Pathogen reduction with methylene blue does not have an impact on the clinical effectiveness of COVID-19 convalescent plasma.

BACKGROUND AND OBJECTIVES: There is a concern about a possible deleterious effect of pathogen reduction (PR) with methylene blue (MB) on the function of immunoglobulins of COVID-19 convalescent plasma (CCP). We have evaluated whether MB-treated CCP is associated with a poorer clinical response compared to other inactivation systems at the ConPlas-19 clinical trial. MATERIALS AND METHODS: This was an ad hoc sub-study of the ConPlas-19 clinical trial comparing the proportion of patients transfused with MB-treated CCP who had a worsening of respiration versus those treated with amotosalen (AM) or riboflavin (RB). RESULTS: One-hundred and seventy-five inpatients with SARS-CoV-2 pneumonia were transfused with a single CCP unit. The inactivation system of the CCP units transfused was MB in 90 patients (51.4%), RB in 60 (34.3%) and AM in 25 (14.3%). Five out of 90 patients (5.6%) transfused with MB-treated CCP had worsening respiration compared to 9 out of 85 patients (10.6%) treated with alternative PR methods (p = 0.220). Of note, MB showed a trend towards a lower rate of respiratory progressions at 28 days (risk ratio, 0.52; 95% confidence interval, 0.18-1.50). CONCLUSION: Our data suggest that MB-treated CCP does not provide a worse clinical outcome compared to the other PR methods for the treatment of COVID-19.

Enhancing the Gastrointestinal Stability of Curcumin by Using Sodium Alginate-Based Nanoemulsions Containing Natural Emulsifiers.

Curcumin presents interesting biological activities but low chemical stability, so it has been incorporated into different emulsion-based systems in order to increase its bioaccessibility. Many strategies are being investigated to increase the stability of these systems. Among them, the use of polysaccharides has been seen to highly improve the emulsion stability but also to modulate their digestibility and the release of the encapsulated compounds. However, the effect of these polysaccharides on nanoemulsions depends on the presence of other components. Then, this work aimed to study the effect of alginate addition at different concentrations (0-1.5%) on the gastrointestinal fate and stability of curcumin-loaded nanoemulsions formulated using soybean lecithin or whey protein as emulsifiers. Results showed that, in the absence of polysaccharides, whey protein was more effective than lecithin in preventing curcumin degradation during digestion and its use also provided greater lipid digestibility and higher curcumin bioaccessibility. The addition of alginate, especially at ≥1%, greatly prevented curcumin degradation during digestion up to 23% and improved the stability of nanoemulsions over time. However, it reduced lipid digestibility and curcumin bioaccessibility. Our results provide relevant information on the use of alginate on different emulsifier-based nanoemulsions to act as carriers of curcumin.

The views of women and pharmacists on the desirability of a progestogen-only pill over the counter. Results of a survey in Germany, Italy and Spain.

PURPOSE: To explore the perceived need and enthusiasm for over the counter (OTC) progestogen-only pills (POP). MATERIALS AND METHODS: A web-based survey of 1000 sexually active women (16-45) and 100 pharmacists in Germany, Italy and Spain. RESULTS: Despite not wanting to conceive, 5-6% of women in each country were not using contraception and 8-20% were using methods less effective than condoms. At least 74% of respondents felt knowledgeable about the different contraceptives available but at least 1/3 had experienced difficulty accessing oral contraceptive (OCs) in the past two years. The cost of contraceptives, the need to see a doctor and long waits for appointments were cited as barriers for not using OCs. The majority agreed they would discuss with their doctor the decision to buy the POP, consult about side effects and other reproductive health issues. Over 2/3 of pharmacists in each country would be very, or fairly, likely to recommend the POP, agreeing that the benefits included improved access for women, and offered them more independence. CONCLUSIONS: Asked directly, women in Germany, Spain and Italy currently using contraception are positive about a POP OTC. Pharmacists are also positive, with the overwhelming majority in favour of providing POPs.

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy.

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.

Documentation and incidence of late effects and screening recommendations for adolescent and young adult head and neck cancer survivors treated with radiotherapy.

PURPOSE: A retrospective review of adolescent and young adult (AYA) head and neck cancer (HNC) patients treated with radiation therapy (RT) at British Columbia Cancer  was performed to determine the incidence of late toxicities, the documented late side effects discussed and the screening recommendations provided at the time of transfer of care to primary care providers (PCPs). METHODS: Charts (n = 162) were reviewed for all patients 15 to 35 years at diagnosis with HNC treated with RT from 1960 to 2010 who survived > 5 years after diagnosis. RESULTS: A discussion regarding the risk of long-term side effects was documented in the initial consultation for 85% of patients. The majority of patients (78%) developed > 1 documented late effect. The most common were xerostomia (44%), skin changes (28%), neck fibrosis (22%), nasal crusting (16%), epistaxis (16%), and dental decay (14%). In all, 20% were currently followed or were followed until they died. Of the 80% transferred to their PCP, 14% had a formal discharge summary. For those discharged from British Columbia Cancer, documented recommendations included regular dental care (34%) and screening for hypothyroidism (5%) and second malignancy (4%). CONCLUSIONS: The majority of AYA HNC patients treated with RT developed late side effects, and most PCPs were not sent a discharge summary outlining screening recommendations for delayed late effects. IMPLICATIONS FOR CANCER SURVIVORS: AYA HNC survivors treated with RT are at high risk for late effects and would benefit from a survivorship care plan outlining these risks and screening recommendations.

Maternal mutations of FOXF1 cause alveolar capillary dysplasia despite not being imprinted.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare cause of pulmonary hypertension in newborns. Maternally inherited point mutations in Forkhead Box F1 gene (FOXF1), deletions of the gene, or its long-range enhancers on the maternal allele are responsible for this neonatal lethal disorder. Here, we describe monozygotic twins and one full-term newborn with ACD and gastrointestinal malformations caused by de novo mutations of FOXF1 on the maternal-inherited alleles. Since this parental transmission is consistent with genomic imprinting, the parent-of-origin specific monoallelic expression of genes, we have undertaken a detailed analysis of both allelic expression and DNA methylation. FOXF1 and its neighboring gene FENDRR were both biallelically expressed in a wide range of fetal tissues, including lung and intestine. Furthermore, detailed methylation screening within the 16q24.1 regions failed to identify regions of allelic methylation, suggesting that disrupted imprinting is not responsible for ACDMPV.

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma.

Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage-inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2-FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients.

Integrin-linked kinase regulates tubular aquaporin-2 content and intracellular location: a link between the extracellular matrix and water reabsorption.

One of the clinical alterations observed in chronic renal disease (CRD) is the impaired urine concentration, known as diabetes insipidus (DI). Tubulointerstitial fibrosis of the kidney is also a pathological finding observed in CRD and involves composition of extracellular matrix (ECM). However, an association between these two events has not been elucidated. In this study, we showed that the extracellular-to-intracellular scaffold protein integrin-linked kinase (ILK) regulates expression of tubular water channel aquaporin-2 (AQP2) and its apical membrane presence in the renal tubule. Basally, polyuria and decreased urine osmolality were present in ILK conditional-knockdown (cKD-ILK) adult mice compared with nondepleted ILK littermates. No changes were observed in arginine-vasopressin (AVP) blood levels, renal receptor (V2R), or AQP3 expression. However, tubular AQP2 was decreased in expression and apical membrane presence in cKD-ILK mice, where the canonical V2R/cAMP axis activation is still functional, but independent of the absence of ILK. Thus, cKD-ILK constitutes a nephrogenic diabetes insipidus (NDI) model. AQP2 and ILK colocalize in cultured inner medullary collecting duct (mIMCD3) cells. Specific ILK siRNAs and collagen I (Col) decrease ILK and AQP2 levels and AQP2 presence on the membrane of tubular mIMCD3 cells, which impairs the capacity of the cells to transport water under hypotonic stress. The present work points to ILK as a therapeutic target in NDI.

Integrin-linked kinase regulates vasomotor function by preventing endothelial nitric oxide synthase uncoupling: role in atherosclerosis.

RATIONALE: Atherosclerotic lesions develop in regions of disturbed flow, whereas laminar flow protects from atherogenesis; however, the mechanisms involved are not completely elucidated. Integrins are mechanosensors of shear stress in endothelial cells, and integrin-linked kinase (ILK) is important for blood vessel integrity and cardiovascular development. OBJECTIVES: To explore the role of ILK in vascular function by studying conditionally ILK-deficient (cKO) mice and human atherosclerotic arteries. RESULTS: ILK expression was detected in the endothelial cell layer of nonatherosclerotic vessels but was absent from the endothelium of atherosclerotic arteries. Live ultrasound imaging revealed that acetylcholine-mediated vasodilatation was impaired in cKO mice. These mice exhibited lowered agonist-induced nitric oxide synthase (NOS) activity and decreased cyclic guanosine monophosphate and nitrite production. ILK deletion caused endothelial NOS (eNOS) uncoupling, reflected in reduced tetrahydrobiopterin (BH4) levels, increased BH2 levels, decreased dihydrofolate reductase expression, and increased eNOS-dependent generation of superoxide accompanied by extensive vascular protein nitration. ILK reexpression prevented eNOS uncoupling in cKO cells, whereas superoxide formation was unaffected by ILK depletion in eNOS-KO cells, indicating eNOS as a primary source of superoxide anion. eNOS and ILK coimmunoprecipitated in aortic lysates from control animals, and eNOS-ILK-shock protein 90 interaction was detected in human normal mammary arteries but was absent from human atherosclerotic carotid arteries. eNOS-ILK interaction in endothelial cells was prevented by geldanamycin, suggesting heat shock protein 90 as a binding partner. CONCLUSIONS: Our results identify ILK as a regulatory partner of eNOS in vivo that prevents eNOS uncoupling, and suggest ILK as a therapeutic target for prevention of endothelial dysfunction related to shear stress-induced vascular diseases.

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout ageing.

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mitochondrial genome in different tissues throughout ageing. We used ultrasensitive duplex sequencing to profile ~2.5 million mitochondrial genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloguing ~1.2 million mitochondrial somatic and ultralow-frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the light strand origin of replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared with primates with a surfeit of reactive oxygen species-associated G > T/C > A mutations, and that somatic mutations in protein-coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that 're-align' mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.

Ni-Ru supported on CeO2 obtained by mechanochemical milling for catalytic hydrogen production from ammonia.

Developing active and stable catalysts for carbon-free hydrogen production is crucial to mitigate the effects of climate change. Ammonia is a promising carbon-free hydrogen source, as it has a high hydrogen content and is liquid at low pressure, which allows its easy storage and transportation. We have recently developed a nickel-based catalyst with a small content of ruthenium supported on cerium oxide, which exhibits high activity and stability in ammonia decomposition. Here, we investigate mechanochemical milling for its synthesis, a faster and less energy-consuming technique than conventional ones. Results indicate that mechanochemical synthesis increases catalytic activity compared to the conventional incipient wetness impregnation method. The interaction between the metal precursors and the support is key in fine-tuning catalytic activity, which increases linearly with oxygen vacancies in the support. Moreover, the mechanochemical method modifies the oxidation state of Ni and Ru species, with a variation depending on the precursors.

Effect of virgin olive oil as spreadable preparation on atherosclerosis compared to dairy butter in Apoe-deficient mice.

Olive oil is the main source of lipid energy in the Mediterranean diet and there is strong evidence of its health benefits. The effect of extra virgin olive oil (EVOO) in the form of a preparation of spreadable virgin olive oil (S-VO) on the progression of atheroma plaques was investigated in Apoe-deficient mice, a model of accelerated atherosclerosis. METHODS: Two isocaloric Western purified diets containing 20% fat, either as S-VO or as dairy butter, were used to feed 28 males and 16 females of two-month-old Apoe-deficient mice for 12 weeks. S-VO was prepared by blending more than 75% virgin olive oil with other vegetal natural fat to obtain a solid fat. Plasma total cholesterol, triglycerides and HDL cholesterol were measured. Hepatic lipid droplets were analyzed. Areas of atherosclerotic aortic lesions were quantified in cross-sectional images of the proximal aorta and en face analysis of the whole aorta. RESULTS: Total plasma cholesterol was increased in mice on the butter-supplemented diet in both female and male mice compared to S-VO, and the ratio of TC/HDL-cholesterol was significantly lower in S-VO than in the butter diet, although only in males, and no differences in plasma triglycerides were observed. No significant differences in hepatic lipid droplets were observed between diets in either sex. Aortic lesion areas were significantly higher in mice consuming the butter versus the S-VO diet in both sexes. CONCLUSION: Extra virgin olive oil prepared in spreadable form maintained the delay in atheroma plaque progression compared to butter.

[Rh(III)(dmbpy)2Cl2]+ as a highly efficient catalyst for visible-light-driven hydrogen production in pure water: comparison with other rhodium catalysts.

We report a very efficient homogeneous system for the visible-light-driven hydrogen production in pure aqueous solution at room temperature. This comprises [Rh(III) (dmbpy)(2)Cl(2)]Cl (1) as catalyst, [Ru(bpy)(3)]Cl(2) (PS1) as photosensitizer, and ascorbate as sacrificial electron donor. Comparative studies in aqueous solutions also performed with other known rhodium catalysts, or with an iridium photosensitizer, show that 1) the PS1/1/ascorbate/ascorbic acid system is by far the most active rhodium-based homogeneous photocatalytic system for hydrogen production in a purely aqueous medium when compared to the previously reported rhodium catalysts, Na(3)[Rh(I) (dpm)(3)Cl] and [Rh(III)(bpy)Cp*(H(2)O)]SO(4) and 2) the system is less efficient when [Ir(III) (ppy)(2)(bpy)]Cl(PS2) is used as photosensitizer. Because catalyst 1 is the most efficient rhodium-based H(2)-evolving catalyst in water, the performance limits of this complex were further investigated by varying the PS1/1 ratio at pH 4.0. Under optimal conditions, the system gives up to 1010 turnovers versus the catalyst with an initial turnover frequency as high as 857 TON h(-1). Nanosecond transient absorption spectroscopy measurements show that the initial step of the photocatalytic H(2)-evolution mechanism is a reductive quenching of the PS1 excited state by ascorbate, leading to the reduced form of PS1, which is then able to reduce [Rh(III)(dmbpy)(2)Cl(2)](+) to [Rh(I)(dmbpy)(2)](+). This reduced species can react with protons to yield the hydride [Rh(III)(H)(dmbpy)(2)(H(2)O)](2+), which is the key intermediate for the H(2) production.

Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF).

Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILK resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing.

Trends in contraception use in Spanish adolescents and young adults (15 to 24 years) between 2002 and 2008.

OBJECTIVE: To assess changes in the use of contraceptive methods, and induced abortion rates, in Spanish adolescents and young adults aged 15 to 24 years, between 2002 and 2008. STUDY DESIGN: Representative samples of Spanish men and women aged 15 to 24 years were surveyed in 2002 (N = 1826) and 2008 (N = 2000). RESULTS: The rate of use of contraceptive methods increased from 61% in men and 60% in women in 2002 to 80% and 75%, respectively, in 2008. The most commonly used method was the condom (51% in 2002 and 71% in 2008), followed by the contraceptive pill (18% in 2002 and 18% in 2008). None of the adolescents and young adults surveyed used natural methods or the diaphragm, or had undergone sterilisation. The induced abortion rate increased from 9.28 to 13.48 per 1000 women in the group aged between 15 and 19 years, and from 14.37 to 21.05 per 1000 women in the group aged 20 to 24 years. CONCLUSION: Despite an increase in the use of effective birth control methods, the rates of abortion rose during the study period, which may indicate that compliance with the use of condoms is inadequate. There is an urgent need to develop educational campaigns or to design specific policies addressing contraception-related issues for young people.

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging.

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. We used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging ~1.2 million mitochondrial somatic and ultra low frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared to primates with a surfeit of reactive oxygen species-associated G>T/C>A mutations, and that somatic mutations in protein coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that "re-align" mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.

Enhancing in vivo retinol bioavailability by incorporating ß-carotene from alga Dunaliella salina into nanoemulsions containing natural-based emulsifiers.

The use of microalgae as a source of bioactive compounds has gained interest since they present advantages vs higher plants. Among them, Dunaliella salina is one of the best sources of natural ß-carotene, which is the precursor of vitamin A. However, ß-carotene shows reduced oral bioavailability due to its chemical degradation and poor absorption. The work aimed to evaluate the influence of the emulsifier and oil concentration on the digestive stability of Dunaliella Salina-based nanoemulsions and study their influence on the digestibility and the ß-carotene bioaccessibility. In addition, the effect of the emulsifier nature on the absorption of ß-carotene and its conversion to retinol in vivo was also investigated. Results showed that the coalescence observed in soybean lecithin nanoemulsion during the gastrointestinal digestion reduced the digestibility and ß-carotene bioaccessibility. In contrast, whey protein nanoemulsion that showed aggregation in the gastric phase could be redispersed in the intestinal phase facilitating the digestibility and bioaccessibility of the compound. In vivo results confirmed that whey protein nanoemulsion increased the bioavailability of retinol to a higher extent (Cmax 685 ng/mL) than soybean lecithin nanoemulsion (Cmax 394 ng/mL), because of an enhanced ß-carotene absorption.

Effect of the Emulsifier Used in Dunaliella salina-Based Nanoemulsions Formulation on the ß-Carotene Absorption and Metabolism in Rats.

SCOPE: Microalgae such as Dunaliella salina are a potential sustainable source of natural ß-carotene due to their fast growth and high adaptability to environmental conditions. This work aims to evaluate the effect of the incorporation of ß-carotene from this alga into different emulsifier-type nanoemulsions (soybean lecithin [SBL], whey protein isolate [WPI], sodium caseinate [SDC]) on its absorption, metabolization, and biodistribution in rats. METHODS AND RESULTS: Nanoemulsions formulated with different emulsifiers at 8% concentration are obtained by five cycles of microfluidization at 130 mPa, then expose to an in vitro digestion or orally administer to rats. Feeding rats with nanoemulsions improves ß-carotene uptake compared to control suspension, especially using SDC and WPI as emulsifiers. A greater presence of ß-carotene and retinol in the intestine, plasma, and liver is observed, being the liver the tissue that shows the highest accumulation. This fact can be a consequence of the smaller droplets that protein-nanoemulsions present compared to that with SBL in the intestine of rats, which promote faster digestibility and higher ß-carotene bioaccessibility (35%-50% more) according to the in vitro observations. CONCLUSIONS: Nanoemulsions, especially those formulated with protein emulsifiers, are effective systems for increasing ß-carotene absorption, as well as retinol concentration in different rat tissues.

Emulsion-Based Delivery Systems to Enhance the Functionality of Bioactive Compounds: Towards the Use of Ingredients from Natural, Sustainable Sources.

In recent years, the trend in the population towards consuming more natural and sustainable foods has increased significantly. This claim has led to the search for new sources of bioactive compounds and extraction methods that have less impact on the environment. Moreover, the formulation of systems to protect these compounds is also focusing on the use of ingredients of natural origin. This article reviews novel, natural alternative sources of bioactive compounds with a positive impact on sustainability. In addition, it also contains information on the most recent studies based on the use of natural (especially from plants) emulsifiers in the design of emulsion-based delivery systems to protect bioactive compounds. The properties of these natural-based emulsion-delivery systems, as well as their functionality, including in vitro and in vivo studies, are also discussed. This review provides relevant information on the latest advances in the development of emulsion delivery systems based on ingredients from sustainable natural sources.

Enhanced in vivo absorption and biodistribution of curcumin loaded into emulsions with high medium-chain triglyceride content.

The health benefits of curcumin have been demonstrated by several clinical studies, but its low bioavailability compromises its functionality. In this regard, emulsions have proven to be effective encapsulation systems for curcumin. Nevertheless, emulsions with a high oil content (50%) may offer some advantages due to the large amount of compound they can incorporate. Therefore, the aim of this work was to study the pharmacokinetics and biodistribution of curcumin when carried in optimized emulsions containing 50% MCT oil and a plant-based emulsifier (soybean lecithin) at 2 h or 4 h post-oral administration to rats. The most stable emulsion was obtained using 50% of oil and a surfactant-oil-ratio 0.1, through a microfluidization process. After the oral administration of the systems (150 mg curcumin/kg body weight), curcumin glucuronide was the main compound present in plasma (AUC0-t = 1556.3 ng·h·ml-1), especially at 2-4 h post-administration. The total curcuminoid bioavailability was increased by 10.6-fold when rats were fed with the curcumin emulsion rather than with a control suspension. Moreover, rats fed with the emulsion showed the highest accumulation of free curcuminoids, which present the highest biological activity, in the liver (129 ng curcumin/g tissue) and brown adipose tissue (193 ng curcumin/g tissue). The obtained results are of great interest since the presence of curcumin in the brown adipose tissue has been shown to play a relevant role in the prevention of obesity and its related metabolic disorders.