Obesity-induced changes in lipid mediators persist after weight loss.

BACKGROUND: Obesity induces significant changes in lipid mediators, however, the extent to which these changes persist after weight loss has not been investigated. SUBJECTS/METHODS: We fed C57BL6 mice a high-fat diet to generate obesity and then switched the diet to a lower-fat diet to induce weight loss. We performed a comprehensive metabolic profiling of lipid mediators including oxylipins, endocannabinoids, sphingosines and ceramides in key metabolic tissues (including adipose, liver, muscle and hypothalamus) and plasma. RESULTS: We found that changes induced by obesity were largely reversible in most metabolic tissues but the adipose tissue retained a persistent obese metabolic signature. Prostaglandin signaling was perturbed in the obese state and lasting increases in PGD2, and downstream metabolites 15-deoxy PGJ2 and delta-12-PGJ2 were observed after weight loss. Furthermore expression of the enzyme responsible for PGD2 synthesis (hematopoietic prostaglandin D synthase, HPGDS) was increased in obese adipose tissues and remained high after weight loss. We found that inhibition of HPGDS over the course of 5 days resulted in decreased food intake in mice. Increased HPGDS expression was also observed in human adipose tissues obtained from obese compared with lean individuals. We then measured circulating levels of PGD2 in obese patients before and after weight loss and found that while elevated relative to lean subjects, levels of this metabolite did not decrease after significant weight loss. CONCLUSIONS: These results suggest that lasting changes in lipid mediators induced by obesity, still present after weight loss, may play a role in the biological drive to regain weight.

Bioactive chemical compounds in Eremurus persicus (Joub. & Spach) Boiss. essential oil and their health implications.

The genus Eremurus is native to Eastern Europe and temperate Asia. Particularly, Eremurus persicus (Joub. & Spach) Boiss. is highly valued in traditional foods and medicine. Scientific knowledge about E. persicus chemical composition and bioactivity is required. Therefore, the present study is aimed to determine the volatile composition of E. persicus essential oil (EO) by means of gas chromatography coupled to flame ionization/mass spectrometry detection. Moreover, the antioxidant, antimicrobial, anticancer, and acetylcholinesterase inhibitory activities of the EO were tested. Interestingly, the anti-dermatophyte potency was close to that of the drug griseofulvin, with minimum fungicidal concentration ranging between 0.7 and 4.5% depending on the fungi strain. The EO was also effective against hepatocellular carcinoma (Hep-G2) and breast adenocarcinoma (MCF-7) human cancer cell lines in a concentration (200-1500 ng/mL)-dependent manner, with a decrease of the cell viability up to 65% and 52%, respectively. The E. persicus EO was rich in terpenes and oxygenated terpene derivatives. Individually, limonene (16.25%), geranylgeraniol (15.23%), n-nonanal (9.48%), geranyl acetone (9.12%), benzene acetaldehyde (8.51%), linalool (7.93%), α-pinene (6.89%), and 1,8-cineol (5.22%) were the most abundant volatile compounds and could be chosen as analytical markers of this essential oil. In conclusion, our results suggested that this EO possesses a wide range of bioactive properties that could be useful in nutraceutical, functional foods and cosmeceutical formulations.

Imaging of cellular aging in human retinal blood vessels.

To date two main aging vascular lesions have been reported in elderly human retinas: acellular capillaries and microaneurysms. However, their exact mechanism of formation remains unclear. Using high resolution microscopy techniques we revise cellular alterations observed in aged human retinal vessels, such as lipofuscin accumulation, caveolae malfunction, blood basement membrane disruption and enhanced apoptosis that could trigger the development of these aging vascular lesions. Moreover, we have generated a set of original images comparing retinal vasculature between middle and old aged healthy humans to show in a comprehensive manner the main structural and ultrastructural alterations occurred during age in retinal blood vessels.

Microwave-assisted selective synthesis of mono- and bistriazines with π-conjugated spacers and study of the optoelectronic properties.

A series of mono- and bistriazine derivatives were selectively prepared in high yields using microwave irradiation. Donor substituents were attached on the triazine ring, including pyrazolyl-substituted anilines and o-, m-, and p-phenylenediamine as π-conjugated spacers. This method was used to build σ-π-σ-A-σ-D systems for monotriazines and D-σ-A-σ-π-σ-A-σ-D systems for bistriazines. A study of the optoelectronic properties was performed by UV-vis and fluorescence spectroscopy and cyclic voltammetry. The monotriazines do not show any emission, but the bistriazines are blue emitters and show an interesting solvatochromic effect with large Stokes shifts of more than 10,000 cm(-1) in some cases and quantum yields up to 23%. The optoelectronic properties depend on the conjugation and the position and donor character of the substituents and spacers. Cyclic voltammetry was used to determine the energy levels (HOMO and LUMO) in the bistriazines. An increase in the energy of the HOMO and a decrease in the energy of the LUMO were observed upon extending the conjugation. The title compounds showed interesting properties for use in optoelectronic devices, especially as blue emitters.

Plant-based beverages as milk alternatives? Nutritional and functional approach through food labelling.

Plant-based beverages (PBB) market is largely growing. In this study, 136 beverages made of soy, oat, almond, rice, tigernut, and others (mixtures of various plant materials), from the Spanish market were evaluated through labelling information. Energy value and fat content were intermediate between skimmed and whole cow milk; while fatty acids profile was quite different. Carbohydrate content was usually higher than cow milk, and highly dependent on the addition of sugars. All products provided some dietary fibre. With the exception of soy-based drinks, samples presented lower protein and calcium content than milk (1/3 samples studied were Ca-fortified), and 23% were vitamin D enriched. The claim "No added sugars" was in more than 50% samples. A right labelling and nutritional education of consumers is essential to make adequate choices, since the appearing of many claims is not always indicative of a better-quality product. Plant-based beverages cannot be considered as an alternative to milk, but as a different product, with their own nutritional and functional entity. Their inclusion in a diversified balanced diet can provide interesting functional components, such as soluble fibre or unsaturated fatty acids (mainly soybean and almond drink), which can help improve the health status of the population.

Evaluation of different extraction approaches for the determination of phenolic compounds and their metabolites in plasma by nanoLC-ESI-TOF-MS.

Sample preparation is an important step for the determination of phenolic compounds in biological samples. Different extraction methods have been tested to determine phenolic compounds and their metabolites in plasma by nano-liquid chromatography coupled to electrospray ionisation-time-of-flight mass spectrometry (nanoLC-ESI-TOF-MS). The sample treatment optimisation was performed using commercial foetal bovine serum spiked with representative phenolic standards, namely naringenin, luteolin, verbascoside, apigenin, rutin, syringic acid and catechin. Different protein-precipitation conditions were evaluated as well as enzymatic digestion with trypsin and solid-phase extraction using different phases such as C-18, ABN and ENV+, working at different pH values. The optimum extraction procedure consisted of a previous protein-precipitation step using HCl 200 mmol/L in methanol for 2.5 h at 50 °C followed by a solid-phase extraction using C-18 cartridges at pH 2.5. This procedure was finally applied to the plasma of rats overfed with a phenolic-rich Lippia citriodora extract. These samples were analysed by nanoLC-ESI-TOF-MS, enabling the identification of five compounds previously found in the administered L. citriodora extract and one metabolite.

Pneumatosis intestinalis in a radioactive iodine-refractory metastasic thyroid papillary carcinoma with BRAFV600E mutation treated with dabrafenib-trametinib: a case report.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors. CASE PRESENTATION: A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAFV600E mutation was treated with dabrafenib and trametinib as a compassionate use. After 4 months treatment, positron emission tomography-computed tomography (PET-CT) showed PI. At the time of diagnosis, the patient was asymptomatic without signs of peritonitis. The initial treatment was conservative and no specific treatment for PI was needed. Unfortunately, after dabrafenib-trametinib withdrawal, the patient developed tumor progression with significant clinical worsening. CONCLUSIONS: This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms.

Profiling phenolic compounds in underutilized mango peel by-products from cultivars grown in Spanish subtropical climate over maturation course.

Nutraceutical market has undergone an exponential growth worldwide due to its health link-up. With the purpose of evaluating nutraceutical value, the phenolic composition of underutilized mango peel by-products of three cultivars ('Keitt', 'Kent' and 'Osteen') grown in Spanish subtropical climate was monitored at three maturation stages (green, ripe and overripe). Tracking the total phenol content, mango peels were figured out to have until twenty-seven fold higher than edible fraction. Mango peels comprised a wide range of phenolic compounds such as mono- and di-galloyl compounds, gallotannins, phenolic acids, benzophenones and flavonoids. The influence of both factors, cultivar and maturation degree, on the phenolic composition was the main outcome of the research. 'Keitt' mango peel was revealed as the cultivar with the highest phenolic content mainly due to the great quantities of galloyl glucose, 5-galloylquinic acid, digalloylquinic acid, hexagalloyl glucose and macluring galloyl glucoside detected. Regarding to the effect of maturation degree, green mango peels showed the highest amounts of polyphenols, although this behaviour could be dependent on the mango cultivar. Therefore, mango peels resulted to be a promising and low-cost resource of phenolic compounds to be exploited in food industry, but to enhance the nutraceutical value, factors such as cultivar and maturation degree should be taken into account.

HPLC-DAD-Q-ToF-MS profiling of phenolic compounds from mango (Mangifera indica L.) seed kernel of different cultivars and maturation stages as a preliminary approach to determine functional and nutraceutical value.

Mango seed kernel is a by-product which is usually discarded. However, it has been confirmed in this study that seed kernel exhibits more phenolic compounds with bioactive properties than edible fraction of mango. The influence of factors such as cultivar and maturation degree on the phenolic composition has been studied to evaluate nutraceutical value. The comprehensive analysis of phenolic composition by HPLC-DAD-Q-ToF-MS seed kernel from different cultivars ('Keitt', 'Kent'and 'Osteen') at five maturation stages was conducted. Results evidenced that 'Keitt' samples exhibited higher quantities of iriflophenone glucoside, maclurin C-glucoside, maclurin digalloyl glucoside, mangiferin, 5-galloyl quinic acid and trigalloyl glucose at the first three ripening stages. However, seed kernel from 'Osteen' variety showed higher amounts of hexa- and hepta-gallotannins whose concentrations diminished over the maturation course. Therefore, cultivar and maturation stage factors should be take into account due to their influence on the phenolic composition and subsequently on the nutraceutical value.

Kidney androgen-regulated protein transgenic mice show hypertension and renal alterations mediated by oxidative stress.

BACKGROUND: Kidney androgen-regulated protein (KAP), a proximal tubule androgen-regulated gene, codes for a protein of unknown function. METHODS AND RESULTS: To investigate the consequences of KAP overexpression in kidney, we produced KAP transgenic mice and performed microarray expression analyses in kidneys of control and transgenic males. Downregulation of the androgen-sensitive Cyp4A14 monooxygenase gene in KAP transgenic mice prompted us to analyze blood pressure levels, and we observed that transgenic mice were hypertensive. Inhibition of 20-hydroxyeicosatetraenoic acid synthesis by N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) reduced the increased 20-hydroxyeicosatetraenoic acid levels in urine and normalized arterial pressure in transgenic mice, as did the NADPH oxidase inhibitor apocynin. Increased oxidative stress in transgenic mice was demonstrated by (1) enhanced excretion of urinary markers of oxidative stress, 8-iso-prostaglandin F2alpha, 8-hydroxydeoxyguanosine, and thiobarbituric acid-reacting substances; (2) augmented mitochondrial DNA damage and malondialdehyde levels in kidneys; and (3) diminished catalase and glutathione peroxidase activity in transgenic kidneys. Mice exhibited renal defects that included focal segmental glomerulosclerosis, proteinuria, glycosuria, and fibrosis. CONCLUSIONS: Taken together, these results indicate that KAP expression is critical for cardiovascular-renal homeostasis maintenance and that hypertension is associated with increased oxidative stress. This is the first report showing that overexpression of an androgen-regulated, proximal tubule-specific gene induces hypertension. These observations may shed light on the molecular pathophysiology of gender differences in the prevalence and severity of hypertension and chronic renal disease.

High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a Cistus ladanifer aqueous extract.

INTRODUCTION: Cistus ladanifer is an aromatic shrub that is widespread in the Mediterranean region. The labdanum exudate is used in the fragrance industry and has been characterised. However, there is not enough information about the phenolic content of the raw plant, the aerial part of it being a very rich source of bioactive compounds. OBJECTIVE: Characterisation of the bioactive compounds of the raw plant and its aerial parts. METHODOLOGY: High-performance liquid chromatography with diode array and electrospray ionisation mass spectrometric detection was used to carry out the comprehensive characterisation of a Cistus ladanifer shrub aqueous extract. Two different MS techniques were coupled to HPLC: time-of-flight mass spectrometry and tandem mass spectrometry. RESULTS: Many well-known compounds present in Cistus ladanifer were characterised, such as flavonoids, phenolic acids, ellagitanins, hexahydroxydiphenoyl and derivatives, and other compounds. CONCLUSION: The method described simultaneously separated a wide range of phenolic compounds and the proposed characterisation of the major compounds of this extract was carried out. It is important to highlight that, to our knowledge, this is the first time that a Cistus ladanifer aqueous extract from the raw plant has been characterised.

Pressurized GRAS solvents for the green extraction of phenolic compounds from hibiscus sabdariffa calyces.

An environmental friendly extraction procedure has been tested to extract phenolic compounds from H. sabdariffa calyces using pressurized GRAS solvents. A central composite rotatable design (CCRD) was performed to evaluate the influence of the main operational conditions: temperature (40-200 °C) and solvent composition based on aqueous hidroalcoholic solutions (0-100% ethanol). Phenolic composition of experimental extracts analyzed by HPLC-ESI-QTOF-MS showed that higher temperatures and greater ethanol percentages drove to solvents with lower dielectric constants, which resulted in extracts with major quantities of phenolic compounds. An exception was the extraction of cyanidin-3-sambubioside that could only be quantified in extracts performed at the lowest temperature (40 °C) due to its thermal sensibility. In addition, a RSM was carried out with the aim to maximize the extraction of total phenolic content. To this end, the predicted optimal extraction conditions by RSM were 200 °C and 100% (v/v) of ethanol. Results showed that temperature and ethanol percentage had a significant influence on the extraction of total phenolic compounds (p value < 0.05). The mathematical model pointed out 200 °C of temperature and 100% of ethanol as the optimum conditions to perform the isolation of phenolic compounds by means of pressurized GRAS solvents.

Reversal of age-associated frailty by controlled physical exercise: The pre-clinical and clinical evidences.

Demographic aging is one of the most serious challenges facing our society. Although we live longer, we do not live better because it is considered that approximately 16-20% of our life is spent in late-life morbidity. Older people have the greatest risk of developing frailty increasing the risk of presenting various adverse health events such as low quality of life, disability, hospitalization and even death. Frail men and women over 65 years old have lower muscle quality and muscle mass and higher percentage of body fat than non-frail people of the same age. In this review we will address the main physiological changes in the muscular and nervous system associated to aging. More specifically we will review the changes in muscle mass, quality, and strength relating them with the decrease in capillarization and muscular oxidative capacity as well as with the alterations in protein synthesis in the muscle with aging. The last section of the manuscript will be devoted to the animal models of frailty and the indexes developed to measure frailty in these models. We will finally address the importance of exercise training as an intervention to delay or even reverse frailty.

Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection for the separation of eight tetracyclines in honey samples.

Eight antibiotics, chlortetracycline, demeclocycline, doxycycline, methacycline, minocycline, oxytetracycline, tetracycline and rolitetracycline, were separated and quantified in Spanish honey extracts of different floral origin using a commercial RP-C18 HPLC column and two different on-line detectors (diode array and electrospray time-of-flight mass spectrometry (ESI-TOF-MS) systems). Operating a linear gradient at a flow of 2 ml min(-1) the HPLC separation of the eight antibiotics was obtained within 10 min with good peak symmetry and an acceptable resolution (2.1) for the critical band pair rolitetracycline and oxytetracycline. Values of the numbers of theoretical plates (N) were comprised between 2328 and 19448 while the limits of detection in honey were within 0.02-1.03 microg kg(-1) in the case of UV detection and 0.05-0.76 microg kg(-1) for ESI-TOF-MS detection (operating in negative mode). A recovery study was carried out by preparing some quality control samples at four levels of concentration (10, 25, 50 and 100 microg kg(-1)) and percentages between 72% and 98% were attained.

Giacomo Castelvetro's salads. Anti-HER2 oncogene nutraceuticals since the 17th century?

We are accumulating evidence to suggest that 17(th) century Renaissance foodways -largely based on the old "Mediterranean dietary traditions"- may provide new nutraceutical management strategies against HER2-positive breast cancer disease in the 21st century. Epidemiological and experimental studies begin to support the notion that "The Sacred Law of Salads" (i.e., "raw vegetables... plenty of generous (olive) oil") -originally proposed in 1614 by Giacomo Castelvetro in its book The Fruit, Herbs & Vegetables of Italy- might be considered the first (unintended) example of customised diets for breast cancer prevention based on individual genetic make-up (i.e., nutraceuticals against human breast carcinomas bearing HER2 oncogene amplification/overexpression). First, the so-called salad vegetables dietary pattern (i.e., a high consumption of raw vegetables and olive oil) appears to exert a protective effect mostly confined to the HER2-positive breast cancer subtype, with no significant influence on the occurrence of HER2-negative breast cancers. Second, all the main olive oil constituents (i.e., the omega-9 monounsaturated fatty acid oleic acid and polyphenolic compounds such as the secoiridoid oleuropein or the lignan 1-[+]-acetoxypinoresinol) dramatically reduce HER2 expression and specifically induce apoptotic cell death in cultured HER2- positive breast cancer cells, with marginal effects against HER2-negative cells. Third, an olive oil-rich diet negatively influences experimental mammary tumorigenesis in rats likewise decreasing HER2 expression levels. If early 1600s Castelvetro's salads can be used as dietary protocols capable to protecting women against biologically aggressive HER2-positive breast cancer subtypes is an intriguing prospect that warrants to be evaluated in human pilot studies in the future. Here, at least, we would like to recognise Giacomo Castelvetro as the father of modern nutritional genomics in oncology.

Enhanced and green extraction of bioactive compounds from Lippia citriodora by tailor-made natural deep eutectic solvents.

Natural deep eutectic solvents (NADESs) have been postulated as alternative green solvents for the isolation of valuable bioactive compounds from Lippia citriodora. Thus, 11 different NADESs, based on choline chloride (ChCl) as the hydrogen bond acceptor in combination with different hydrogen bond donors (organic acids, polyalcohols, sugars, and urea) were tested. According to the results obtained, ChCl-lactic acid exhibited the highest extraction yield for iridoids, 7.25 mg g-1, phenylpropanoids, 17.23 mg g-1, and flavonoids, 9.02 mg g-1 being significantly greater than phenylpropanoid and flavonoid yields, 15.63 and 5.43 mg g-1 respectively, extracted with methanol as conventional solvent. Subsequently, in order to optimise the most influential microwave assisted extraction (MAE) parameters, a Box-Behnken design paired with a response surface methodology were implemented. Temperature and water content showed a strong effect on the extraction of polyphenol sub-classes, while the effect of irradiation time was less noticeable on extraction yields. Temperature of 63.68 °C, a water content of 32.19% and a microwave irrdiation time of 17.08 min were the optimum conditions provided by the statistical program. The use of NADESs showed potential to facilitate the design and customisation of green tailor-made solvents which have greater extraction capacity than conventional organic solvents.

Byproduct Generated During the Elaboration Process of Isotonic Beverage as a Natural Source of Bioactive Compounds.

Agro-industrial byproducts are considered good sources of macronutrients and phytochemicals. Fruit and vegetable residues (FVR), obtained after the production of an isotonic beverage, have previously been characterized containing 80% insoluble dietary fibers from total fibers (48.4%), 26% available carbohydrates, 9.5% proteins and 5% lipids. Nevertheless, fruit and vegetables provide phytochemicals which have been related to human health such as phenolic compounds. The loss of specific compounds over the production process is related to their partitioning between fruit and vegetables and byproducts. However, phenolic profile of FVR remains unknown. This work is focused on the evaluation of FVR as a natural source of these bioactive compounds. For this purpose, pressurized liquid extraction (PLE) has been proposed as extraction technique for recovering phenolic compounds from FVR. The experimental variables were temperature and percentage of solvent (ethanol and water). Phenolic compounds extracts were characterized by UPLC-ESI-Q-TOF-MS and a discussion about phenolic and macronutrient interactions was established. Globally, 88 compounds were tentatively identified: phenolic acids (28), flavonoids (32), and other polyphenols (28). The PLE conditions applied yielded different breaking matrix-analyte interactions leading to an increase in the number of compounds. The highest phenolic acids content was achieved with high temperature while lower temperatures were more efficient in extracting flavonoid. By establishing the phenolics profile in food byproducts such as FVR, it is possible to more effectively apply these byproducts as nutraceutical, food or pharmaceutical ingredients. PRACTICAL APPLICATION: Flow diagram of bioactive compounds recovering from isotonic beverage byproduct is proposed using pressurized liquid extraction. The plant-bioactives mechanism relies on fruit and vegetable byproducts changes under different extraction conditions. The obtained extracts can most effectively be applied as nutraceuticals or as ingredients in food or pharmaceutical inputs.

Lipid nanocarriers for the loading of polyphenols - A comprehensive review.

Polyphenols are secondary metabolites found in all vascular plants and constitute a large group of at least 10,000 unique compounds. Particular attention is currently being paid to polyphenols attributed to their beneficial effects in the protection and prevention of several diseases. While their use in food, pharmaceutical and cosmetic industries is largely documented, several environmental conditions (e.g. light, temperature or oxygen) may affect the physicochemical stability of polyphenols, compromising their bioactivity in vivo. To overcome these limitations, the loading of polyphenols into nanoparticles has been proposed aiming at both increasing their bioavailability and reducing eventual side effects. Lipid nanoparticles offer several advantages, namely their biodegradability and low toxicity, with the additional capacity to modify the release profile of loaded drugs. This paper is a review of the recent advances of lipid nanocarriers commonly used for the encapsulation of polyphenols, highlighting their added value to increase bioavailability and bioactivity of this group of compounds as well as their application in several diseases.

A rapid, sensitive screening test for polycyclic aromatic hydrocarbons applied to Antarctic water.

We describe a rapid, sensitive, fluorescence screening test for polycyclic aromatic hydrocarbons in water samples that avoids more costly time-consuming methods. The screening test works by detecting benzo[a]pyrene. It runs without the need for any pre-concentration step, thus rendering it suitable for routine use in water-quality-control laboratories. The test recognizes contaminated samples rapidly (150 s) and inexpensively with a cut-off level of 10 ng l(-1), which is the value that the European Union and World Health Organization (WHO) have laid down in its assessment of the quality of water for human consumption. This was first ascertained by analysing tap and waste-water samples before studying environmental water samples from the Antarctic region. The reliability of the screening test was 2% false positives and 4% false negatives in 200 samples of tap and waste-water. The applicability was confirmed by the fact that the predictions of the screening test coincided exactly with results obtained with gas chromatography-mass spectrometry assays. We also discuss the polluted Antarctic samples and the possible sources of the contamination involved.

Extracellular matrix-inspired assembly of glycosaminoglycan-collagen fibers.

We report on the fabrication of fibers exclusively from the extracellular matrix components by interfacial complexation without using any crosslinking agent. The obtained fibers may have different biomedical applications as they are flexible, and cells adhere and remodel them. Moreover, their stability and thickness can be finely tuned by the sulfation degree of the used glycosaminoglycans.