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1.
Acta Biomater ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992411

ABSTRACT

Collagen-based hydrogels are commonly used in mechanobiology to mimic the extracellular matrix. A quantitative analysis of the influence of collagen concentration and properties on the structure and mechanics of the hydrogels is essential for tailored design adjustments for specific in vitro conditions. We combined focused ion beam scanning electron microscopy and rheology to provide a detailed quantitative atlas of the mechanical and nanoscale three-dimensional structural alterations that occur when manipulating different hydrogel's physicochemistry. Moreover, we study the effects of such alterations on the phenotype of breast cancer cells and their mechanical interactions with the extracellular matrix. Regardless of the microenvironment's pore size, porosity or mechanical properties, cancer cells are able to reach a stable mesenchymal-like morphology. Additionally, employing 3D traction force microscopy, a positive correlation between cellular tractions and ECM mechanics is observed up to a critical threshold, beyond which tractions plateau. This suggests that cancer cells in a stable mesenchymal state calibrate their mechanical interactions with the ECM to keep their migration and invasiveness capacities unaltered. STATEMENT OF SIGNIFICANCE: The paper presents a thorough study on the mechanical microenvironment in breast cancer cells during their interaction with collagen based hydrogels of different compositions. The hydrogels' microstructure were obtained using state-of-the-art 3D microscopy, namely focused ion beam-scanning electron microscope (FIB-SEM). FIB-SEM was originally applied in this work to reconstruct complex fibered collagen microstructures within the nanometer range, to obtain key microarchitectural parameters. The mechanical microenvironment of cells was recovered using Traction Force Microscopy (TFM). The obtained results suggest that cells calibrate tractions such that they depend on mechanical, microstructural and physicochemical characteristics of the hydrogels, hence revealing a steric hindrance. We hypothesize that cancer cells studied in this paper tune their mechanical state to keep their migration and invasiveness capacities unaltered.

2.
Nutr Rev ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38894623

ABSTRACT

Following the goal of optimizing nutrition, the food industry has been continuously working on food reformulation, nutritional patterns, functional foods development, and the general promotion of a healthy lifestyle. To this end, the scientific community has been increasingly investigating natural compounds that could prevent or treat chronic diseases. Phlorotannins and bromophenols are phenolic compounds particularly present in marine organisms. There is extensive evidence that shows their potential in the prevention of noncommunicable diseases, including cancer, the second cause of mortality worldwide. Numerous studies have demonstrated the anticarcinogenic activity of polyphenolic algae compounds both in cell culture and experimental animal models. Although recent reviews are also available, the present update focuses on the most recent findings related to the antioxidant/anti-inflammatory effect of seaweed phenolics, as well as their regulatory capacity for new molecular targets. Additionally, the review addresses and discusses the close link between inflammation and oxidative stress, along with their relationship with tumor onset and progression, including the most recent findings supporting this correlation. Although clinical studies are still needed to support this evidence, phlorotannins and bromophenols constitute an emerging bioactive group with high potential as chemopreventive agents and/or potential adjuvants for existing cancer therapies.

3.
Cancers (Basel) ; 15(23)2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38067247

ABSTRACT

Biliary tract tumours, including bile duct, gallbladder, and ampulla of Vater malignancies, pose a rare but formidable oncologic challenge. Typically diagnosed at advanced stages, these tumours offer limited treatment options and dismal prognoses, with a five-year survival rate below 20%. First-line chemotherapy with gemcitabine-cisplatin has demonstrated only modest efficacy, leaving a pressing need for improved therapeutic strategies. This comprehensive review provides a detailed examination of the current landscape of second-line chemotherapy for biliary tract tumours. The pivotal ABC-06 trial established FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as the standard second-line therapy, demonstrating improved overall survival compared to active symptom control alone. Conversely, the NIFTY trial introduced nal-IRI (nanoliposomal irinotecan) plus 5-FU/LV (5-fluorouracil and leucovorin) as an alternative option, demonstrating substantial gains in progression-free and overall survival. However, the posterior NALIRICC trial presented conflicting results, raising questions about the added benefit of nal-IRI. Challenges in delivering second-line chemotherapy include rapid patient performance deterioration post-first-line treatment and limited access to second-line therapy. Only a fraction of eligible patients receive second-line therapy, emphasising the need for more effective first-line therapies to maintain patient fitness. The role of monotherapy in the second-line setting remains uncertain, particularly in unfit patients, and the absence of biomarkers for tailored treatment underscores the need for ongoing research. While challenges persist, ongoing investigations offer hope for optimising second-line therapy for biliary tract tumours, promising improved outcomes for patients facing this disease. This review provides an overview of current facts and challenges when delivering second-line chemotherapy for advanced biliary tract tumours.

4.
Food Res Int ; 174(Pt 1): 113581, 2023 12.
Article in English | MEDLINE | ID: mdl-37986526

ABSTRACT

The absorption and metabolism of bioactive compounds (BCs) in a Hibiscus sabdariffa drink (HbD) were evaluated by the in vivo bioavailability of organic acids (OA) and phenolic compounds (PC's). An acute single-blind clinical study in humans was conducted. Twelve volunteers consumed a HbD and a control drink (CD). Urine and plasma samples were taken after consuming both beverages. OA and PC's of the beverages (HbD and CD) and the biological samples (urine and plasma) were characterized by HPLC-DAD-MS. Thirthy-eight compounds in HbD and four CD were detected and quantified, equivalent to 937.37 mg and 1.22 mg per 60 mL, respectively. Hibiscus acid was the most abundant OA in both drinks. Additionally, hydroxycinnamic acids, flavonoids, anthocyanins, and anthocyanidins were also detected in HbD, although their amount represented 10% of the total BCs. 25 different metabolites were identified, 15 in urine and 23 in plasma. The microbiota extensively biotransformed PCs and their amount was lower than organic acids, particularly hibiscus acid and hydroxycitric acid. The colonic metabolites derived from PCs and organic acids would be behind the anti-inflammatory bioactivity described for Hibiscus sabdariffa L. (Malvaceae family). However, further studies are necessary to evaluate the metabolites responsible for their anti-inflammatory activity.


Subject(s)
Hibiscus , Plant Extracts , Humans , Anthocyanins/analysis , Anti-Inflammatory Agents/pharmacology , Beverages/analysis , Biological Availability , Single-Blind Method
5.
Future Oncol ; 19(25): 1753-1768, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37650764

ABSTRACT

Locally advanced rectal cancer has traditionally been treated with chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, a new strategy, total neoadjuvant therapy, involves the administration of CRT and neoadjuvant chemotherapy with the aim of eradicating micrometastases earlier and achieving greater control of the disease. The use of total neoadjuvant therapy has shown higher rates of pathological complete response and resectability compared with CRT, including improved survival. Nevertheless, distant relapse is the main cause of morbidity and mortality in locally advanced rectal cancer. To address this, new biomarkers are being developed to predict disease response.


Subject(s)
Neoplasms, Second Primary , Rectal Neoplasms , Humans , Neoadjuvant Therapy , Chemoradiotherapy , Chemotherapy, Adjuvant
6.
Nutrients ; 15(9)2023 May 08.
Article in English | MEDLINE | ID: mdl-37432380

ABSTRACT

Obesity has reached pandemic proportions and has become a major health concern worldwide. Therefore, it is necessary to find new strategies against this condition and its associated comorbidities. Green coffee polyphenols (GCP) and oat beta-glucans (BGs) have proven their hypolipidaemic and hypoglycaemic effects. This study aimed to examine the effects of the long-term consumption of supplements containing GCP, BG or the novel GCP/BG combination on lipid and glucose metabolism biomarkers in overweight/obese subjects who maintained their dietary habits and physical activity, hence addressing the difficulty that this population faces in adapting to lifestyle changes. A randomised, crossover, blind trial was carried out in 29 volunteers who consumed either GCP (300 mg), BG (2.5 g) or GCP/BG (300 mg + 2.5 g) twice a day for 8 weeks. Blood samples were collected, and blood pressure and body composition were measured at the beginning and end of each intervention. Total cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), very low-density lipoprotein (VLDL-C) cholesterol, glycated haemoglobin, fasting glucose, insulin, aspartate transaminase, alanine transaminase and different hormones and adipokines were analysed. Only VLDL-C (p = 0.01) and diastolic blood pressure (p = 0.027) decreased after the intervention, especially with the BG supplement. There were no other significant changes in the analysed biomarkers. In conclusion, the regular intake of GCP, BG and GCP/BG without lifestyle changes is not an efficient strategy to improve lipid and glucose homeostasis in overweight/obese subjects.


Subject(s)
Cardiovascular Diseases , beta-Glucans , Humans , Overweight , Phenols , Coffee , Obesity , Polyphenols , Dietary Supplements , Lipids
7.
Cancers (Basel) ; 15(3)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36765821

ABSTRACT

Colorectal cancer (CRC) is the third most frequent cancer and the second most common cause of cancer-related death in Europe. High microsatellite instability (MSI-H) due to a deficient DNA mismatch repair (dMMR) system can be found in 5% of metastatic CRC (mCRC) and has been established as a biomarker of response to immunotherapy in these tumors. Therefore, immune checkpoint inhibitors (ICIs) in mCRC with these characteristics were evaluated with results showing remarkable response rates and durations of response. The majority of mCRC cases have high levels of DNA mismatch repair proteins (pMMR) with consequent microsatellite stability or low instability (MSS or MSI-low), associated with an inherent resistance to ICIs. This review aims to provide a comprehensive analysis of the possible approaches to overcome the mechanisms of resistance and evaluates potential biomarkers to establish the role of ICIs in pMMR/MSS/MSI-L (MSS) mCRC.

8.
Eur J Nutr ; 62(2): 589-603, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36153442

ABSTRACT

PURPOSE: This study aimed to assess the effect of dietary consumption of olive pomace oil (OPO) on blood lipids (primary outcome) and other cardiovascular disease (CVD) risk factors (blood pressure, inflammation and endothelial function as secondary outcomes). METHODS: A randomized, controlled, blind, crossover intervention was carried out in healthy and at-risk (hypercholesterolemic) subjects. Participants consumed daily 45 g of OPO or high-oleic acid sunflower oil (HOSO) as control oil during 4 weeks. RESULTS: OPO significantly reduced low-density lipoprotein cholesterol (LDL-C; P = 0.003) and apolipoprotein B (Apo B; P = 0.022) serum concentrations, and LDL/HDL ratio (P = 0.027) in healthy and at-risk volunteers. These effects were not observed with HOSO. Blood pressure, peripheral artery tonometry (PAT), endothelial function and inflammation biomarkers were not affected. CONCLUSIONS: Regular consumption of OPO in the diet could have hypolipidemic actions in subjects at cardiovascular risk as well as in healthy consumers, contributing to CVD prevention. CLINICAL TRIAL REGISTRY: NCT04997122, August 8, 2021, retrospectively registered.


Subject(s)
Cardiovascular Diseases , Cholesterol , Humans , Olive Oil , Plant Oils , Sunflower Oil , Oleic Acid , Apolipoproteins B , Cardiovascular Diseases/prevention & control , Inflammation , Cross-Over Studies
9.
Food Chem ; 402: 134472, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36303384

ABSTRACT

An efficient macroporous resin purification process was designed to obtain food-grade phlorotannin-rich extracts from the seaweeds Durvillaea incurvata and Lessonia spicata. Phlorotannins were profiled to relate structures with the α-glucosidase inhibitory activity of the extracts. Liquid chromatography-mass spectrometry was applied for tentative identification. The best phlorotannin purification performance was achieved with HP-20 resin and elution with 80% v/v ethanol. This is the first study that demonstrates the effectivity of HP-20 resin for removing potentially toxic elements (As, Cd) from seaweed extracts. Fucols/phlorethols/fucophlorethols isomers up to 4 phloroglucinol units (PGU) were the most representative phlorotannins. High molecular weight species (11-21 PGU), although in low abundances, were detected in D. incurvata for the first time. Eckols, carmalols, fuhalols, phenolic acids, and flavonoids were also detected. Some extracts' potent α-glucosidase inhibitory activities were related to their high phlorotannin abundances, the presence of phlorotannins of a high degree of polymerization, and the phlorotannins class.


Subject(s)
Phaeophyceae , Seaweed , alpha-Glucosidases , Chromatography, High Pressure Liquid/methods , Tannins/chemistry , Chile , Seaweed/chemistry , Phaeophyceae/chemistry , Phloroglucinol/chemistry , Resins, Plant
10.
Food Chem ; 400: 134046, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36067696

ABSTRACT

Psidium guajava L. and Psidium friedrichsthalianum Nied are part of the Psidium species native to America. Nowadays, it is essential to study the phenolic compound (PC) profile and their changes during digestion and the fractions available for absorption. This study aimed to characterize the PC profile in some Psidium species and their bioaccessibility (BA). Fifty-seven compounds were identified, and forty-six belonged to ten different phenolic classes. PC profiles showed significant differences between the species and the intestinal fraction P. friedrichsthalianum Nied. showed the highest PC content, although it mostly belonged to non-extractable polyphenols. This leads to the lowest BA (37%); P. guajava L. 'Morada' showed the highest (47%). Hydroxycinnamic acids were the most stable PC after gastrointestinal digestion. This study showed relevant differences in the PC content and profile of different Psidium species and changes between the PC in the original matrix and those released in the different stages of gastrointestinal digestion.


Subject(s)
Psidium , Coumaric Acids , Digestion , Phenols , Plant Extracts
11.
Ene ; 17(3): 1-11, 2023. graf
Article in Spanish | IBECS | ID: ibc-231464

ABSTRACT

La preeclampsia aparece entre el 2-10% de las gestaciones a partir de la vigésima semana de gestación y con más frecuencia en el embarazo a término, las medidas más importantes van encaminadas a la prevención. El objetivo de esta revisión bibliográfica es conocer la efectividad de la pauta de alimentación en la prevención y manejo de la preeclampsia. Se han revisado 18 publicaciones recientes de los últimos 5 años. En general, las gestantes suelen experimentar excesiva ganancia ponderal y bajo consumo de los principales minerales. Las grasas mono y poliinsaturadas y granos refinados pueden aumentar el riesgo de preeclampsia. Es necesario la valoración y educación nutricional en la mujer en edad fértil y especialmente en las gestantes con riesgo de preeclampsia. (AU)


Preeclampsia appears between 2-10% of pregnancies from the twentieth week of gestation and more frequently in term pregnancy, the most important measures are aimed at prevention. The objective of this bibliographical review is to know the effectiveness of the feeding regimen in the prevention and management of preeclampsia. 18 recent publications from the last 5 years have been reviewed. In general, pregnant women tend to experience excessive weight gain and low consumption of the main minerals. Monounsaturated and polyunsaturated fats and refined grains may increase the risk of preeclampsia. Nutritional assessment and education is necessary in women of childbearing age and especially in pregnant women at risk of preeclampsia. (AU)


Subject(s)
Humans , Pre-Eclampsia/diagnosis , Pre-Eclampsia/prevention & control , Prenatal Nutrition , Nutrition Therapy , Diet Therapy , Diet, Food, and Nutrition
12.
Molecules ; 27(19)2022 Oct 02.
Article in English | MEDLINE | ID: mdl-36235047

ABSTRACT

Brunfelsia grandiflora is an ancient plant widely used for its promising medicinal properties, although little explored scientifically. Despite being a rich source of phenolic compounds responsible in part for the proven anti-inflammatory activity, its characterization has not been carried out to date. The present work deals with the exhaustive identification and quantification of its phenolic fraction, along with its antioxidant activity. Decoction resulting from the bark as fine powder was filtered and lyophilized, and polyphenols were extracted from the resulting product by aqueous-organic solvents. Seventy-nine polyphenols were identified using LC-MSn. Hydroxycinnamates was the most abundant group of compounds (up to 66.8%), followed by hydroxycoumarins (15.5%), lignans (6.1%), flavonols (5.7%), phenolic simples (3.1), gallates (2.3%), flavanols (0.3%), and flavanones (0.2%). About 64% of the characterized phenols were in their glycosylated forms. The quantification of these phytochemicals by LC-QToF showed that this medicinal plant contained 2014.71 mg of phenolic compounds in 100 g dry matter, which evidences a great antioxidant potency determined by ABTS and DPPH assays. Therefore, Brunfelsia grandiflora represents an important source of polyphenols which supports its therapeutic properties scientifically proven.


Subject(s)
Flavanones , Lignans , Antioxidants/chemistry , Antioxidants/pharmacology , Flavonoids , Flavonols , Phenols , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyphenols/chemistry , Polyphenols/pharmacology , Powders , Solvents/chemistry
13.
Nutrients ; 14(19)2022 Sep 22.
Article in English | MEDLINE | ID: mdl-36235579

ABSTRACT

BACKGROUND: olive pomace oil (OPO) is a nutritionally relevant fat due to its high oleic acid content (C18:1) and the presence of a wide range of minor bioactive components. Although numerous in vitro and preclinical studies have been developed to study some of its characteristic components, the health effect of prolonged OPO consumption is unknown. METHODS: a randomised, blinded, cross-over, controlled clinical trial was carried out in 31 normocholesterolemic and 37 hypercholesterolemic subjects. Participants consumed 45 g/day of OPO or sunflower oil (SO) for 4 weeks, each preceded by a 3-week run-in/wash-out phase with corn oil (CO). RESULTS: regular consumption of OPO and SO had no statistically significant effect on any of the markers related to lipid profile, blood pressure, and endothelial function in both groups, except for eNOS levels, which were close to statistical significance due to the effect of oil (OPO and SO) (p = 0.083). A decrease in visceral fat (p = 0.028) in both groups was observed after OPO intake, accompanied by an increment of leptin (p = 0.017) in the hypercholesterolemic group. CONCLUSION: reducing visceral fat after prolonged OPO intake might contribute to improve cardiometabolic status, with a potentially positive effect on the vascular tone. Further clinical trials are needed to confirm the present results.


Subject(s)
Cardiovascular System , Olive Oil , Cardiovascular Diseases , Corn Oil , Humans , Leptin , Oleic Acid , Plant Oils , Sunflower Oil
14.
Nutrients ; 14(15)2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35956383

ABSTRACT

The pistachio is regarded as a relevant source of biologically active components that, compared to other nuts, possess a healthier nutritional profile with low-fat content composed mainly of monounsaturated fatty acids, a high source of vegetable protein and dietary fibre, remarkable content of minerals, especially potassium, and an excellent source of vitamins, such as vitamins C and E. A rich composition in terms of phytochemicals, such as tocopherols, carotenoids, and, importantly, phenolic compounds, makes pistachio a powerful food to explore its involvement in the prevention of prevalent pathologies. Although pistachio has been less explored than other nuts (walnut, almonds, hazelnut, etc.), many studies provide evidence of its beneficial effects on CVD risk factors beyond the lipid-lowering effect. The present review gathers recent data regarding the most beneficial effects of pistachio on lipid and glucose homeostasis, endothelial function, oxidative stress, and inflammation that essentially convey a protective/preventive effect on the onset of pathological conditions, such as obesity, type 2 diabetes, CVD, and cancer. Likewise, the influence of pistachio consumption on gut microbiota is reviewed with promising results. However, population nut consumption does not meet current intake recommendations due to the extended belief that they are fattening products, their high cost, or teething problems, among the most critical barriers, which would be solved with more research and information.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Pistacia , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Diet , Humans , Lipids/analysis , Nuts/chemistry , Pistacia/chemistry , Vitamins/analysis
15.
Foods ; 11(15)2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35892771

ABSTRACT

Olive pomace oil (OPO) is mainly a source of monounsaturated fat together with a wide variety of bioactive compounds, such as triterpenic acids and dialcohols, squalene, tocopherols, sterols and aliphatic fatty alcohols. To date, two long-term intervention studies have evaluated OPO's health effects in comparison with high oleic sunflower oil (HOSO, study-1) and sunflower oil (SO, study-2) in healthy and cardiovascular risk subjects. The present study integrates the health effects observed with the three oils. Two randomized, blinded, cross-over controlled clinical trials were carried out in 65 normocholesterolemic and 67 moderately hypercholesterolemic subjects. Each study lasted fourteen weeks, with two four-week intervention phases (OPO versus HOSO or SO), each preceded by a three-week run-in or washout period. Regular OPO consumption reduced total cholesterol (p = 0.017) and LDL cholesterol (p = 0.018) levels as well as waist circumference (p = 0.026), and only within the healthy group did malondialdehyde (p = 0.004) levels decrease after OPO intake versus HOSO. Contrarily, after the SO intervention, apolipoprotein (Apo) B (p < 0.001) and Apo B/Apo A ratio (p < 0.001) increased, and to a lower extent Apo B increased with OPO. There were no differences between the study groups. OPO intake may improve cardiometabolic risk, particularly through reducing cholesterol-related parameters and waist circumference in healthy and hypercholesterolemic subjects.

16.
Nutrients ; 14(12)2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35745175

ABSTRACT

Knowledge on the bioavailability of coffee (poly)phenols mostly come from single dose postprandial studies. This study aimed at investigating the effects of regularly consuming a green coffee phenolic extract (GCPE) on the bioavailability and metabolism of (poly)phenols. Volunteers with overweight/obesity consumed a decaffeinated GCPE nutraceutical containing 300 mg hydroxycinnamates twice daily for two months. Plasma and urinary pharmacokinetics, and fecal excretion of phenolic metabolites were characterized by LC-MS-QToF at weeks 0 and 8. Fifty-four metabolites were identified in biological fluids. Regular consumption of the nutraceutical produced certain changes: reduced forms of caffeic, ferulic and coumaric acids in urine or 3-(3'-hydroxypenyl)propanoic, and 3,4-dihydroxybenzoic acids in feces significantly increased (p < 0.05) after 8 weeks; in contrast, coumaroylquinic and dihydrocoumaroylquinic acids in urine decreased (p < 0.05) compared to baseline excretion. The sum of intestinal and colonic metabolites increased after sustained consumption of GCPE, without reaching statistical significance, suggesting a small overall effect on (poly)phenols' bioavailability.


Subject(s)
Coffee , Overweight , Biological Availability , Coffee/metabolism , Dietary Supplements , Humans , Obesity , Phenols/metabolism
17.
Foods ; 11(5)2022 Feb 25.
Article in English | MEDLINE | ID: mdl-35267313

ABSTRACT

Many in vitro and in vivo studies support that green coffee polyphenols (GCP) and beta-glucans (BG) present important hypolipidaemic and hypoglycaemic effects. However, their weight-management/-reducing properties are less clear. Considering that these compounds act on different metabolic pathways, their combination could increase their beneficial health effects. The aim of the present study was to investigate the effects of regularly consuming supplements containing GCP, BG or the novel GCP/BG combination on body composition in overweight/obese subjects without changing their dietary and physical activity habits, hence addressing the difficulty to adapt to lifestyle changes. A randomised, cross-over, blind trial was carried out in 29 volunteers who consumed GCP (300 mg), BG (2.5 g) or GCP/BG (300 mg + 2.5 g) twice a day for 8 weeks. At the beginning and end of each of the interventions, body weight, body mass index, body fat%, intracellular and extracellular water, skinfolds (tricipital, bicipital, subscapularis, suprailiac, leg and thigh) and body circumferences (waist, hip, thigh, calf, branchial) were measured. Along the study, volunteers filled out 72 h dietary records, and physical activity was measured using accelerometers. The results show that dietary intake and physical activity were unchanged throughout the study; however, there were no changes in any of the body composition parameters analysed with any of the food supplements. In conclusion, the regular intake of GCP, BG and GCP/BG, without changes in diet and physical activity, is not an efficient strategy to lose weight or induce other positive changes in body composition, although results should be taken with caution as the study was underpowered.

18.
Eur J Cancer ; 166: 229-239, 2022 05.
Article in English | MEDLINE | ID: mdl-35316750

ABSTRACT

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.


Subject(s)
COVID-19 , Neoplasms , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Neoplasms/therapy , Prospective Studies , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
19.
Food Funct ; 13(3): 1133-1152, 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35018954

ABSTRACT

Nutraceuticals based on plant extracts rich in polyphenols, as well as dietary fibres, are new means to fight overweight/obesity and associated diseases. However, to understand the potential effects of polyphenols on health it is critical to study their bioavailability and metabolic fate. Consumption of a green coffee phenolic extract (GCPE) in combination with oat beta-glucan (BG) could affect the pharmacokinetic profile of the main polyphenols present in coffee (hydroxycinnamates). Moreover, the regular intake of the combination could also induce changes. Nine overweight men and women consumed a novel nutraceutical product containing 300 mg of green coffee hydroxycinnamic acids and 2.5 g of BG twice a day for 8 weeks. A pharmacokinetic study was carried out in blood and urine samples taken before (baseline) and at week 8 after the nutraceutical intervention, collecting samples at different times in a 0-24 h interval. Faecal samples were also obtained at 0 and 24 h after the intake of the nutraceutical at baseline and week 8. Phenolic metabolites were analysed by LC-MS-QToF. Results showed that polyphenols were differentially absorbed and extensively metabolized throughout the gastrointestinal tract. An apparent reduction in the excretion of small intestinal metabolites was accompanied by a tendency to increase colonic metabolites after sustained intake (p = 0.052). In conclusion, continued consumption of the GCPE/BG nutraceutical appears to enhance the absorption of hydroxycinnamates by increasing the colonic bioavailability of their derived metabolites compared to baseline, although the regular intake of the nutraceutical did not modify the metabolite profile in any of the biological samples.


Subject(s)
Coffee/metabolism , Coumaric Acids/metabolism , Overweight/metabolism , Polyphenols/metabolism , beta-Glucans/metabolism , Adolescent , Adult , Biological Availability , Female , Humans , Male , Middle Aged , Obesity/metabolism , Young Adult
20.
Food Funct ; 13(2): 574-586, 2022 Jan 24.
Article in English | MEDLINE | ID: mdl-34919104

ABSTRACT

Obesity and its associated comorbidities are a major public health concern worldwide. Reduced energy intake and increased physical activity interventions have limited success in the long term. Nutraceuticals might be an alternative means to help lose weight and reduce obesity-associated cardiometabolic risk factors without changes in the habitual diet. The objective of the present study was to comparatively evaluate the efficiency of nutraceuticals based on the combination of a decaffeinated green coffee bean extract (GCBE) and two types of oat beta-glucans (BG) with different physiochemical properties on obesity related biomarkers in overweight/obese subjects. A randomized, dose-response, parallel, blind study was carried out in four groups of subjects (n = 15 each) who consumed for 6 weeks, twice a day, a nutraceutical containing 3 g d-1 or 5 g d-1 doses of 35% or 70% BG and a fixed amount of GCBE providing 600 mg d-1 of phenols. 35% BG showed a 10 and 100 times higher molecular weight and viscosity, respectively, compared to 70% BG. Food intake, anthropometry and different cardiometabolic markers were assessed at the beginning and end of the intervention. According to the general model of variance with repeated measure analysis, the intervention caused positive changes in the levels of total cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, haemoglobin A1c, insulin, systolic blood pressure (SBP), total body fat percentage (TBF%), visceral fat percentage, and waist and hip circumferences without differences among the treatments, except for SBP and TBF%. Looking into the rates of change [(end value - beginning value)/beginning value] of these parameters, 5 g - 70% BG was the treatment that lowered TBF% the most. In conclusion, 5 g - 70% BG may be more effective in helping to lose weight and additionally, it produced the least bloating according to participants' subjective perception.


Subject(s)
Avena/chemistry , Coffee/chemistry , Obesity/diet therapy , Plant Extracts , beta-Glucans , Adolescent , Adult , Blood Pressure/drug effects , Comorbidity , Dietary Supplements , Female , Humans , Lipids/blood , Male , Middle Aged , Phenols , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Young Adult , beta-Glucans/administration & dosage , beta-Glucans/pharmacology , beta-Glucans/therapeutic use
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