Circadian rhythm and disease: Relationship, new insights, and future perspectives.

The circadian system is responsible for internal functions and regulation of the organism according to environmental cues (zeitgebers). Circadian rhythm dysregulation or chronodisruption has been associated with several diseases, from mental to autoimmune diseases, and with life quality change. Following this, some therapies have been developed to correct circadian misalignments, such as light therapy and chronobiotics. In this manuscript, we describe the circadian-related diseases so far investigated, and studies reporting relevant data on this topic, evidencing this relationship, are included. Despite the actual limitations in published work, there is clear evidence of the correlation between circadian rhythm dysregulation and disease origin/development, and, in this way, clock-related therapies emerge as great progress in the clinical field. Future improvements in such interventions can lead to the development of successful chronotherapy strategies, deeply contributing to enhanced therapeutic outcomes.

The Influence of Circadian Rhythm on Cancer Cells Targeting and Transfection Efficiency of a Polycation-Drug/Gene Delivery Vector.

The conception of novel anticancer delivery systems and the combination of chronobiology with nanotechnology may provide a powerful tool to optimize cancer therapy. In this work, polyethylenimine (PEI) has been used to complex p53 encoded plasmid DNA (pDNA), and the anticancer drug methotrexate (MTX) has also been loaded into the vectors. To investigate the influence of circadian clock on drug/gene delivery efficiency, HeLa, C33A and fibroblast cells have been transfected with developed PEI/pDNA/MTX delivery vectors at six different time points. Phenomena as the cellular uptake/internalization, drug/gene delivery and p53 protein production have been evaluated. The cell-associated MTX fluorescence have been monitored, and p53 protein levels quantified. In HeLa and C33A cancer cells, significant levels of MTX were found for T8 and T12. For these time points, a high amount of p53 protein was quantified. Confocal microscopy images showed successful HeLa cell's uptake of PEI/pDNA/MTX particles, at T8. In comparison, poor levels of MTX and p53 protein were found in fibroblasts; nevertheless, results indicated rhythmicity. Data demonstrate the influence of circadian rhythm on both cancer-cells targeting ability and transfection performance of PEI/pDNA/MTX carriers and seemed to provide the optimum time for drug/gene delivery. This report adds a great contribution to the field of cancer chronobiology, highlighting the relationship between circadian rhythm and nanodelivery systems, and charting the path for further research on a, yet, poorly explored but promising topic.

Exploring the link between chronobiology and drug delivery: effects on cancer therapy.

Circadian clock is an impressive timing system responsible for the control of several metabolic, physiological and behavioural processes. Nowadays, the connection between the circadian clock and cancer occurrence and development is consensual. Therefore, the inclusion of circadian timing into cancer therapy may potentially offer a more effective and less toxic approach. This way, chronotherapy has been shown to improve cancer treatment efficacy. Despite this relevant finding, its clinical application is poorly exploited. The conception of novel anticancer drug delivery systems and the combination of chronobiology with nanotechnology may provide a powerful tool to optimize cancer therapy, instigating the incorporation of the circadian timing into clinical practice towards a more personalized drug delivery. This review focuses on the recent advances in the field of cancer chronobiology, on the link between cancer and the disruption of circadian rhythms and on the promising targeted drug nanodelivery approaches aiming the clinical application of cancer chronotherapy.

Opuntia ficus-indica (L.) Mill.: A Multi-Benefit Potential to Be Exploited.

Consumer interest in foods with enhanced nutritional quality has increased in recent years. The nutritional and bioactive characterization of fruits and their byproducts, as well as their use in the formulation of new food products, is advisable, contributing to decrease the global concerns related to food waste and food security. Moreover, the compounds present in these raw materials and the study of their biological properties can promote health and help to prevent some chronic diseases. Opuntia ficus-indica (L.) Mill. (prickly pear) is a plant that grows wild in the arid and semi-arid regions of the world, being a food source for ones and a potential for others, but not properly valued. This paper carries out an exhaustive review of the scientific literature on the nutritional composition and bioactive compounds of prickly pear and its constituents, as well as its main biological activities and applications. It is a good source of dietary fiber, vitamins and bioactive compounds. Many of its natural compounds have interesting biological activities such as anti-inflammatory, hypoglycemic and antimicrobial. The antioxidant power of prickly pear makes it a good candidate as an ingredient of new food products with fascinating properties for health promotion and/or to be used as natural extracts for food, pharmaceutic or cosmetic applications. In addition, it could be a key player in food security in many arid and semi-arid regions of the world, where there are often no more plants.

Compliance of declared vs. analysed values with EU tolerance limits for mandatory nutrients in prepacked foods.

This study assessed compliance between declared and analysed values on prepacked foods, considering the tolerance limits for salt, fat and saturated fatty acids. Foods were distributed by food categories (e.g. snacks, ready-to-eat meals, potato and potato-products, bakery and pastry products) and a total of 209 products were analysed. Only half of the samples with a declared value ≥1.25 g/100 g were within tolerance limits for salt content. The lowest number of samples outside tolerance limits was observed for fat content; for saturated fatty acids, 27% of the samples were outside of tolerance limits. Only amongst "cereal products" were 100% of products compliant for fat and salt declarations. It is of utmost importance that manufacturers update continuously values declared for prepacked foods, because this information is crucial for consumers and food policy-makers as well as being a legal requirement.

Infusions and decoctions of dehydrated fruits of Actinidia arguta and Actinidia deliciosa: Bioactivity, radical scavenging activity and effects on cells viability.

Actinidia deliciosa and A. arguta fruits (kiwifruit and kiwiberry, respectively) are an excellent source of bioactive compounds. The aim of this paper is to valorize the fruits that are not commercialized (e.g. due to inadequate size or physical damage) in infusions and decoctions. The antioxidant activity, the scavenging activity against reactive species, the phenolic profile and the intestinal effects of infusions and decoctions of dehydrated fruits were evaluated and compared. Decoctions presented the highest antioxidant activity and a good ability to capture HOCl and NO. The phenolic composition of A. arguta present quinic acid, cis-caftaric acid and its derivatives, caffeoyl hexoside, luteolin glucuronide, quercetin derivatives and myristin, while A. deliciosa extracts were characterized by the presence of quinic acid, caffeic acid and its derivatives and caffeoyl hexoside. No adverse effects were observed on Caco-2 and HT29-MTX cells. Kiwiberry decoctions showed to be the best option to keep the fruits benefits.

The phytochemical and bioactivity profiles of wild Calluna vulgaris L. flowers.

The nutritional composition of Calluna vulgaris flowers as well as the phytochemical profile, antioxidant (DPPH and FRAP assays), antimicrobial and cytotoxic (in human immortalized non-tumorigenic keratinocyte and fibroblasts) activities of aqueous, hydroalcoholic and ethanolic extracts were evaluated. A high content of fiber and carbohydrates (75%) and the prevalence of α-tocopherol as vitamer deserves attention. Linolenic (35%), linoleic (27%) and palmitic (21%) acids were the most abundant fatty acids. Qualitative and quantitative analysis by LC-MS and 1NMR indicated high levels of quercetin, kaempferol and myricetin derivatives as well as procyanidins. The hydro-alcoholic extract displayed the highest antioxidant activity and total phenolics (TPC) and flavonoid contents (TFC). No adverse effects on cells were observed until a concentration of 100 µg/mL and a good antimicrobial activity was reported against S. epidermidis and S. aureus with the hydro-alcoholic extract. The data obtained demonstrated that wild plants like heather, although not being a common nutritional reference, can be used in an alimentary base as a source of bioactive compounds, namely antioxidants.

The choroid plexus harbors a circadian oscillator modulated by estrogens.

The suprachiasmatic nucleus (SCN) of the hypothalamus is considered the master circadian oscillator in mammals. However, extra-SCN structures in the brain also display daily rhythms. Recently, we have demonstrated that the choroid plexus (CP) expresses core clock genes that are subjected to circadian regulation in a sex-dependent manner. By using CP explants cultured from female knock-in mice carrying the Period-luciferase transgene, we show that CP exhibits endogenous circadian rhythms of PERIOD2::LUCIFERASE expression. Furthermore, we demonstrate that estrogen declines following ovariectomy modulates the daily rhythm expression of Bmal1, Per1 and Per2 in female rat CP, corroborating data obtained in experiments where rat CP epithelial cell (CPEC) cultures were incubated with 17ß-estradiol (E2). The molecular mechanism underlying these effects was also investigated, and we provide evidence that the estrogen receptor (ER) mediates the response of clock genes to E2. In conclusion, our study proves that the CP harbors a circadian oscillator that is modulated by estrogens and demonstrates that E2 regulation occurs through an estrogen-receptor-dependent mechanism.

Trends in the use of natural antioxidants in active food packaging: a review.

The demand for natural antioxidant active packaging is increasing due to its unquestionable advantages compared with the addition of antioxidants directly to the food. Therefore, the search for antioxidants perceived as natural, namely those that naturally occur in herbs and spices, is a field attracting great interest. In line with this, in the last few years, natural antioxidants such as α-tocopherol, caffeic acid, catechin, quercetin, carvacrol and plant extracts (e.g. rosemary extract) have been incorporated into food packaging. On the other hand, consumers and the food industry are also interested in active biodegradable/compostable packaging and edible films to reduce environmental impact, minimise food loss and minimise contaminants from industrial production and reutilisation by-products. The present review focuses on the natural antioxidants already applied in active food packaging, and it reviews the methods used to determine the oxidation protection effect of antioxidant active films and the methods used to quantify natural antioxidants in food matrices or food simulants. Lastly consumers' demands and industry trends are also addressed.

New nutritional composition data on selected traditional foods consumed in Black Sea Area countries.

BACKGROUND: Traditional foods are an important part of the culture, history, identity and heritage of a region or country and are key elements in dietary patterns. In most countries there is limited information on the nutritional composition of such foods and therefore there is a need to investigate, register and promote traditional foods. One of the aims within the 'Sustainable exploitation of bioactive components from the Black Sea Area traditional foods' (BaSeFood) project is to generate for the first time new data on the nutritional composition of traditional foods from six Black Sea Area countries to promote their sustainable development and exploitation. RESULTS: Thirty-three traditional foods were analysed in an accredited laboratory to determine their nutritional composition, and the data were fully documented. The nutrient content varied widely because of the nature and variety of the analysed foods. The energy content ranged between 4 kcal per 100 g for kvass southern and 900 kcal per 100 g for mustard oil, with the exception of the analysed teas, which did not contribute to energy intake. CONCLUSION: The use of a common methodology for the study of traditional foods will enable countries to further investigate these foods. Moreover, a new nutritional knowledge base of traditional foods from Black Sea Area countries will contribute to promote local biodiversity and sustainable diets by maintaining healthy dietary patterns within local cultures.

Traditional foods from the Black Sea region as a potential source of minerals.

BACKGROUND: In the past few years, minerals have assumed great importance in public health. As a consequence, considerable research has been carried out to better understand their physiological role and the health consequences of mineral-deficient diets, to establish criteria for defining the degree of public health severity of malnutrition, and to develop prevention and control strategies. In most countries, there is limited information on the mineral content of traditional foods, and consequently it is very difficult to estimate mineral intake across these countries. RESULTS: Ten minerals were quantified in 33 traditional foods from Black Sea area countries. Our results indicate a considerable variability among the analysed traditional foods; nevertheless, the most abundant components were sodium (ranging from 40.0 to 619 mg 100 g(-1), for kvass southern and herbal dish, respectively), potassium (varied between 45.5 mg 100 g(-1) for millet ale and 938 mg 100 g(-1) for roasted sunflower seeds), and phosphorus (22.2 mg 100 g(-1) and 681 mg 100 g(-1) for sauerkraut and roasted sunflower seeds, respectively). CONCLUSION: This is the first study that provides validated data on the mineral content for 33 traditional foods from Black Sea area countries, which is important in order to elucidate their role in the dietary pattern of populations and to preserve and promote these foods.

An update on potato crisps contents of moisture, fat, salt and fatty acids (including trans-fatty acids) with special emphasis on new oils/fats used for frying.

Eighteen brands of potato crisps, frequently consumed, were analyzed to establish their nutritional value in relation to salt, fat and fatty acid (FA) composition. The purpose of the present study was to determine moisture, total fat, salt contents and FA profiles (including trans-FAs), and to identify the oil/fat used for frying of the 18 brands of potato crisps. Our results show that salt content ranged from 0.127 to 2.77 g/100 g and total fat content of potato crisps varied between 20.0 and 42.8 g/100 g. With respect to FAs analysis, palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2) were the major FAs found in the analyzed potato crisps. It is clear from our work that nowadays most potato crisps are currently produced using oils with high contents in unsaturated FAs, which can be considered as healthier from a nutritional point of view. Nevertheless, some brands of potato crisps still use palm oil or a blend of palm oil and other fats/oils, which are very rich in saturated FAs.