Anti-inflammatory effect of two pomegranate seed oils obtained by green technologies in Caco-2 cells using the bioaccessible fraction from in vitro gastrointestinal digestion.

Pomegranate seeds contain up to 20% oil with a high content of punicic acid (85%), which is responsible for several biological activities. In this work, two pomegranate oils obtained by a two-step sequential extraction, first with an expeller and then via supercritical CO2 technologies, have been studied in a static gastrointestinal in vitro digestion model to evaluate their bioaccessibility. The micellar phases obtained were evaluated by an in vitro model of intestinal inflammation and Caco-2 cells exposed to the inflammatory mediator lipopolysaccharide (LPS). Inflammatory response was assessed by measuring the production of interleukins IL-6 and IL-8, and tumor necrosis factor α (TNF-α), and by evaluating the monolayer integrity. The results obtained indicate that expeller pomegranate oil (EPO) provides the highest amount of micellar phase (ca. 93%) with free fatty acids and monoacylglycerols as major components. The micellar phase obtained with supercritical CO2 pomegranate oil (SCPO) is ca. 82% with similar lipid composition. Micellar phases of EPO and SCPO showed high stability and adequate particle size. EPO shows an anti-inflammatory response, reducing the production of IL-6, IL-8 and TNF-α in LPS stimulated caco-2 cells and increasing the integrity of the cell monolayer as measured by transepithelial electrical resistance (TEER). In the case of SCPO, the anti-inflammatory effect was only evident for IL-8. The present work demonstrates good digestibility, bioaccessibility and anti-inflammatory response of both EPO and SCPO oils.

Dietary and Physical Activity Habits as Conditioning Factors of Nutritional Status among Children of GENYAL Study.

Excess weight (EW) in children has become a severe public health problem. The present study aimed to describe the main lifestyle characteristics and their possible association with nutritional status in a group of schoolchildren enrolled in the GENYAL study, where 221 children in the first or second grade of primary education (6-9 years old) were included. Anthropometric (BMI and bioimpedance), dietary intake (twice-repeated 24 h food record), and physical activity (twice-repeated 24 h physical activity questionnaire) data were collected. Logistic and linear regressions, with p-values adjusted for multiple tests by Bonferroni's method and with sex and age as covariates, were applied. The prevalence of EW was 19%, 25.4%, and 32.2%, according to Orbegozo Foundation, IOFT, and WHO criteria, respectively. The results showed a significant association between schoolchildren's nutritional status and energy balance, defined as the ratio of estimated energy intake to estimated energy expenditure (%), (ß = -1.49 (-1.9-1.07), p < 0.01) and KIDMED Mediterranean Diet Quality Index score (ß = -0.19 (95% IC -0.38-0), p = 0.04), and between the availability of TV or other technological devices in their room and the child's BMI (ß = 1.15 (95% IC 0.20-2.10), p = 0.017) and their fat mass (ß = 3.28 (95% IC 0.69-5.87), p = 0.013). The number of dairy servings/day had a protective effect against EW (OR = 0.48 (0.29-0.75), p adjusted = 0.05)). Studying lifestyle factors associated with obesity is essential for developing tools and strategies for obesity prevention in children.

Phenolic diterpenes from Rosemary supercritical extract inhibit non-small cell lung cancer lipid metabolism and synergise with therapeutic drugs in the clinic.

Lung cancer is one of the most deadly and common cancers in the world. The molecular features of patient's tumours dictate the different therapeutic decisions, which combines targeted therapy, chemotherapy, and immunotherapy. Altered cellular metabolism is one of the hallmarks of cancer. Tumour cells reprogram their metabolism to adapt to their novel requirements of growth, proliferation, and survival. Together with the Warburg effect, the role of lipid metabolism alterations in cancer development and prognosis has been highlighted. Several lipid related genes have been shown to promote transformation and progression of cancer cells and have been proposed as biomarkers for prognosis. Nevertheless, the exact mechanisms of the regulation of lipid metabolism and the biological consequences in non-small cell lung cancer (NSCLC) have not been elucidated yet. There is an urgent necessity to develop multidisciplinary and complementary strategies to improve NSCLC patients´ well-being and treatment response. Nutrients can directly affect fundamental cellular processes and some diet-derived ingredients, bioactive natural compounds and natural extracts have been shown to inhibit the tumour growth in preclinical and clinical trials. Previously, we described a supercritical extract of rosemary (SFRE) (12 - 16% composition of phenolic diterpenes carnosic acid and carnosol) as a potential antitumoral agent in colon and breast cancer due to its effects on the inhibition of lipid metabolism and DNA synthesis, and in the reduction of resistance to 5-FluoroUracil (5-FU). Herein, we demonstrate SFRE inhibits NSCLC cell bioenergetics identifying several lipid metabolism implicated targets. Moreover, SFRE synergises with standard therapeutic drugs used in the clinic, such as cisplatin, pemetrexed and pembrolizumab to inhibit of cell viability of NSCLC cells. Importantly, the clinical relevance of SFRE as a complement in the treatment of NSCLC patients is suggested based on the results of a pilot clinical trial where SFRE formulated with bioactive lipids (PCT/ES2017/070263) diminishes metabolic and inflammatory targets in peripheral-blood mononuclear cells (PBMC), such as MAPK (p=0.04), NLRP3 (p=0.044), and SREBF1 (p=0.047), which may augment the immune antitumour function. Based on these results, SFRE merits further investigation as a co-adjuvant in the treatment of NSCLC. Clinical trial registration: ClinicalTrials.gov Identifier NCT05080920.

Pomegranate Extract Augments Energy Expenditure Counteracting the Metabolic Stress Associated with High-Fat-Diet-Induced Obesity.

Obesity is associated to a low grade of chronic inflammation leading to metabolic stress, insulin resistance, metabolic syndrome, dislipidemia, cardiovascular disease, and even cancer. A Mediterranean diet has been shown to reduce systemic inflammatory factors, insulin resistance, and metabolic syndrome. In this scenario, precision nutrition may provide complementary approaches to target the metabolic alterations associated to "unhealthy obesity". In a previous work, we described a pomegranate extract (PomE) rich in punicalagines to augment markers of browning and thermogenesis in human differentiated adipocytes and to augment the oxidative respiratory capacity in human differentiated myocytes. Herein, we have conducted a preclinical study of high-fat-diet (HFD)-induced obesity where PomE augments the systemic energy expenditure (EE) contributing to a reduction in the low grade of chronic inflammation and insulin resistance associated to obesity. At the molecular level, PomE promotes browning and thermogenesis in adipose tissue, reducing inflammatory markers and augmenting the reductive potential to control the oxidative stress associated to the HFD. PomE merits further investigation as a complementary approach to alleviate obesity, reducing the low grade of chronic inflammation and metabolic stress.

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases.

COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients.

Small cell lung cancer (SCLC) prognosis is the poorest of all types of lung cancer. Its clinical management remains heterogeneous and therefore, the capability to predict survival would be of great clinical value. Metabolic health (MH) status and lipid metabolism are two relevant factors in cancer prevention and prognosis. Nevertheless, their contributions in SCLC outcome have not yet been analyzed. We analyzed MH status and a transcriptomic panel of lipid metabolism genes in SCLC patients, and we developed a predictive genetic risk score (GRS). MH and two lipid metabolism genes, racemase and perilipin 1, are biomarkers of SCLC survival (HR = 1.99 (CI95%: 1.11-3.61) p = 0.02, HR = 0.36 (CI95%: 0.19-0.67), p = 0.03 and HR = 0.21 (CI95%: 0.09-0.47), respectively). Importantly, a lipid GRS of these genes predict better survival (c-index = 0.691). Finally, in a Cox multivariate regression model, MH, lipid GRS and smoking history are the main predictors of SCLC survival (c-index = 0.702). Our results indicate that the control of MH, lipid gene expression and environmental factors associated with lifestyle is crucial for increased SCLC survival. Here, we propose for the first time, a metabolic precision approach for SCLC patients.

Precision Nutrition to Activate Thermogenesis as a Complementary Approach to Target Obesity and Associated-Metabolic-Disorders.

Obesity is associated to increased incidence and poorer prognosis in multiple cancers, contributing to up to 20% of cancer related deaths. These associations are mainly driven by metabolic and inflammatory changes in the adipose tissue during obesity, which disrupt the physiologic metabolic homeostasis. The association between obesity and hypercholesterolemia, hypertension, cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) is well known. Importantly, the retrospective analysis of more than 1000 epidemiological studies have also shown the positive correlation between the excess of fatness with the risk of cancer. In addition, more important than weight, it is the dysfunctional adipose tissue the main driver of insulin resistance, metabolic syndrome and all cause of mortality and cancer deaths, which also explains why normal weight individuals may behave as "metabolically unhealthy obese" individuals. Adipocytes also have direct effects on tumor cells through paracrine signaling. Downregulation of adiponectin and upregulation of leptin in serum correlate with markers of chronic inflammation, and crown like structures (CLS) associated to the adipose tissue disfunction. Nevertheless, obesity is a preventable risk factor in cancer. Lifestyle interventions might contribute to reduce the adverse effects of obesity. Thus, Mediterranean diet interventional studies have been shown to reduce to circulation inflammatory factors, insulin sensitivity and cardiovascular function, with durable responses of up to 2 years in obese patients. Mediterranean diet supplemented with extra-virgin olive oil reduced the incidence of breast cancer compared with a control diet. Physical activity is another important lifestyle factor which may also contribute to reduced systemic biomarkers of metabolic syndrome associated to obesity. In this scenario, precision nutrition may provide complementary approaches to target the metabolic inflammation associated to "unhealthy obesity". Herein, we first describe the different types of adipose tissue -thermogenic active brown adipose tissue (BAT) versus the energy storing white adipose tissue (WAT). We then move on precision nutrition based strategies, by mean of natural extracts derived from plants and/or diet derived ingredients, which may be useful to normalize the metabolic inflammation associated to "unhealthy obesity". More specifically, we focus on two axis: (1) the activation of thermogenesis in BAT and browning of WAT; (2) and the potential of augmenting the oxidative capacity of muscles to dissipate energy. These strategies may be particularly relevant as complementary approaches to alleviate obesity associated effects on chronic inflammation, immunosuppression, angiogenesis and chemotherapy resistance in cancer. Finally, we summarize main studies where plant derived extracts, mainly, polyphenols and flavonoids, have been applied to increase the energy expenditure.

Saponin-Rich Extracts and Their Acid Hydrolysates Differentially Target Colorectal Cancer Metabolism in the Frame of Precision Nutrition.

Saponins or their aglycone form, sapogenin, have recently gained interest as bioactive agents due to their biological activities, their antitumoral effects being among them. Metabolic reprogramming has been recognized as a hallmark of cancer and, together with the increased aerobic glycolysis and glutaminolysis, the altered lipid metabolism is considered crucial to support cancer initiation and progression. The purpose of this study was to assess and compare the inhibitory effects on colorectal cancer cell lines of saponin-rich extracts from fenugreek and quinoa (FE and QE, respectively) and their hydrolyzed extracts as sapogenin-rich extracts (HFE and HQE, respectively). By mean of the latest technology in the analysis of cell bioenergetics, we demonstrate that FE and HFE diminished mitochondrial oxidative phosphorylation and aerobic glycolysis; meanwhile, quinoa extracts did not show relevant activities. Distinct molecular mechanisms were identified for fenugreek: FE inhibited the expression of TYMS1 and TK1, synergizing with the chemotherapeutic drug 5-fluorouracil (5-FU); meanwhile, HFE inhibited lipid metabolism targets, leading to diminished intracellular lipid content. The relevance of considering the coexisting compounds of the extracts or their hydrolysis transformation as innovative strategies to augment the therapeutic potential of the extracts, and the specific subgroup of patients where each extract would be more beneficial, are discussed in the frame of precision nutrition.

Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer.

Lung cancer is one of the most common cancers, still characterized by high mortality rates. As lipid metabolism contributes to cancer metabolic reprogramming, several lipid metabolism genes are considered prognostic biomarkers of cancer. Statins are a class of lipid-lowering compounds used in treatment of cardiovascular disease that are currently studied for their antitumor effects. However, their exact mechanism of action and specific conditions in which they should be administered remains unclear. Here, we found that simvastatin treatment effectively promoted antiproliferative effects and modulated lipid metabolism-related pathways in non-small cell lung cancer (NSCLC) cells and that the antiproliferative effects of statins were potentiated by overexpression of acyl-CoA synthetase long-chain family member 3 (ACSL3). Moreover, ACSL3 overexpression was associated with worse clinical outcome in patients with high-grade NSCLC. Finally, we found that patients with high expression levels of ACSL3 displayed a clinical benefit of statins treatment. Therefore, our study highlights ACSL3 as a prognostic biomarker for NSCLC, useful to select patients who would obtain a clinical benefit from statin administration.

Valorisation of Grape Stems as a Source of Phenolic Antioxidants by Using a Sustainable Extraction Methodology.

Pressurized liquid extraction with ethanol:water mixtures was proposed for obtaining phenolic antioxidants from grape stems. The optimal extraction conditions were elucidated by using a central composite rotatable design (solvent (X1, 0-100% ethanol:water v/v), temperature (X2, 40-120 °C) and time (X3, 1-11 min)). Response surface methodology determined 30% ethanol:water, 120 °C and 10 min as the optimal extraction conditions regarding total phenolic content (TPC) (185.3 ± 2.9 mg gallic acid/g of extract) and antioxidant activity (3.55 ± 0.21 mmol Trolox/g, 1.22 ± 0.06 mmol Trolox/g and 1.48 ± 0.17 mmol Trolox/g of extract in ABTS, DPPH and ORAC methodologies, respectively). The antioxidant activity was attributed to total polymer procyanidins and flavan-3-ol monomers and oligomers, although other phenolic compound contributions should not be ruled out. Forty-two phenolic compounds were identified in the optimal extract, mainly polymer procyanidins and, to a lesser extent, monomers and oligomers of flavan-3-ols, quercetin-3-O-glucuronide, ε-viniferin, gallic and caftaric acid. Ethyl gallate, ellagic acid, protocatechuic aldehyde, delphinidin-7-O-glucoside and cyanidin-3-O-glucoside were reported for the first time in grape stem extracts. In conclusion, this study highlights the use of this winery side stream as a source of antioxidants within a sustainable food system.

Characterization, antioxidant activity, and inhibitory effect on pancreatic lipase of extracts from the edible insects Acheta domesticus and Tenebrio molitor.

Extracts from the edible insects Acheta domesticus and Tenebrio molitor were obtained by ultrasound-assisted extraction (UAE) and pressurized-liquid extraction (PLE) using ethanol (E) or ethanol:water (E:W). Characterization by GC-MS was performed and total phenolic compounds (TPC), antioxidant activity (DPPH) and pancreatic lipase inhibitory capacity were assayed. Most extracts, mainly ethanolic extracts, predominantly presented lipids as free fatty acids, followed by aminoacids, organic acids, carbohydrates, hydrocarbons and sterols. The UAE-E:W extracts were different, being characterized by organic acids for A. domesticus, or aminoacids for T. molitor. All the extracts exhibited antioxidant activity, which correlated with TPC values, being the E:W extracts the most effective. All the extracts showed inhibitory activity of lipase, although those from T. molitor and extracted by PLE were the most effective. Therefore, bioactive insect extracts can be selectively obtained by advanced methods of extraction, being aqueous ethanol preferred for antioxidant activity and PLE for inhibitory lipase activity.

Precision Nutrition and Cancer Relapse Prevention: A Systematic Literature Review.

Cancer mortality rates are undergoing a global downward trend; however, metastasis and relapse after surgery and adjuvant treatments still correlate with poor prognosis and represent the most significant challenges in the treatment of this disease. Advances in genomics, metabolomics, and proteomics are improving our understanding regarding cancer metabolic diversity, resulting in detailed classifications of tumors and raising the effectiveness of precision medicine. Likewise, the growing knowledge of interactions between nutrients and the expression of certain genes could lead to cancer therapies based on precision nutrition strategies. This review aims to identify the recent advances in the knowledge of the mechanistic role of bioactive phytochemicals in foodstuffs in tumor progression, metastasis, and chemo-resistance in order to assess their potential use in precision nutrition therapies targeting relapse in lung, breast, colon, and prostate cancer, and leukemia. A considerable number of bioactive phytochemicals in foodstuffs were identified in the literature with proven effects modulating tumor growth, progression, and metastasis. In addition, the use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products. This can open the possibility for testing combinations of bioactive phytochemicals with cancer relapse treatments as a potential prevention strategy.

Tolerability and Safety of a Nutritional Supplement with Potential as Adjuvant in Colorectal Cancer Therapy: A Randomized Trial in Healthy Volunteers.

Bioactive supplements display relevant therapeutic properties when properly applied according to validated molecular effects. Our previous research efforts established the basis to develop a dietary supplement based on a Rosmarinus officinalis supercritical extract. This was enriched in phenolic diterpenes (RE) with proven properties against signaling pathways involved in colon tumorigenesis, and shark liver oil rich in alkylglycerols (AKG) as a bioactive lipid vehicle to improve RE bioavailability and synergize with the potential therapeutic action of the extract. Herein, we have investigated the tolerability and safety of the supplement and the biological and molecular effects from an immuno-nutritional perspective. Sixty healthy volunteers participated in a six week, double-blind, randomized parallel pilot study with two study arms: RE-AKG capsules (CR) and control capsules (CC). Mean age (±SD) of volunteers was 28.32 (±11.39) and 27.5 (±9.04) for the control and the study groups, respectively. Safety of the CR product consumption was confirmed by analyzing liver profile, vital constants, and oxidation markers (LDLox in blood and isoprostanes and thromboxanes in urine). The following were monitored: (1) the phenotyping of plasmatic leukocytes and the ex vivo response of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs); (2) expression of genes associated with immune-modulation, inflammation, oxidative stress, lipid metabolism, and tumorigenesis; and (3) the correlation of selected genetic variants (SNPs) with the differential responses among individuals. The lack of adverse effects on liver profile and oxidation markers, together with adequate tolerability and safe immunological adaptations, provide high-quality information for the potential use of CR as co-adjuvant of therapeutic strategies against colorectal cancer.

Protective effect of hydroxytyrosol and rosemary extract in a comparative study of the oxidative stability of Echium oil.

The oxidative stability of Echium oil has been studied by two accelerated oxidation methodologies namely Rancimat and differential scanning calorimetry at selected temperatures in the range 50-110 °C. Kinetic analyses have provided Arrhenius parameters, oxidative stability indexes (OSI), temperature coefficients (tcoef), Q10 and OSI at 20 °C (OSI20) for both methodologies focussing on secondary and tertiary oxidation products. Peroxide, p-anisidine and polar compounds values have been measured to characterize from primary to tertiary oxidation products. In general, susceptibility of this oil to oxidation has been found to be larger than for other vegetable oils, according to the OSI20 values estimated by Rancimat and differential scanning calorimetry. However, the values of tcoeff and Q10 are found to be similar to those described for vegetable oils. In addition, a study of the influence of two antioxidants, namely hydroxytyrosol and rosemary extract on the oxidative stability of Echium oil has been carried out using both methodologies. Protective effects over oxidation by up to a threefold increase of OSI20 values have been found for both antioxidants at the highest dose utilized.

Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.

Metabolic reprogramming is considered a hallmark of cancer. Currently, the altered lipid metabolism in cancer is a topic of interest due to the prominent role of lipids regulating the progression of various types of tumors. Lipids and lipid-derived molecules have been shown to activate growth regulatory pathways and to promote malignancy in pancreatic cancer. In a previous work, we have described the antitumoral properties of Yarrow (Achillea Millefolium) CO2 supercritical extract (Yarrow SFE) in pancreatic cancer. Herein, we aim to investigate the underlaying molecular mechanisms by which Yarrow SFE induces cytotoxicity in pancreatic cancer cells. Yarrow SFE downregulates SREBF1 and downstream molecular targets of this transcription factor, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD). Importantly, we demonstrate the in vivo effect of Yarrow SFE diminishing the tumor growth in a xenograft mouse model of pancreatic cancer. Our data suggest that Yarrow SFE can be proposed as a complementary adjuvant or nutritional supplement in pancreatic cancer therapy.

Yarrow Supercritical Extract Ameliorates the Metabolic Stress in a Model of Obesity Induced by High-Fat Diet.

Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose.

Marigold Supercritical Extract as Potential Co-adjuvant in Pancreatic Cancer: The Energetic Catastrophe Induced via BMP8B Ends Up With Autophagy-Induced Cell Death.

The recent development of powerful "omics" technologies (genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has opened new avenues in nutritional sciences toward precision nutrition, which is a genotype-directed nutrition that takes into account the differential responses to nutritional interventions based on gene variation (nutrigenetics) and the effect of nutrients on gene expression (nutrigenomics). Current evidence demonstrates that up to one third of the deaths caused by cancer could be prevented by acting on key risk factors, with diet being one of the most important risk factors due to its association with obesity. Additional factors such as composition of gut microbiome, the immune system, and the nutritional status will have an impact on the final outcome. Nutrient components and bioactive compounds from natural sources can have an impact on cancer progression or even the risk of cancer development by regulating gene expression and/or associated risk factors such as obesity and chronic inflammation. Nowadays, among the different methods to produce natural extracts, the green technology of supercritical fluid extraction (SFE) is quite popular, with a special interest on the use of supercritical CO2 for the extraction of compounds with low polarity. The success of nutritional interventions based on the use of nutraceuticals requires several steps: (i) in vitro and preclinical demonstration of their antitumoral effects; (ii) knowledge of their mechanism of action and molecular targets, which will allow for identification of the specific subgroups of patients who will benefit from them; (iii) the study of genetic variants associated with the differential responses; and (iv) innovative approaches of formulations to improve the in vivo bioavailability of the bioactive ingredients. Herein, we investigate the antitumoral properties and mechanism of action of a supercritical CO2 extract from Calendula officinalis, commonly known as marigold (marigold SFE) in the context of pancreatic cancer. Mechanistically, marigold SFE induces the expression of BMP8B, which leads to an energetic catastrophe ending up with autophagy-induced cell death (AICD). As metabolic reprogramming is a well-recognized hallmark of cancer, the direct impact of marigold SFE on pancreatic cancer cell metabolism encourages further research of its potential as a coadjuvant in pancreatic cancer therapy. Finally, we discuss innovative formulation approaches to augment the clinical therapeutic potential of marigold SFE in nutritional interventions.

Inhibitory effect of quinoa and fenugreek extracts on pancreatic lipase and α-amylase under in vitro traditional conditions or intestinal simulated conditions.

Ethanol extracts (EE) from fenugreek and quinoa seeds with different total content of inhibitory compounds (TIC, total saponin plus phenolic) were prepared with and without concentration of TIC (CEE -concentrated EE-, and EE, respectively). Their inhibitory activity on pancreatic lipase and α-amylase was assessed by traditional in vitro methods (with or without orbital shaking), and by simulating intestinal digestion. CEE contained higher contents of TIC than EE, being fenugreek superior to quinoa (p < 0.001). The extracts inhibited enzymes in a dose-dependent manner, CEE extracts being stronger (fenugreek for lipase -p = 0.009-, and quinoa for α-amylase -p < 0.001-). Shaking did not impact the activity. Intestinal conditions worsened the inhibition of lipase, but slightly catalyzed the α-amylase. Longer times of reaction worsened activities. The importance of assessing the inhibitory activity of extracts under simulated intestinal conditions is concluded, being fenugreek more interesting than quinoa, especially against pancreatic lipase.

Protein matrices ensure safe and functional delivery of rosmarinic acid from marjoram (Origanum majorana) extracts.

BACKGROUND: To understand the interactions between carriers and functional ingredients is crucial when designing delivery systems, to maximize bioefficacy and functionality. In this study, two different protein matrices were evaluated as means to protect the extract isolated from marjoram leaves (Origanum majorana), casein micelles from fresh skim milk and soy protein isolate (SPI). RESULTS: Marjoram extract was obtained from pressurization of ethanol and water solvent. Protein dispersions of casein and SPI (5 g L-1 each) with or without marjoram extract (0.1-3 mg mL-1 ) were prepared and homogenized. The physicochemical characterization of charge and entrapment efficiency were conducted. The results demonstrated that entrapment efficiency was highly dependent on the carrier itself where SPI formulations showed 20% higher affinity when compared to casein micelles. To investigate the physiological behaviour of the marjoram-protein dispersions, human macrophages were employed. A non-specific inflammatory response of macrophages stimulated with bacterial lipopolysaccharide was measured for TNF-α, IL-1ß and IL-6 cytokine secretion. CONCLUSION: Casein and SPI protein formulations warranted high bioefficacy of marjoram extract, showing their potential as safe carriers. © 2018 Society of Chemical Industry.

Characteristics and determinants of dietary intake and physical activity in a group of patients with multiple chemical sensitivity. / Características y condicionantes de la ingesta dietética y actividad física en un grupo de pacientes diagnosticados de sensibilidad química múltiple.

BACKGROUND AND OBJECTIVE: Multiple chemical sensitivity (MCS) is a complex, acquired, chronic syndrome of multifactorial etiology with multiple symptoms. The aim of the study was to assess the nutritional habits, dietary characteristics and physical activity, as well as their determinants, of a population diagnosed with MCS, which may allow for a more precise approach to nutritional improvement. PATIENTS AND METHOD: A descriptive, cross-sectional study in patients diagnosed with MCS. Information was collected using adapted questionnaires. Data included presence of comorbidities, nutritional (use of supplements, types of diet) and food purchasing habits. Dietary intake, food intolerances, and physical activity were also recorded. RESULTS: The study included of 52 patients (48 female) aged 50.9±10.3 years. Diagnosis of MCS was commonly associated to chronic fatigue syndrome (70.1%), fibromyalgia (65.4%), or electrosensitivity (51.9%). The most common comorbidities were irritable bowel, gastroesophageal reflux, and depression/anxiety-depressive disorder. Exclusion diets were followed by 57.7%, 52.1% commonly used supplements (6.4±5.2 per person), and 16.0% took more than 10 daily. A high proportion of volunteers did not take the recommended amounts of dairy products (84.3%), fruit (82.3%), and cereals (64.7%), the foods to which intolerance was greatest. As regards physical activity, active subjects only represented 12.5%. CONCLUSIONS: The data collected support the need to improve food pattern and to perform physical activity according to individual characteristics. Nutritional education and diet personalization could prevent incomplete, monotonous, and unbalanced diets which impair quality of life and physiological status.