phenotype was tested by estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 expression, and proliferation index percentage. Sphingomyelin was localized by an EGFP-NT-Lys fluorescent probe. Sphingomyelin metabolism was analyzed by RT-PCR, Western blotting and UFLC-MS/MS. The results showed that a high dose of vitamin C produced reduced cell viability, modulated cell cycle related genes, and changed the cell phenotype with estrogen receptor downregulation in MCF7 cell. In these cells, the catabolism of sphingomyelin was promoted with a large increase in ceramide content. No changes in viability and molecular expression were observed in MB231 cells. In conclusion, a high dose of vitamin C induces changes in the luminal A cell line involving sphingomyelin metabolism.

Valorization of Pumpkin Byproducts: Antioxidant Activity and Carotenoid Characterization of Extracts from Peel and Filaments.

Pumpkin (Cucurbita sp.) represents an unquestionable source of valuable nutrients and bioactive compounds having a broad spectrum of health-promoting effects. The goal of this work was to characterize the byproducts (peels and filaments) of different pumpkin varieties belonging to C. moschata (Butternut, Lunga di Napoli, Moscata di Provenza, and Violina rugosa) and C. maxima (Delica, Delica vanity, Hokkaido, and Mantovana) species in terms of total carotenoid content, antioxidant activity, and carotenoid profiling. The research revealed that peels and filaments were a good source of ß-carotene and other non-esterified carotenoids, as well as esterified carotenoids. Considering the growing market demand for safe and healthy food products, pumpkin byproducts, having also an interesting antioxidant bioactivity, could be useful in the development of novel functional products.

4D Printing Shape-Morphing Hybrid Biomaterials for Advanced Bioengineering Applications.

Four-dimensional (4D) printing is an innovative additive manufacturing technology used to fabricate structures that can evolve over time when exposed to a predefined environmental stimulus. 4D printed objects are no longer static objects but programmable active structures that accomplish their functions thanks to a change over time in their physical/chemical properties that usually displays macroscopically as a shapeshifting in response to an external stimulus. 4D printing is characterized by several entangled features (e.g., involved material(s), structure geometry, and applied stimulus entities) that need to be carefully coupled to obtain a favorable fabrication and a functioning structure. Overall, the integration of micro-/nanofabrication methods of biomaterials with nanomaterials represents a promising approach for the development of advanced materials. The ability to construct complex and multifunctional triggerable structures capable of being activated allows for the control of biomedical device activity, reducing the need for invasive interventions. Such advancements provide new tools to biomedical engineers and clinicians to design dynamically actuated implantable devices. In this context, the aim of this review is to demonstrate the potential of 4D printing as an enabling manufacturing technology to code the environmentally triggered physical evolution of structures and devices of biomedical interest.

The Effect of Cholesterol in MCF7 Human Breast Cancer Cells.

In the last decade, cholesterol level has been implicated in several types of cancer, including breast cancer. In the current study, we aimed to investigate the condition of lipid depletion, hypocholesterolemia or hypercholesterolemia reproduced in vitro to analyze the response of different human breast cancer cells. Thus, MCF7 as the luminal A model, MB453 as the HER2 model and MB231 as the triple-negative model were used. No effect on cell growth and viability was detected in MB453 and MB231 cells. In MCF7 cells, hypocholesterolemia (1) reduced cell growth, and Ki67 expression; (2) increased ER/PgR expression; (3) stimulated the 3-Hydroxy-3-Methylglutaryl-CoA reductase and neutral sphingomyelinase and; (4) stimulated the expression of CDKN1A gene coding cyclin-dependent kinase inhibitor 1A protein, GADD45A coding growth arrest and DNA-damage-inducible alpha protein and, PTEN gene coding phosphatase and tensin homolog. All these effects were exacerbated by the lipid-depleted condition and reversed by the hypercholesterolemic condition. The relationship between cholesterol level and sphingomyelin metabolism was demonstrated. In summary, our data suggest that cholesterol levels should be controlled in luminal A breast cancer.

Biomaterial Inks from Peptide-Functionalized Silk Fibers for 3D Printing of Futuristic Wound-Healing and Sensing Materials.

This study illustrates the sensing and wound healing properties of silk fibroin in combination with peptide patterns, with an emphasis on the printability of multilayered grids, and envisions possible applications of these next-generation silk-based materials. Functionalized silk fibers covalently linked to an arginine-glycine-aspartic acid (RGD) peptide create a platform for preparing a biomaterial ink for 3D printing of grid-like piezoresistors with wound-healing and sensing properties. The culture medium obtained from 3D-printed silk fibroin enriched with RGD peptide improves cell adhesion, accelerating skin repair. Specifically, RGD peptide-modified silk fibroin demonstrated biocompatibility, enhanced cell adhesion, and higher wound closure rates at lower concentration than the neat peptide. It was also shown that the printing of peptide-modified silk fibroin produces a piezoresistive transducer that is the active component of a sensor based on a Schottky diode harmonic transponder encoding information about pressure. We discovered that such biomaterial ink printed in a multilayered grid can be used as a humidity sensor. Furthermore, humidity activates a transition between low and high conductivity states in this medium that is retained unless a negative voltage is applied, paving the way for utilization in non-volatile organic memory devices. Globally, these results pave the way for promising applications, such as monitoring parameters such as human wound care and being integrated in bio-implantable processors.

The Polyunsaturated Fatty Acid EPA, but Not DHA, Enhances Neurotrophic Factor Expression through Epigenetic Mechanisms and Protects against Parkinsonian Neuronal Cell Death.

ω-3 Polyunsaturated fatty acids (PUFAs) have been found to exert many actions, including neuroprotective effects. In this regard, the exact molecular mechanisms are not well understood. Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Emerging evidence supports the hypothesis that PD is the result of complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction, and other cellular processes, such as DNA methylation. In this context, BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) have a pivotal role because they are both involved in neuron differentiation, survival, and synaptogenesis. In this study, we aimed to elucidate the potential role of two PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their effects on BDNF and GDNF expression in the SH-SY5Y cell line. Cell viability was determined using the MTT assay, and flow cytometry analysis was used to verify the level of apoptosis. Transmission electron microscopy was performed to observe the cell ultrastructure and mitochondria morphology. BDNF and GDNF protein levels and mRNA were assayed by Western blotting and RT-PCR, respectively. Finally, methylated and hydroxymethylated DNA immunoprecipitation were performed in the BDNF and GDNF promoter regions. EPA, but not DHA, is able (i) to reduce the neurotoxic effect of neurotoxin 6-hydroxydopamine (6-OHDA) in vitro, (ii) to re-establish mitochondrial function, and (iii) to increase BNDF and GDNF expression via epigenetic mechanisms.

Unconventional Extraction of Total Non-Polar Carotenoids from Pumpkin Pulp and Their Nanoencapsulation.

Pumpkin is considered a functional food with beneficial effects on human health due to the presence of interesting bioactives. In this research, the impact of unconventional ultrasound-assisted extraction (UAE) and microwave-assisted extraction techniques on the recovery of total non-polar carotenoids from Cucurbita moschata pulp was investigated. A binary (hexane:isopropanol, 60:40 v/v) and a ternary (hexane:acetone:ethanol, 50:25:25 v/v/v) mixture were tested. The extracts were characterized for their antioxidant properties by in vitro assays, while the carotenoid profiling was determined by high-performance liquid chromatography coupled with a diode array detector. UAE with the binary mixture (30 min, 45 °C) was the most successful extracting technique, taking into consideration all analytical data and their correlations. In parallel, solid lipid nanoparticles (SLN) were optimized for the encapsulation of the extract, using ß-carotene as a reference compound. SLN, loaded with up to 1% ß-carotene, had dimensions (~350 nm) compatible with increased intestinal absorption. Additionally, the ABTS ((2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay showed that the technological process did not change the antioxidant capacity of ß-carotene. These SLN will be used to load an even higher percentage of the extract without affecting their dimensions due to its liquid nature and higher miscibility with the lipid with respect to the solid ß-carotene.

Clinical assessment for diet prescription.

Accurate nutritional assessment based on dietary intake, physical activity, genetic makeup, and metabolites is required to prevent from developing and/or to treat people suffering from malnutrition as well as other nutrition related health issues. Nutritional screening ought to be considered as an essential part of clinical assessment for every patient on admission to healthcare setups, as well as on change in clinical conditions. Therefore, a detailed nutritional assessment must be performed every time nutritional imbalances are observed or suspected. In this review we have explored different techniques used for nutritional and physical activity assessment. Dietary Intake (DI) assessment is a multidimensional and complex process. Traditionally, dietary intake is assessed through self-report techniques, but due to limitations like biases, random errors, misestimations, and nutrient databases-linked errors, questions arise about the adequacy of self-reporting dietary intake procedures. Despite the limitations in assessing dietary intake (DI) and physical activity (PA), new methods and improved technologies such as biomarkers analysis, blood tests, genetic assessments, metabolomic analysis, DEXA (Dual-energy X-ray absorptiometry), MRI (Magnetic resonance imaging), and CT (computed tomography) scanning procedures have made much progress in the improvement of these measures. Genes also plays a crucial role in dietary intake and physical activity. Similarly, metabolites are also involved in different nutritional pathways. This is why integrating knowledge about the genetic and metabolic markers along with the latest technologies for dietary intake (DI) and physical activity (PA) assessment holds the key for accurately assessing one's nutritional status and prevent malnutrition and its related complications.

Dietary supplements for lipedema.

Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk.

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa.

Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer.

Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.

LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells.

Glioblastomas (GBs) are among the most common tumors with high malignancy and invasiveness of the central nervous system. Several alterations in protein kinase and ion channel activity are involved to maintain the malignancy. Among them, phosphatidylinositol 3-kinase (PI3K) activity and intermediate conductance calcium-activated potassium (KCa3.1) current are involved in several aspects of GB biology. By using the electrophysiological approach and noise analysis, we observed that KCa3.1 channel activity is LY294002-sensitive and Wortmannin-resistant in accordance with the involvement of PI3K class IIß (PI3KC2ß). This modulation was observed also during the endogenous activation of KCa3.1 current with histamine. The principal action of PI3KC2ß regulation was the reduction of open probability in intracellular free calcium saturating concentration. An explanation based on the "three-gate" model of the KCa3.1 channel by PI3KC2ß was proposed. Based on the roles of KCa3.1 and PI3KC2ß in GB biology, a therapeutic implication was suggested to prevent chemo- and radioresistance mechanisms.

Human breast milk as source of sphingolipids for newborns: comparison with infant formulas and commercial cow's milk.

BACKGROUND: In the past two decades, sphingolipids have become increasingly appreciated as bioactive molecules playing important roles in a wide array of pathophysiology mechanisms. Despite advances in the field, sphingolipids as nutrients remain little explored. Today the research is starting to move towards the study of the sphingomyelin content in human breast milk, recommended for feeding infants. METHODS: In the present study, we performed a lipidomic analysis in human breast milk in relation with maternal diet during pregnancy, in infant formulas, and in commercial whole and semi-skimmed milks for adults. Mediterranean, carnivorous and vegetarian diets were considered. RESULTS: The results showed that total sphingomyelin, ceramide and dihydroceramide species are independent on the diet. Interestingly, the milk sphingolipid composition is species-specific. In fact, infant formulas and commercial milks for adults have a lower level of total sphingomyelin and ceramide content than human breast milk with very different composition of each sphingolipid species. CONCLUSIONS: We conclude that human breast milk is a better source of sphingolipids than infant formulas for baby nutrition with potential implications for the brain development and cognitive functions.

Impact of Goji Berries (Lycium barbarum) Supplementation on the Energy Homeostasis of Rabbit Does: Uni- and Multivariate Approach.

This study examined the effects of goji berries dietary supplementation on the energetic metabolism of doe. Thirty days before artificial insemination, 75 New Zealand White does were assigned to three different diets: commercial standard diet (C) and supplemented with 1% (LG) and 3% (HG) of goji berries, respectively. Body conditions, hormones and metabolites were monitored until weaning. Body weight and BCS were higher in HG than C (p < 0.05). LG showed lower T3/T4 ratio and cortisol concentrations (p < 0.05) and tended to have lower indices of insulin resistances (p < 0.1) than HG. Compared to control, leptin was higher in HG at AI (p < 0.01) and in LG during lactation (p < 0.05). Two principal components were extracted by multivariate analysis describing the relationships between (1) non-esterified fatty acids, insulin and glucose levels, and (2) body conditions and leptin metabolism. The first component highlighted the energy deficit and the insulin resistance of the does during pregnancy and lactation. The second one showed that leptin, body weight and Body Condition Score (BCS) enhance as levels of goji berries in the diet increase. Thus, the effects of goji supplementation are dose-dependent: an improvement on energy metabolism was achieved with a low-dose while the highest dose could determine excessive fattening and insulin resistance in does.

Why Vitamin C Could Be an Excellent Complementary Remedy to Conventional Therapies for Breast Cancer.

The most frequent cancer in women is breast cancer, which is a major cause of death. Currently, there are many pharmacological therapies that have made possible the cure and resolution of this tumor. However, these therapies are accompanied by numerous collateral effects that influence the quality of life (QoL) of the patients to varying degrees. For this reason, attention is turning to the use of complementary medicine to improve QoL. In particular, there are increased trials of intravenous injection of vitamin C at high doses to enhance the antitumor activity of drugs and/or decrease their side effects. This review intends to underline the anticancer mechanisms of vitamin C that could explain its efficacy for treating breast cancer, and why the use of vitamin C at high doses could help patients with breast cancer to enhance the efficacy of pharmacological therapies and/or decrease their side effects.

Pilot study for the evaluation of safety profile of a potential inhibitor of SARS-CoV-2 endocytosis.

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. METHODS: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. RESULTS: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.

Effect of 1α,25(OH)2 Vitamin D3 in Mutant P53 Glioblastoma Cells: Involvement of Neutral Sphingomyelinase1.

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1α,25(OH)2 vitamin D3, a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1α,25(OH)2 vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1α,25(OH)2 vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1α,25(OH)2 vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1α,25(OH)2 vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector.

Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells.

It has been hypothesized that high glucose concentrations might contribute to the overall intracellular oxidative stress either by the direct generation of reactive oxygen species (ROS) or by altering the redox balance. Moreover, it has also been suggested that high glucose concentration can increase the susceptibility of DNA to genotoxic effects of xenobiotics. The aim of this approach was to test high glucose concentrations for pro-genotoxicity in human liver cells by setting up an in vitro model for hyperglycaemia. The experimental design included performing of tests on both human HepG2 tumour cells and HepaRG immortalized cells. Increased cell susceptibility to genotoxic xenobiotics was tested by challenging cell cultures with 4-nitroquinoline-N-oxide (4NQO) and evaluating the extent of primary DNA damage by comet assay. Moreover, we evaluated the relationship between glucose concentration and intracellular ROS, as well as the effects of glucose concentration on the induction of Nrf2-dependent genes such as Glutathione S-transferases, Heme­oxygenase-1, and Glutathione peroxidase-4. To investigate the involvement of ROS in the induced pro-genotoxic activity, parallel experimental sets were set up by considering co-treatment of cells with the model mutagen 4NQO and the antioxidant, glutathione precursor N-acetyl-L-cysteine. High glucose concentrations caused a significant increase in the levels of primary DNA damage, with a pro-genotoxic condition closely related to the concentration of glucose in the culture medium when cells were exposed to 4NQO. High glucose concentrations also stimulated the production of ROS and down-regulated genes involved in contrasting of the effects of oxidative stress. In conclusion, in the presence of high concentrations of glucose, the cells are in unfavourable conditions for the maintenance of genome integrity.

Relationship between Fatty Acids Composition/Antioxidant Potential of Breast Milk and Maternal Diet: Comparison with Infant Formulas.

The fatty acid composition of human breast milk is relevant for the energy, immunity and eicosanoid production in infants. Additionally, the antioxidant properties of foods are essential for human health. Therefore, in the present study we aimed to investigate the relationship between maternal diet and fatty acids composition as well as the antioxidant potential of breast milk from donors to human milk bank of Perugia's hospital, Italy. Results were compared with infant formulas. We observed increased levels of total fatty acids and, in particular, saturated and monounsaturated fatty acids in milk from mothers fed on a vegetable and fruit-rich diet compared with a Mediterranean diet. In the same milk, a reduced antioxidant potential was found. All infant formulas resulted in richer total fatty acid content than human breast milk. Only some formulas were qualitatively similar to breast milk. Of note, the antioxidant potential of the formulas was higher or lower than the human milk with the exception of one sample. The antioxidant potential of four formulas was very high. Dietary supplementation with antioxidants has been shown to have a teratogenic effect and to increase the formation of metastases in adult. There are no data on the effects of excess antioxidants in the infants, but the possibility that they can be harmful cannot be excluded.