Hazelnut Skin Waste as a Functional Ingredient to Nutritionally Improve a Classic Shortbread Cookie Recipe.

Hazelnut skin (HS) is a byproduct of hazelnut processing (2.5% of total kernel) and becomes a food waste despite its high content of antioxidants, unsaturated fats, and fibers. Classic shortbread cookies have a large worldwide market, even if their nutritional composition does not meet nutritional guidelines due to the high content of saturated fats. In the present study, after the nutritional evaluation of four different HS varieties, 5% and 10% ratios of HS of the Tonda Gentile Romana variety were integrated into a classic shortbread cookie recipe, proportionally replacing the butter amount with the unsaturated fats naturally present in HS. The 10% HS addition determined a 20% increase in the monounsaturated oleic acid and a 15.7% decrease in the saturated palmitic acid, in addition to a significant ash increase. The sensory analysis revealed higher consumer acceptance of the 5% formulation, with scores comparable to the control. Although the 10% formulation obtained lower scores for consumer acceptance, 35% of the interviewed population said they would purchase it, indicating that this product, beyond the ethical dimension of using a food waste matrix to promote the circular economy, can attract the commercial interest of part of the population.

Polyphenols as modulators of pre-established gut microbiota dysbiosis: State-of-the-art.

The human intestine contains an intricate ecological community of bacteria, referred as the gut microbiota, which plays a pivotal role in the host homeostasis. Multiple factors could interfere with this delicate balance, thus causing a disruption of the microbiota equilibrium, the so called dysbiosis. Gut microbiota dysbiosis is involved in gastrointestinal and extra-intestinal metabolic diseases, as obesity and diabetes. Polyphenols, present in a broad range of plant foods, are known to have numerous health benefits; however, their beneficial effect on pre-existing dysbiosis is less clear. Indeed, in most of the conducted animal studies the administration of polyphenols or foods rich in polyphenols occurred simultaneously with the induction of the pathology to be examined, then analyzing the preventive action of the polyphenols on the onset of dysbiosis, while very low studies analyzed the modulatory activity of polyphenols on the pre-existing dysbiosis. For this reason, the present review aims to update the current information about the modulation of the pre-established gut microbiota dysbiosis by dietary phenolic compounds in a broad range of disorders in both animal studies and human trials, distinguishing the preventive or treatment approaches in animal studies. The described studies highlight that dietary polyphenols, exerting prebiotic-like effects, can modulate the pre-existing dysbiosis stimulating the growth of beneficial bacteria and inhibiting pathogenic bacteria in both animal models and humans. Anyway, most of the conducted studies are related to obesity and metabolic syndrome, and so further studies are needed to understand this polyphenols' ability in relation to other pathologies.

Effect of malting on nutritional and antioxidant properties of the seeds of two industrial hemp (Cannabis sativa L.) cultivars.

The impact of malting on antioxidant, nutritional, and antinutritional features of two industrial hemp cultivars was investigated. The seeds were steeped (5 h; RT), germinated (3-days; 24 °C), and kilned at different temperatures (6 h; 50 °C or 70 °C). The following determinations were performed on malted and unmalted samples: total phenolic content, polyphenol profile, total antioxidant capacity, tocopherol composition, proximate analysis, fatty acids profile, trypsin inhibitors and phytate content. The results showed that malting increased the protein content up to 9%, without affecting the fat amount, and the fatty acids profile. Total phenolic content, tocopherol profile and total antioxidant capacity were also improved. 70 °C kilning temperature resulted effective to reduce the trypsin inhibitors (up to -27%), increase the reducing power and the level of N-trans-caffeoyltyramine and cannabisin A. Based on this, malting using 3 germination days and 70 °C as kilning temperature could be considered suitable transformation process for improving hempseeds quality.

The Effect of Trans Fatty Acids on Human Health: Regulation and Consumption Patterns.

Health effects of trans fatty acids (TFAs) on human organisms can vary according to their type, structure, composition, and origin. Even though the adverse health effects of industrial TFAs (iTFAs) have been widely discussed, the health effects of natural TFAs (nTFAs) are still questionable. Hence, it is important to review the literature and provide an overall picture on the health effects of different TFAs coming from industrial and ruminant sources, underlining those types that have adverse health effects as well as suggesting methods for reducing their harmful effects. Multiple databases (PubMed, Medline, Cochrane Library, etc.) were searched with the key words "trans fatty acid sources", "ruminant", "industrial", "conjugated trans linoleic acid", "human", "coronary heart disease", "cancer", etc. Reference lists of the studies were scanned discussing the health effects of iTFAs and nTFAs. The review of the literature showed that iTFAs are found to be more harmful than ruminant-produced nTFAs. Although several beneficial effects (such as reduced risk of diabetes) for nTFAs have been observed, they should be used with caution. Since during labeling it is usually not mentioned whether the TFAs contained in food are of industrial or natural origin, the general suggestion is to reduce their consumption.

Detection and Comparison of Bioactive Compounds in Different Extracts of Two Hazelnut Skin Varieties, Tonda Gentile Romana and Tonda Di Giffoni, Using a Metabolomics Approach.

Agro-wastes are one of the major sources for nutritional and therapeutic benefits along with other beneficial properties. Dark brown pellicular pericarp (skin or testa), covering the hazelnut seed, is removed before consumption after the roasting of a kernel. Defatted skins of both hazelnut varieties, Tonda Gentile Romana and Tonda di Giffoni, were profiled by a metabolomics-based approach and this was used to discriminate between these two different hazelnut cultivars. In particular, an untargeted metabolomic extract from hazelnut by-products was investigated by UHPLC-Mass spectrometry followed by multivariate statistics analysis, and significant qualitative and quantitative metabolic differences were observed between them. Samples were also assessed for their total phenolic and antioxidant capacity using two different assays. Although no significant differences were found in total phenolic contents and antioxidant capacity, the Flavone, Flavonol, Flavonoid, and Phenylpropanoid Biosynthesis pathway was significantly higher in the Romana rather than in the Giffoni variety, whereas Myricetin and Syringetin compounds were more representative in Giffoni cultivars. These results indicated that hazelnut skin, especially from the Romana variety, could potentially be used as an ingredient in healthy food. Healthy food is a new food category with an expanding demand from future generations.

Docosahexaenoic Acid Reverted the All-trans Retinoic Acid-Induced Cellular Proliferation of T24 Bladder Cancer Cell Line.

The treatment of solid cancers with pharmacological all-trans retinoic acid (ATRA) concentrations, even if it is a gold standard therapy for the acute promyelocytic leukaemia (APL), is not always effective due to some resistance mechanisms. Here the resistance to ATRA treatment of T24 cell line, bladder cancer, was investigated. T24 was not only resistant to cell death when treated at concentrations up to 20 µM of ATRA, but it was also able to stimulate the cellular proliferation. An over-expression of the fatty acid binding protein 5 (FABP5) in conjunction with the cellular retinol-binding protein-II (CRABP-II) down-expression was found. However, the direct inhibition of the peroxisome proliferator-activated receptor ß/δ (PPARß/δ) did not abolish T24 proliferation, but rather potentiated it. Moreover, considering the ability of the long-chain fatty acids (LCFAs) to displace ATRA from FABP5, the actions of the saturated palmitic acid (PA), unsaturated omega-6 linoleic acid (LA) and omega-3 docosahexaenoic acid (DHA) were evaluated to counteract ATRA-related proliferation. ATRA-PA co-treatment induces cellular growth inhibition, while ATRA-LA co-treatment induces cellular growth enhancement. However, even if DHA is unsaturated LCFA as LA, it was able to reverse the ATRA-induced cellular proliferation of T24, bringing the viability percentages at the levels of the control.

The seed of industrial hemp (Cannabis sativa L.): Nutritional Quality and Potential Functionality for Human Health and Nutrition.

Hempseeds, the edible fruits of the Cannabis sativa L. plant, were initially considered a by-product of the hemp technical fibre industry. Nowadays, following the restorationing of the cultivation of C. sativa L. plants containing an amount of delta-9-tetrahydrocannabinol (THC) <0.3% or 0.2% (industrial hemp) there is a growing interest for the hempseeds production due to their high nutritional value and functional features. The goal of this review is to examine the scientific literature concerning the nutritional and functional properties of hempseeds. Furthermore, we revised the scientific literature regarding the potential use of hempseeds and their derivatives as a dietary supplement for the prevention and treatment of inflammatory and chronic-degenerative diseases on animal models and humans too. In the first part of the work, we provide information regarding the genetic, biochemical, and legislative aspects of this plant that are, in our opinion essential to understand the difference between "industrial" and "drug-type" hemp. In the final part of the review, the employment of hempseeds by the food industry as livestock feed supplement and as ingredient to enrich or fortify daily foods has also revised. Overall, this review intends to encourage further and comprehensive investigations about the adoption of hempseeds in the functional foods field.

Retinoic Acids in the Treatment of Most Lethal Solid Cancers.

Although the use of oral administration of pharmacological all-trans retinoic acid (ATRA) concentration in acute promyelocytic leukaemia (APL) patients was approved for over 20 years and used as standard therapy still to date, the same use in solid cancers is still controversial. In the present review the literature about the top five lethal solid cancers (lung, stomach, liver, breast, and colon cancer), as defined by The Global Cancer Observatory of World Health Organization, and retinoic acids (ATRA, 9-cis retinoic acid, and 13-cis retinoic acid, RA) was compared. The action of retinoic acids in inhibiting the cell proliferation was found in several cell pathways and compartments: from membrane and cytoplasmic signaling, to metabolic enzymes, to gene expression. However, in parallel in the most aggressive phenotypes several escape routes have evolved conferring retinoic acids-resistance. The comparison between different solid cancer types pointed out that for some cancer types several information are still lacking. Moreover, even though some pathways and escape routes are the same between the cancer types, sometimes they can differently respond to retinoic acid therapy, so that generalization cannot be made. Further studies on molecular pathways are needed to perform combinatorial trials that allow overcoming retinoic acids resistance.

Characterization of human breast tissue microbiota from core needle biopsies through the analysis of multi hypervariable 16S-rRNA gene regions.

Breast microbiota compositions are not well understood, and a few recent reports have begun to explore the correlation between breast tissue dysbiosis and cancer. Given that various methods for breast microbiota detection were used, the aim of the present paper was to clarify which hypervariable region of the 16S-rRNA gene (V2, V3, V4, V6 + 7, V8, and V9) is the most informative for breast tissue microbiota. Core needle biopsies (CNBs) were compared with surgical excision biopsies (SEBs) to find a less invasive form of recovery useful for the analysis of a larger statistical population and potentially for diagnostic use of breast tissue microbiota. Finally, this study was the first to analyse the breast microbiota of tumours and paired normal tissues of a Mediterranean population. Our findings showed that the V3 region is the most informative for breast tissue microbiota, accounting for 45% of all reads. No significant differences were found between CNB and SEB specimens in terms of total reads and numbers of Operational Taxonomic Units (OTUs). Moreover, we find that more similarities than differences exist between tumours and adjacent normal tissues. Finally, the presence of the Ralstonia genus is associated with breast tissue.

Impact of Omega-3 Fatty Acids on the Gut Microbiota.

Long-term dietary habits play a crucial role in creating a host-specific gut microbiota community in humans. Despite the many publications about the effects of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined. The few studies completed in adults showed some common changes in the gut microbiota after omega-3 PUFA supplementation. In particular, a decrease in Faecalibacterium, often associated with an increase in the Bacteroidetes and butyrate-producing bacteria belonging to the Lachnospiraceae family, has been observed. Coincidentally, a dysbiosis of these taxa is found in patients with inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by reverting the microbiota composition in these diseases, and increase the production of anti-inflammatory compounds, like short-chain fatty acids. In addition, accumulating evidence in animal model studies indicates that the interplay between gut microbiota, omega-3 fatty acids, and immunity helps to maintain the intestinal wall integrity and interacts with host immune cells. Finally, human and animal studies have highlighted the ability of omega-3 PUFAs to influence the gut-brain axis, acting through gut microbiota composition. From these findings, the importance of the omega-3 connection to the microbiota emerges, encouraging further studies.

Effect of Dietary ω-3 Polyunsaturated Fatty Acid DHA on Glycolytic Enzymes and Warburg Phenotypes in Cancer.

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Among ω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, some in vitro studies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1α functions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.

Pasta containing tartary buckwheat sprouts prevents DNA damage in spontaneously hypertensive rats.

Recent studies have shown that DNA damage occurs more often in hypertensive patients than non-hypertensive individuals. Here, we analyzed the in vivo effect of pasta containing 30% of tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY) to elucidate if TBSP could have an anti-genotoxic effect in hypertensive animal models. Both SHRs and WKY rats were divided into two groups and fed for six weeks with 5 g of TBSP and durum wheat flour commercial pasta, respectively. Our results showed that a diet rich in TBSP has anti-genotoxic effect. Indeed, SHRs fed with TBSP exhibited a significant decrease in DNA damage (38%) and more efficient DNA repair (84%) compared to SHRs fed with commercial pasta.

Development of gluten-free bread using tartary buckwheat and chia flour rich in flavonoids and omega-3 fatty acids as ingredients.

In this study, chia seed flour, which is rich in omega-3 alpha-linolenic acid, and common and tartary buckwheat flour, which has a high antioxidant activity, were integrated into different types of bread with the aim of improving their nutritional value and healthy features. Our results indicate that bread made with chia and tartary buckwheat flour was more acceptable in many nutritional aspects compared to the control (common wheat bread); it contained a higher amount of protein (20%), insoluble dietary fibres (74%), ash (51%), and alpha-linolenic acid (67.4%). Moreover, this bread possessed lower energy (14%) and carbohydrate contents (24%) compared to the control. Tartary buckwheat also improved the total antioxidant capacity of the bread (about 75%) and provided a considerable amount of flavonoids, which are healthy non-nutritional compounds. Overall, chia and tartary buckwheat represent excellent raw materials for the formulation of gluten-free bread with high nutritional value.

A new "functional" pasta containing tartary buckwheat sprouts as an ingredient improves the oxidative status and normalizes some blood pressure parameters in spontaneously hypertensive rats.

Epidemiological studies have reported that some foods, particularly those rich in (poly)phenols, may reduce cardiovascular risk and metabolic disorders such as hypertension. Buckwheat sprouts have been suggested as a new raw material for the production of functional foods due to their high content of healthy compounds such as rutin and quercetin. The aim of this paper is to evaluate the biological hypotensive and antioxidant responses of pasta containing tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHR). In this study, dry tartary buckwheat sprouts were milled to obtain a powder that was used in the production of pasta containing 30% dry buckwheat sprouts and 70% durum wheat semolina. Afterwards, we analyzed the in vitro TBSP features compared with the control (durum wheat flour pasta, DWFP), and the in vivo effects of TBSP on SHR and their normotensive counterpart, Wistar Kyoto rats (WKY rats). The total phenolic content and antioxidant activity were higher in TBSP compared to DWFP. The results showed that SHR fed TBSP exhibited higher plasma levels of the endogenous vasodilators bradykinin (BK) and nitric oxide (NO), a lower level of the vasoconstrictor endothelin-1 (ET-1), and an improved antioxidant capacity. These data suggest that TBSP may help reduce hypertension and oxidative stress in vivo.

Dietary ω -3 polyunsaturated fatty acid DHA: a potential adjuvant in the treatment of cancer.

ω -3 Polyunsaturated fatty acids (PUFAs), mainly present in fish oil, are part of the human diet. Among PUFAs, docosahexaenoic acid (DHA) has received particular attention for its anti-inflammatory, antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties. These data suggest that DHA can exert antitumor activity potentially representing an effective adjuvant in cancer chemotherapy. This review is focused on current knowledge supporting the potential use of DHA for the enhancement of the efficacy of anticancer treatments in relation to its ability to enhance the uptake of anticancer drugs, regulate the oxidative status of tumor cells, and inhibit tumor cell invasion and metastasis.

The n3-polyunsaturated fatty acid docosahexaenoic acid induces immunogenic cell death in human cancer cell lines via pre-apoptotic calreticulin exposure.

Some anticancer chemotherapeutics, such as anthracyclines and oxaliplatin, elicit immunogenic apoptosis, meaning that dying cancer cells are engulfed by dendritic cells and tumor antigens are efficiently presented to CD8+ T cells, which control residual tumor cells. Immunogenic apoptosis is characterized by pre-apoptotic cell surface exposure of calreticulin (CRT), which usually resides into the endoplasmic reticulum. We investigated the ability of the n3-polyunsaturated fatty acid docosahexaenoic acid (22:6n3, DHA) to induce pre-apoptotic CRT exposure on the surface of the human PaCa-44 pancreatic and EJ bladder cancer cell lines. Cells were treated with 150 µM DHA for different time periods, and, by immunoblot and immunofluorescence, we showed that DHA induced CRT exposure, before the apoptosis-associated phosphatidylserine exposure. As for the known immunogenic compounds, CRT exposure was inhibited by the antioxidant GSH, the pan-caspase zVAD-FMK, and caspase-8 IETD-FMK inhibitor. We provide the first evidence that DHA induces CRT exposure, representing thus a novel potential anticancer immunogenic chemotherapeutic agent.

Synthesis of a novel ester of hydroxytyrosol and α-lipoic acid exhibiting an antiproliferative effect on human colon cancer HT-29 cells.

A novel ester of hydroxytyrosol and α-lipoic acid was synthesized in satisfactory yield by original and simple procedures and evaluated about its antiproliferative activity on the human colorectal adenocarcinoma HT-29 cell line. The compound exhibited a cell growth inhibitory activity significantly more potent than the corresponding parent natural compounds, very likely due to the induction of cell cycle arrest in the G2/M phase. These data suggest that the novel ester might exert a more effective antitumour activity than hydroxytyrosol and α-lipoic acid.

Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation.

We investigated the ability of fatty acids to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line and the mechanism(s) underlying apoptosis. Butyric acid, alpha-linoleic acid, and docosahexaenoic acid (DHA) were supplemented at 200 microM concentration in the medium of cell cultures. Our results showed that all fatty acids inhibited cell growth, whereas only DHA induced cell apoptosis. An oxidative process was implicated in apoptosis induced by DHA because butylated hydroxytoluene and vitamin E prevented lipid peroxidation and reversed apoptosis. Intracellular and extracellular glutathione [reduced glutathione (GSH) and oxidized glutathione (GSSG)] concentrations were measured following DHA treatment in the presence or in the absence of GSH extrusion inhibitors such as cystathionine or methionine. DHA induced intracellular GSH depletion without affecting intracellular GSSG concentration and increased extracellular GSH and GSSG levels. Intracellular GSH depletion and extracellular GSH increase were both reversed by cystathionine. Inhibition of active GSH extrusion from the cell by cystathionine or methionine completely reversed lipid peroxidation and apoptosis. These data document the antiproliferative and apoptotic activities of DHA. The date provide evidence that intracellular GSH depletion represents an active extrusion process rather than a consequence of an oxidative stress, suggesting a causative role of GSH depletion in DHA-induced apoptosis.