Maternal Supplementation of Vitamin E or Its Combination with Hydroxytyrosol Increases the Gut Health and Short Chain Fatty Acids of Piglets at Weaning.

An adequate intestinal environment before weaning may contribute to diarrhea predisposition and piglet development. This study evaluates how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from gestation affects the piglet's faecal characteristics, short chain fatty acids (SCFAs), fatty acid profile or intestinal morphology as indicators of gut health; and quantify the contribution of the oxidative status and colostrum/milk composition to the piglet's SCFAs content and intestinal health. Dietary VE increased isobutyric acid (iC4), butyric acid (C4), isovaleric acid (iC5), and ∑SCFAs, whereas HXT increased iC4 and tended to decrease ∑SCFAs of faeces. Piglets from HXT-supplemented sows also tended to have higher faecal C20:4n-6/C20:2 ratio C22:6 proportion and showed lower occludin gene expression in the duodenum. The combination of both antioxidants had a positive effect on iC4 and iC5 levels. Correlation analyses and regression equations indicate that faecal SCFAs were related to oxidative status (mainly plasma VE) and colostrum and milk composition (mainly C20:2, C20:3, C20:4 n-6). This study would confirm the superiority of VE over HXT supplementation to improve intestinal homeostasis, gut health, and, consequently piglet growth.

Different Effect of Vitamin E or Hydroxytyrosol Supplementation to Sow's Diet on Oxidative Status and Performances of Weaned Piglets.

Different feeding strategies are being applied to sows in order to obtain homogeneous piglets' weights and improved health status. This study evaluated how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from day 85 of gestation affected the growth pattern of the piglets and their oxidative status; and quantified what these effects were due to. Dietary VE and HXT improved the oxidative status of sows and piglets. Both VE and HXT modified the growth pattern at birth and performances of the piglets in a different way according to the growing period. Piglets' performances were positively correlated with plasma VE and negatively with plasma malondialdehyde (MDA) of the sow. However, the highest variation in growth patterns was explained by the colostrum composition. Significant linear equations were observed between piglets' performances and colostrum saturated (SAT), n-7 monounsaturated fatty acids (C16:1n-7 and C18:1n-7) and different desaturases indices. This study would confirm that VE supplementation to the sow diet could be more adequate than HXT for the improved development during the first weeks of a piglet's life. The combined administration of both antioxidants would not produce additional positive effects compared to the individual supplementation.

Dietary Vitamin E and/or Hydroxytyrosol Supplementation to Sows during Late Pregnancy and Lactation Modifies the Lipid Composition of Colostrum and Milk.

Modifying the composition of a sow's milk could be a strategy to improve the intestinal health and growth of her piglet during the first weeks of life. This study evaluated how dietary supplementation of vitamin E (VE), hydroxytyrosol (HXT) or VE+HXT given to Iberian sows from late gestation affected the colostrum and milk composition, lipid stability and their relationship with the piglet's oxidative status. Colostrum from VE-supplemented sows had greater C18:1n-7 than non-supplemented sows, whereas HXT increased polyunsaturated (∑PUFAs), ∑n-6 and ∑n-3 fatty acids. In 7-day milk, the main effects were induced by VE supplementation that decreased ∑PUFAs, ∑n-6 and ∑n-3 and increased the Δ-6-desaturase activity. The VE+HXT supplementation resulted in lower desaturase capacity in 20-day milk. Positive correlations were observed between the estimated mean milk energy output and the desaturation capacity of sows. The lowest concentration of malondialdehyde (MDA) in milk was observed in VE-supplemented groups, whereas HXT supplementation increased oxidation. Milk lipid oxidation was negatively correlated with the sow's plasma oxidative status and to a great extent with the oxidative status of piglets after weaning. Maternal VE supplementation produced a more beneficial milk composition to improve the oxidative status of piglets, which could promote gut health and piglet growth during the first weeks, but more research is needed to clarify this.

Biological Activities of Miracle Berry Supercritical Extracts as Metabolic Regulators in Chronic Diseases.

Synsepalum dulcificum (Richardella dulcifica) is a berry fruit from West Africa with the ability to convert the sour taste into a sweet taste, and for this reason, the fruit is also known as the "miracle berry" (MB). The red and bright berry is rich in terpenoids. The fruit's pulp and skin contain mainly phenolic compounds and flavonoids, which correlate with their antioxidant activity. Different polar extracts have been described to inhibit cell proliferation and transformation of cancer cell lines in vitro. In addition, MB has been shown to ameliorate insulin resistance in a preclinical model of diabetes induced by a chow diet enriched in fructose. Herein, we have compared the biological activities of three supercritical extracts obtained from the seed-a subproduct of the fruit-and one supercritical extract obtained from the pulp and the skin of MB. The four extracts have been characterized in terms of total polyphenols content. Moreover, the antioxidant, anti-inflammatory, hypo-lipidemic, and inhibition of colorectal cancer cell bioenergetics have been compared. Non-polar supercritical extracts from the seed are the ones with the highest effects on the inhibition of bioenergetic of colorectal (CRC) cancer cells. At the molecular level, the effects on cell bioenergetics seems to be related to the inhibition of main drivers of the de novo lipogenesis, such as the sterol regulatory element binding transcription factor (SREBF1) and downstream molecular targets fatty acid synthase (FASN) and stearoyl coenzyme desaturase 1 (SCD1). As metabolic reprograming is considered as one of the hallmarks of cancer, natural extracts from plants may provide complementary approaches in the treatment of cancer. Herein, for the first time, supercritical extracts from MB have been obtained, where the seed, a by-product of the fruit, seems to be rich in antitumor bioactive compounds. Based on these results, supercritical extracts from the seed merit further research to be proposed as co-adjuvants in the treatment of cancer.

Inhibitory activity of aromatic plant extracts against dairy-related Clostridium species and their use to prevent the late blowing defect of cheese.

The aim of the present work was the selection of aromatic plant essential oils (EOs) and/or ethanolic extracts (EEs) to prevent the late blowing defect (LBD) of cheese caused by Clostridium spp. EEs resulted more effective than EOs to inhibit dairy-borne Clostridium spp. in vitro. Savory, hyssop, lavender and tarragon EEs, which showed the lowest minimal inhibitory concentration against Clostridium tyrobutyricum, were selected to study the prevention of LBD caused by this bacterium in cheese. Addition of savory and lavender EEs to cheese milk delayed LBD by 2 weeks, but at the end of ripening these cheeses showed similar clostridial vegetative cells counts, spoilage symptoms and propionic, and butyric acids levels than blown control cheese. Tarragon EE, with the highest content in caffeic acid, also delayed LBD by 2 weeks, but it was more effective to inhibit Clostridium, since cheese with tarragon EE showed minor LBD symptoms, lower vegetative cells count and lower concentrations of propionic and butyric acids than the rest of cheeses made with EEs. This fact could be also attributable to the greater number of antimicrobial terpenes (1,8-cineole, 4-terpineol, α-terpineol, isoelemicin, methyl eugenol, and methyl trans-isoeugenol) detected in this cheese. This is the first report on the application of EEs to control C. tyrobutyricum in cheese.

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.

Maternal Supplementation with Polyphenols and Omega-3 Fatty Acids during Pregnancy: Prenatal Effects on Fetal Fatty Acid Composition in the Iberian Pig.

Intrauterine Growth Restriction (IUGR) is a major problem in pig production and different strategies, mainly maternal supplementation with different agents, are currently being studied. The combination of hydroxytyrosol and n3-PUFA seems to be a promising treatment to counteract IUGR, since the combination may help improve n3-PUFA composition and lower the inflammatory status of IUGR piglets. The aim of the present study is to determine the effects of a maternal supplementation, from day 35 to day 100 of pregnancy, with linseed oil and hydroxytyrosol on the fetal FA composition. The results showed higher n3 levels, including eicosapentaenoic and docosahexaenoic FA in the offspring from treated gilts, which showed lower n6-PUFA/n3-PUFA (n6/n3) ratios. Saturated and monounsaturated fatty acids were also affected by treatment, especially in the muscle and brain. Thus, a maternal supplementation with linseed oil and hydroxytyrosol affected the fetal FA tissue composition, which could have implications in pig production due to the improvement of the piglets' health status.

Hypothalamic transcriptome analysis reveals male-specific differences in molecular pathways related to oxidative phosphorylation between Iberian pig genotypes.

The hypothalamus is implicated in controlling feeding and adiposity, besides many other physiological functions, and thus can be of great importance in explaining productive differences between lean and fatty pig breeds. The present study aimed to evaluate the hypothalamic transcriptome of pure Iberian (IBxIB) and Large White x Iberian crossbreds (IBxLW) at 60 days-old, produced in a single maternal environment. Results showed the implication of gender and genotype in the hypothalamic transcriptome, with 51 differentially expressed genes (DEGs) between genotypes and 10 DEGs between genders. Fourteen genotype by sex interactions were found, due to a higher genotype effect on transcriptome found in males. In fact, just 31 DEGs were identified when using only females but 158 using only males. A higher expression of genes related to mitochondrial activity in IBxIB male animals (ND3, ND4, ND5, UQCRC2 and ATP6) was found, which was related to a higher oxidative phosphorylation and greater reactive oxygen species and nitric oxide production. IBxLW male animals showed higher expression of SIRT3 regulator, also related to mitochondrial function. When females were analysed, such differences were not found, since only some differences in genes related to the tricarboxylic acid cycle. Thus, the results indicate a significant effect and interaction of the breed and the sex on the hypothalamic transcriptome at this early age.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

Bioactive phenolic compounds and organic acids in the decoction of fruits and leaves of Schinus areira L / Compuestos fenólicos bioactivos y ácidos orgánicos en la decocción de frutos y hojas de Schinus areira L

Leaf and fruit decoctions of Schinus areira L. from northwest Argentina were investigated here. Phenolic compounds and organic acids were analyzed by HPLC. Antioxidant capacity and α-glucosidase inhibition were determined by using in vitro tests. The general toxicity was assessed against Artemia salina nauplii. Hyperoside and 3 O-caffeoylquinic acid in leaf decoctions; gallic acid and catechin in fruit decoction were the major phenolic compounds. Malic and citric acids were the main organic acid quantified in the leaf and fruit decoctions, respectively. Fruit decoction had a relatively important content of shikimic acid, precursor of Tamiflu. Leaf decoction presents a greater richness in bioactive compounds with antiradical activity against DPPH●, O2●-and ●NO radicals. S. areira leaves and fruits had α-glucosidase inhibitory activity comparable to hyperoside and acarbose. Fruit decoction was not eco-toxic; leaf decoction showed significant eco-toxic activity and could be chosen for the search of other bioactive compounds with pharmacological activity.

Se investigaron decocciones de hojas y frutos de Schinus areira L. del noroeste de Argentina. Compuestos fenólicos y ácidos orgánicos se analizaron mediante HPLC. Capacidad antioxidante e inhibición de α-glucosidasa se determinaron in vitro. Se evaluó toxicidad general con Artemia salina. Los principales compuestos fenólicos fueron hiperósido y ácido 3 O-cafeoilquínico en hojas y ácido gálico y catequina en frutos. Los principales ácidos orgánicos cuantificados fueron málico en hojas y cítrico en frutos. Ácido shikímico, precursor del Tamiflu está presente en decocción de frutos con un contenido relativamente importante. La de hojas presenta una mayor riqueza en compuestos bioactivos con actividad antirradicalaria frente a DPPH●, O2●-y ●NO. Las hojas y frutos de S. areira tenían una actividad inhibidora de la α-glucosidasa comparable a la de hiperósido y acarbosa. La decocción de frutas no fue eco-tóxica, pero sí la de hojas que podría ser fuente de compuestos bioactivos con actividad farmacológica.

Maternal Supplementation with Polyphenols and Omega-3 Fatty Acids during Pregnancy: Prenatal Effects on Growth and Metabolism.

Maternal supplementation with antioxidants and n-3 PUFAs may be a promising strategy to reduce the risk of intrauterine growth restriction and preterm delivery, which may diminish the appearance of low-birth-neonates. A previous studies showed beneficial outcomes of the combination of hydroxytyrosol and linoleic acid, but there is no data of its prenatal effects. The present study aimed to determine the possible prenatal implications of such maternal supplementation at prenatal stages in swine, a model of IUGR pregnancies. Results showed effects on litter size, with treated sows having larger litters and, therefore, smaller fetuses. However, the brain/head weight ratio showed a positive effect of the treatment in development, as well as in some other major organs like lungs, spleen, or kidneys. On the other hand, treated piglets showed better glycemic and lipidemic profiles, which could explain postnatal effects. However, further research on the implications of the treatment on litter size and prenatal and postnatal development must be done before practical recommendation can be given.

Effects of L-Glutamine Supplementation during the Gestation of Gilts and Sows on the Offspring Development in a Traditional Swine Breed.

The use of amino acids during pregnancy, such as glutamine (Gln), seems to be a promising strategy in selected swine breeds to improve the offspring prenatal development. The main goal of the current study was to assess the development of the offspring from parity 1-3 sows of a traditional breed, which were supplemented with 1% glutamine after Day 35 of gestation, under farm conditions. A total of 486 (288 treated) piglets from 78 (46 treated) Iberian sows were used. At birth and slaughterhouse, fatty acid composition, metabolism, and mTOR pathway gene expression were analyzed. At birth, treated newborns showed greater amounts of specific amino acids in plasma, such as glutamine, asparagine, or alanine, and Σn-3 fatty acids in cellular membranes than control newborns. The expression of genes belonging to mTOR Complex 1 was also higher in treated piglets with normal birth-weight. However, these findings did not improve productive traits at birth or following periods in litters from supplemented gilts (parity 1) or sows (parities 2-3). Thus, further research is needed to properly understand the effects of prenatal glutamine supplementation, particularly in traditional swine breeds.

Natural Extracts to Augment Energy Expenditure as a Complementary Approach to Tackle Obesity and Associated Metabolic Alterations.

Obesity is the epidemic of the 21st century. In developing countries, the prevalence of obesity continues to rise, and obesity is occurring at younger ages. Obesity and associated metabolic stress disrupt the whole-body physiology. Adipocytes are critical components of the systemic metabolic control, functioning as an endocrine organ. The enlarged adipocytes during obesity recruit macrophages promoting chronic inflammation and insulin resistance. Together with the genetic susceptibility (single nucleotide polymorphisms, SNP) and metabolic alterations at the molecular level, it has been highlighted that key modifiable risk factors, such as those related to lifestyle, contribute to the development of obesity. In this scenario, urgent therapeutic options are needed, including not only pharmacotherapy but also nutrients, bioactive compounds, and natural extracts to reverse the metabolic alterations associated with obesity. Herein, we first summarize the main targetable processes to tackle obesity, including activation of thermogenesis in brown adipose tissue (BAT) and in white adipose tissue (WAT-browning), and the promotion of energy expenditure and/or fatty acid oxidation (FAO) in muscles. Then, we perform a screening of 20 natural extracts (EFSA approved) to determine their potential in the activation of FAO and/or thermogenesis, as well as the increase in respiratory capacity. By means of innovative technologies, such as the study of their effects on cell bioenergetics (Seahorse bioanalyzer), we end up with the selection of four extracts with potential application to ameliorate the deleterious effects of obesity and the chronic associated inflammation.

Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. RESULTS: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. CONCLUSIONS: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Maternal Supplementation with Polyphenols and Omega-3 Fatty Acids during Pregnancy: Effects on Growth, Metabolism, and Body Composition of the Offspring.

Maternal supplementation with antioxidants and n3 PUFAs may be a promising strategy to reduce the risk of intrauterine growth restriction and preterm delivery, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine benefits and risks of a dietary supplementation combining hydroxytyrosol, a polyphenol from olive leaves and fruits, and n3 PUFAs, from linseed oil, on developmental patterns and metabolic traits of offspring in swine, a model of IUGR pregnancies. The results obtained indicate that maternal supplementation with hydroxytyrosol and n-3 fatty acids during pregnancy has no deleterious effects on the reproductive traits of the sows (prolificacy, homogeneity of the litter, and percentage of stillborns and low-birth-weight, LBW, piglets) and the postnatal features of the piglets (growth patterns, adiposity, and metabolic traits). Conversely, in spite of a lower mean weight and corpulence at birth, piglets from the supplemented sows showed higher average daily weight gain and fractional growth rate. Thus, at juvenile stages afterwards, the offspring from the treated group reached higher weight and corpulence, with increased muscle development and better lipidemic and fatty acid profiles, in spite of similar adiposity, than offspring in the control group. However, much caution and more research are still needed before practical recommendation and use in human pregnancies.

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.

Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Hepatic Fat Accretion and Energy and Fatty Acids Profile of Fetal Tissues.

Maternal supplementation with hydroxytyrosol, a polyphenol present in olive leaves and fruits, is a highly promising strategy to improve the oxidative and metabolic status of fetuses at risk of intrauterine growth restriction, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine whether hydroxytyrosol, by preventing lipid peroxidation, may influence the fat accretion and energy homeostasis in the liver, as well as the fatty acid composition in the liver and muscle. The results indicate that hydroxytyrosol treatment significantly decreased the energy content of the fetal liver, without affecting fat accretion, and caused significant changes in the availability of fatty acids. There were significant increases in the amount of total polyunsaturated fatty acids, omega-3 and omega-6, which are highly important for adequate fetal tissue development. However, there were increases in the omega-6/omega-3 ratio and the desaturation index, which make further studies necessary to determine possible effects on the pro/anti-inflammatory status of the fetuses.

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.

Efficacy of vitamin D supplementation in gestational diabetes mellitus: Systematic review and meta-analysis of randomized trials.

BACKGROUND: Trials have examined on the benefits of vitamin D supplementation in pregnant women. OBJECTIVE: This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo. METHOD: We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality. CONCLUSION: We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women.

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.