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Nutrients, Volume 12, Issue 1 (January 2020) – 273 articles

Cover Story (view full-size image): Pregnancy ongoing and the labor setting are related by physiological changes of the mother and the placenta microbiota through different mechanisms. Even, the classical belief of the sterile fetus is under discussion. In addition, the newborn progress and child development are also influenced by their microbiota. New molecular methods complemented with metabolomics and proteomic analysis will complete the whole metabolic picture of the microbiota and its influence in the perinatal period, taking into account different factors such as the diet, ethnicity and geographic location of the mothers. This knowledge may help predict possible complications that could occur during pregnancy, childbirth and subsequent child growth, that might be prevented. View this paper
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67 pages, 559 KiB  
Editorial
Acknowledgement to Reviewers of Nutrients in 2019
by Nutrients Editorial Office
Nutrients 2020, 12(1), 273; https://doi.org/10.3390/nu12010273 - 20 Jan 2020
Cited by 1 | Viewed by 10205
Abstract
The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article
12 pages, 267 KiB  
Article
Influence of Dietary Advice Including Green Vegetables, Beef, and Whole Dairy Products on Recurrent Upper Respiratory Tract Infections in Children: A Randomized Controlled Trial
by Ellen van der Gaag, Ruben Brandsema, Rosan Nobbenhuis, Job van der Palen and Thalia Hummel
Nutrients 2020, 12(1), 272; https://doi.org/10.3390/nu12010272 - 20 Jan 2020
Cited by 12 | Viewed by 11757
Abstract
Background: Since no treatment exists for children suffering from upper respiratory tract infections (URTIs) without immunological disorders, we searched for a possible tool to improve the health of these children. Aim: We evaluated whether dietary advice (based on food matrix and food synergy), [...] Read more.
Background: Since no treatment exists for children suffering from upper respiratory tract infections (URTIs) without immunological disorders, we searched for a possible tool to improve the health of these children. Aim: We evaluated whether dietary advice (based on food matrix and food synergy), including standard supportive care, can decrease the number and duration of URTIs in children with recurrent URTIs. Design and Setting: This study was a multicenter randomized controlled trial in two pediatric outpatient clinics in the Netherlands, with 118 children aged one to four years with recurrent URTIs. The dietary advice group received dietary advice plus standard supportive care, while the control group received standard supportive care alone for six months. The dietary advice consisted of green vegetables five times per week, beef three times per week, 300 mL whole milk per day, and whole dairy butter on bread every day. Portion sizes were age-appropriate. Results and Conclusion: Children in the dietary advice group had 4.8 (1.6–9.5) days per month with symptoms of an URTI in the last three months of the study, compared to 7.7 (4.0–12.3) in the control group (p = 0.028). The total number of URTIs during the six-month study period was 5.7 (±0.55) versus 6.8 (±0.49), respectively (p = 0.068). The use of antibiotics was significantly reduced in the dietary advice group, as well as visits to a general practitioner, thereby possibly reducing healthcare costs. The results show a reduced number of days with symptoms of a URTI following dietary advice. The number of infections was not significantly reduced. Full article
15 pages, 1950 KiB  
Article
Antihypertensive Effects of Virgin Olive Oil (Unfiltered) Low Molecular Weight Peptides with ACE Inhibitory Activity in Spontaneously Hypertensive Rats
by Juan María Alcaide-Hidalgo, Miguel Romero, Juan Duarte and Eduardo López-Huertas
Nutrients 2020, 12(1), 271; https://doi.org/10.3390/nu12010271 - 20 Jan 2020
Cited by 37 | Viewed by 5977
Abstract
The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We hypothesised that unfiltered VOO could possess low molecular weight peptides with antihypertensive activity. We produced unfiltered VOO and obtained a water-soluble peptide extract from it. The peptides were [...] Read more.
The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We hypothesised that unfiltered VOO could possess low molecular weight peptides with antihypertensive activity. We produced unfiltered VOO and obtained a water-soluble peptide extract from it. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. We selected 23 peptide sequences containing between 6 and 9 amino acids and molecular masses ranging 698–1017 Da. Those peptides were chemically synthesised and their angiotensin-converting enzyme (ACE) inhibitory activity was studied in vitro. Seven peptides showed a strong activity, with half maximal inhibitory concentration (IC50) <10 µm. The antihypertensive effects of the four most active synthesised ACE inhibitor peptides were studied in spontaneously hypertensive rats (SHR). Acute oral administration of synthetic peptides RDGGYCC and CCGNAVPQ showed antihypertensive activity in SHR. We conclude that unfiltered VOO naturally contains low molecular weight peptides with specific ACE inhibitory activity and antihypertensive effects in SHR. Full article
(This article belongs to the Section Micronutrients and Human Health)
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<p>Separation of peptides extracted from unfiltered virgin olive oil by gel filtration chromatography and FPLC.</p>
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<p>Angiotensin-converting enzyme (ACE) inhibitory activity (expressed as IC<sub>50</sub>) of water-soluble unfiltered virgin olive oil extract and of the fast protein liquid chromatography (FPLC)-purified fractions F1–F6. Data are expressed as mean values ± SD (bars).</p>
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<p>Analysis by nano- LC-Orbitrap MS/MS of water-soluble peptides extracted from unfiltered virgin olive oil. The total ion chromatogram and retention times of the selected ACE inhibitory peptides are shown. Brackets show the number of peptides with the same retention time.</p>
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<p>Fragmentation spectra of water-soluble peptides extracted from unfiltered virgin olive oil and of the corresponding purified synthetic peptides (below) analysed by nano- LC-Orbitrap MS/MS and PEAKS Studio software. (<b>A</b>), peptide No. 1, RDGGYCC; (<b>B</b>), peptide No. 2, LEEFCC; (<b>C</b>), peptide No. 3 HCGCNTH; and (<b>D</b>), peptide No. 4 CCGNAVPQ. Fragment ion tables for b and y ions (monoisotopic masses) are included.</p>
Full article ">Figure 4 Cont.
<p>Fragmentation spectra of water-soluble peptides extracted from unfiltered virgin olive oil and of the corresponding purified synthetic peptides (below) analysed by nano- LC-Orbitrap MS/MS and PEAKS Studio software. (<b>A</b>), peptide No. 1, RDGGYCC; (<b>B</b>), peptide No. 2, LEEFCC; (<b>C</b>), peptide No. 3 HCGCNTH; and (<b>D</b>), peptide No. 4 CCGNAVPQ. Fragment ion tables for b and y ions (monoisotopic masses) are included.</p>
Full article ">Figure 4 Cont.
<p>Fragmentation spectra of water-soluble peptides extracted from unfiltered virgin olive oil and of the corresponding purified synthetic peptides (below) analysed by nano- LC-Orbitrap MS/MS and PEAKS Studio software. (<b>A</b>), peptide No. 1, RDGGYCC; (<b>B</b>), peptide No. 2, LEEFCC; (<b>C</b>), peptide No. 3 HCGCNTH; and (<b>D</b>), peptide No. 4 CCGNAVPQ. Fragment ion tables for b and y ions (monoisotopic masses) are included.</p>
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<p>Systolic blood pressure (SBP) changes (mmHg) detected in spontaneously hypertensive rats (SHR) at baseline and 2, 4, 8 and 24 h after the administration of a 25 mg/kg BW dose of synthetic peptides No. 1 (RDGGYCC, ●), No. 2 (LEEFCC, ▲), No.3 (HCGCNTH, ▼), No.4 (CCGNAVPQ, ■), Captopril (50 mg/kg of BW, □), or water control (○). * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01 vs. control.</p>
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13 pages, 2162 KiB  
Article
Decreased PEDF Promotes Hepatic Fatty Acid Uptake and Lipid Droplet Formation in the Pathogenesis of NAFLD
by Kuang-Tzu Huang, Kuang-Den Chen, Li-Wen Hsu, Chao-Pin Kung, Shu-Rong Li, Chien-Chih Chen, King-Wah Chiu, Shigeru Goto and Chao-Long Chen
Nutrients 2020, 12(1), 270; https://doi.org/10.3390/nu12010270 - 20 Jan 2020
Cited by 8 | Viewed by 5208
Abstract
Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression. Full article
(This article belongs to the Section Nutrition and Metabolism)
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<p>Decreased pigment epithelium-derived factor (PEDF) and increased CD36 were observed in hepatic steatosis. (<b>A</b>) Magnification: 100×. C57BL/6 mice were on a control or choline-deficient <span class="html-small-caps">l</span>-amino acid-defined (CDAA) diet for 8 weeks. Liver sections were stained with hematoxylin and eosin (H&amp;E) for histological evaluation. (<b>B</b>) Hepatic gene expression was determined using quantitative RT-PCR. (<b>C</b>) Magnification: 100×. Hepatic PEDF and CD36 proteins were stained using immunohistochemical analysis. (<b>D</b>) Gene expression in the adipose tissue was determined using quantitative RT-PCR. *, Statistically significant compared with the controls at <span class="html-italic">p</span> &lt; 0.05. ATGL: adipose triglyceride lipase.</p>
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<p>Knocking down PEDF increases lipid droplet accumulation and fatty acid uptake. (<b>A</b>) Magnification: 100×. Hep3B cells were transfected with control or PEDF siRNA, followed by incubation with vehicle or fatty acid mixture (palmitic acid (PA)/oleic acid (OA)) for 24 h. Lipid droplet accumulation was assayed by BODIPY 493/503 staining. (<b>B</b>) Magnification: 100×. Control and PEDF siRNA-transfected Hep3B cells were incubated with BODIPY FL C16 to assay fatty acid uptake. Fluorescence was then normalized to DAPI stained cell number. (<b>C</b>) Control and PEDF siRNA-transfected Hep3B cells were treated with PA/OA. Gene expression was determined using quantitative RT-PCR for CD36 and PPARγ and (<b>D</b>) immunoblotting for CD36. CD36 band intensity was quantified, normalized to that of GAPDH, and presented as mean ± standard deviation. GW9662: PPARγ inhibitor (5 μM). *, Statistically significant compared with the untreated (or control transfected, untreated) group at <span class="html-italic">p</span> &lt; 0.05; #, statistically significant compared with the PEDF siRNA, untreated group at <span class="html-italic">p</span> &lt; 0.05. siRNA: small interfering RNA. PPARγ: peroxisome proliferator-activated receptor γ.</p>
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<p>Knocking down PEDF increases hepatic fatty acid mobilization. (<b>A</b>) Magnification: 100×. Hep3B cells were transfected with control or PEDF siRNA before incubation with BODIPY 558/568 C12 (1 μM) for 6 h, followed by OA (0.1 mM) or OA + Atglistatin (25 μM) treatment for 16 h. Lipid droplets were stained with BODIPY 493/503 and nuclei were stained with DAPI. Scale bar: 200 μm. (<b>B</b>) Lipid droplet accumulation was calculated by quantification of the BODIPY 493/503 fluorescent intensity normalized to the cell number. (<b>C</b>) Mobilization of fatty acids was calculated by quantification of red signal intensity of the merged images, divided by the cell number. *, Statistically significant compared with the control transfected group at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Decreased PEDF results in gene expression changes toward hepatic lipid accumulation. (<b>A</b>) Control and PEDF siRNA transfected Hep3B cells were treated with OA (0.1 mM) or OA + Atglistatin (25 μM) for 24 h. Adipose triglyceride lipase (ATGL) protein levels were determined using immunoblotting. ATGL band intensity was quantified and normalized to that of β-actin. (<b>B</b>) Gene expression was determined using quantitative RT-PCR. (<b>C</b>) Hierarchical clustering dendrogram showing non-alcoholic fatty liver disease (NAFLD)-related differentially expressed genes (DEGs) by comparing control with PEDF siRNA transfected Hep3B samples. *, Statistically significant compared with the controls at at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Hepatic PEDF is downregulated by fatty acids OA and PA. Hep3B cells were treated with various concentrations of fatty acids (OA, PA, or combined) for 24 h. PEDF expression was evaluated using quantitative RT-PCR. *, Statistically significant compared with the control group at <span class="html-italic">p</span> &lt; 0.05.</p>
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9 pages, 520 KiB  
Communication
Carotenoids and Periodontal Infection
by Koji Naruishi
Nutrients 2020, 12(1), 269; https://doi.org/10.3390/nu12010269 - 20 Jan 2020
Cited by 7 | Viewed by 5530
Abstract
Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as [...] Read more.
Periodontitis is a polymicrobial infectious disease that leads to inflammation of the gingiva, resulting in teeth loss by various causes such as inflammation-mediated bone resorption. Recently, many investigators have reported that the periodontitis resulting from persistent low-grade infection of Gram-negative bacteria such as Porphyromonas gingivalis (Pg) is associated with increased atherosclerosis, diabetes mellitus, and other systemic diseases through blood stream. On the other hand, carotenoids belong among phytochemicals that are responsible for different colors of the foods. It is important to examine whether carotenoids are effective to the inhibition of periodontal infection/inflammation cascades. This review summarizes the advanced state of knowledge about suppression of periodontal infection by several carotenoids. A series of findings suggest that carotenoids intake may provide novel strategy for periodontitis treatment, although further study will be needed. Full article
(This article belongs to the Special Issue Carotenoids in Human Nutrition)
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<p>Crosstalk of HGFs and inflammatory cells: Potential biological mechanisms of periodontitis. In inflamed periodontal tissues, IL-1 induces sIL-6R production in infiltrated inflammatory cells such as M. Furthermore, IL-1 induces production of IL-6 in HGFs. Finally, IL-6/sIL-6R complexes induce MMP-1, cathepsins, bFGF and VEGF production in HGFs, resulting in progression of periodontitis.</p>
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16 pages, 466 KiB  
Review
Do Dietary Supplements and Nutraceuticals Have Effects on Dental Implant Osseointegration? A Scoping Review
by Livia Nastri, Antimo Moretti, Silvia Migliaccio, Marco Paoletta, Marco Annunziata, Sara Liguori, Giuseppe Toro, Massimiliano Bianco, Gennaro Cecoro, Luigi Guida and Giovanni Iolascon
Nutrients 2020, 12(1), 268; https://doi.org/10.3390/nu12010268 - 20 Jan 2020
Cited by 24 | Viewed by 8080
Abstract
Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients’ nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the [...] Read more.
Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients’ nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP identified micronutrients from the “European Union (EU) Register of nutrition and health claims made on foods” that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH (Medical Subject Headings) terms and adding to each of them the words “dental implants” and “osseointegration”. The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the “EU Register on nutrition and health claims” for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation. Full article
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<p>Flow diagram of sources selection process.</p>
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16 pages, 1238 KiB  
Article
Maternal Selenium Deficiency in Mice Alters Offspring Glucose Metabolism and Thyroid Status in a Sexually Dimorphic Manner
by Pierre Hofstee, Daniel R. McKeating, Lucy A. Bartho, Stephen T. Anderson, Anthony V. Perkins and James S. M. Cuffe
Nutrients 2020, 12(1), 267; https://doi.org/10.3390/nu12010267 - 20 Jan 2020
Cited by 26 | Viewed by 5760
Abstract
Selenium is an essential micronutrient commonly deficient in human populations. Selenium deficiency increases the risks of pregnancy complications; however, the long-term impact of selenium deficiency on offspring disease remains unclear. This study investigates the effects of selenium deficiency during pregnancy on offspring metabolic [...] Read more.
Selenium is an essential micronutrient commonly deficient in human populations. Selenium deficiency increases the risks of pregnancy complications; however, the long-term impact of selenium deficiency on offspring disease remains unclear. This study investigates the effects of selenium deficiency during pregnancy on offspring metabolic function. Female C57BL/6 mice were allocated to control (>190 μg selenium/kg, n = 8) or low selenium (<50 μg selenium/kg, n = 8) diets prior to mating and throughout gestation. At postnatal day (PN) 170, mice underwent an intraperitoneal glucose tolerance test and were culled at PN180 for biochemical analysis. Mice exposed to selenium deficiency in utero had reduced fasting blood glucose but increased postprandial blood glucose concentrations. Male offspring from selenium-deficient litters had increased plasma insulin levels in conjunction with reduced plasma thyroxine (tetraiodothyronine or T4) concentrations. Conversely, females exposed to selenium deficiency in utero exhibited increased plasma thyroxine levels with no change in plasma insulin. This study demonstrates the importance of adequate selenium intake around pregnancy for offspring metabolic health. Given the increasing prevalence of metabolic disease, this study highlights the need for appropriate micronutrient intake during pregnancy to ensure a healthy start to life. Full article
(This article belongs to the Special Issue Diet, Nutrition and Fetal Programming)
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<p>Offspring weights, food and water consumption. Body weight at (<b>A</b>) PN30 and (<b>B</b>) PN180 as well as average daily consumption of (<b>C</b>) normal chow and (<b>D</b>) water from weaning until PN180. Open bars (white) indicate offspring from litters that consumed a normal selenium diet, whereas closed bars (black) are offspring from litters that consumed a low selenium diet throughout pregnancy and up until weaning. Data are mean ± SEM and analysed by two-way ANOVA with treatment (<span class="html-italic">P</span><sub>trt</sub>) and sex (<span class="html-italic">P</span><sub>sex</sub>) as major factors. <span class="html-italic">P</span><sub>int</sub> represents the interaction between trt and sex. Multiple comparisons were determined by Sidak posthoc testing. Significance determined by <span class="html-italic">p</span> &lt; 0.05. <span class="html-italic">n</span> = 6–9.</p>
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<p>Offspring glucose metabolism. Offspring random glucose concentrations at (<b>A</b>) PN30 and fasting blood glucose concentrations at (<b>B</b>) PN90 and (<b>C</b>) PN170. Following an intraperitoneal (IP) of glucose at PN170, the following parameters were determined: (<b>D</b>) GTT area under the glucose curve (AUGC), (<b>E</b>) peak blood glucose concentrations 30 min post IP and (<b>F</b>) blood glucose concentrations 180 min post IP. Open bars (white) indicate offspring from litters that consumed a normal selenium diet, whereas closed bars (black) are offspring from litters that consumed a low selenium diet throughout pregnancy and up until weaning. Data are mean ± SEM and analysed by two-way ANOVA with treatment (<span class="html-italic">P</span><sub>trt</sub>) and sex (<span class="html-italic">P</span><sub>sex</sub>) as major factors. <span class="html-italic">P</span><sub>int</sub> represents the interaction between treatment and sex. Multiple comparisons were determined by Sidak posthoc testing. * = <span class="html-italic">p</span> &lt; 0.05, ** = <span class="html-italic">p</span> &lt; 0.01 compared to control of same sex. <span class="html-italic">n</span> = 6–9.</p>
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<p>Offspring plasma hormone levels. PN180 plasma levels of (<b>A</b>) insulin, (<b>B</b>) corticosterone, (<b>C</b>) tetraiodothyronine (thyroxine) and (<b>D</b>) triiodothyronine. Open bars (white) indicate offspring from litters that consumed a normal selenium diet, whereas closed bars (black) are offspring from litters that consumed a low selenium diet throughout pregnancy and up until weaning. Data are mean ± SEM and analysed by two-way ANOVA with treatment (<span class="html-italic">P</span><sub>trt</sub>) and sex (<span class="html-italic">P</span><sub>sex</sub>) as major factors. <span class="html-italic">P</span><sub>int</sub> represents the interaction between treatment and sex. Multiple comparisons were determined by Sidak posthoc testing. * = <span class="html-italic">p</span> &lt; 0.05, ** = <span class="html-italic">p</span> &lt; 0.01 compared to control of same sex. <span class="html-italic">n</span> = 6–9.</p>
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<p>Insulin receptor pathway in the skeletal muscle of offspring. PN180 insulin receptor pathway mRNA and protein expression in the gastrocnemius. Expression of (<b>A</b>) <span class="html-italic">Slc2a4</span>, (<b>B</b>) <span class="html-italic">Insr</span>, (<b>C</b>) <span class="html-italic">Pik3c3</span>, (<b>D</b>) <span class="html-italic">Akt2</span>, (<b>E</b>) <span class="html-italic">Gsk3b</span> and (<b>F</b>) <span class="html-italic">Pgk1</span> in males and females at PN180. Protein expression of (<b>G</b>) GLUT4 and (<b>H</b>) Pan-AKT is shown in both males and females. Open bars (white) indicate offspring from litters that consumed a normal selenium diet, whereas closed bars (black) are offspring from litters that consumed a low selenium diet throughout pregnancy and up until weaning. Data are mean ± SEM and analysed by unpaired <span class="html-italic">t</span>-tests between mice for litters on a normal selenium diet and a low selenium diet in both males and females. * = <span class="html-italic">p</span> &lt; 0.05, ** = <span class="html-italic">p</span> &lt; 0.01, *** = <span class="html-italic">p</span> &lt; 0.001 compared to control of same sex. <span class="html-italic">n</span> = 6–8.</p>
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<p>Thyroid hormone transporters and receptors in offspring skeletal muscle. PN180 mRNA expression in the gastrocnemius of thyroid hormone transporters and receptors. Expression of (<b>A</b>) <span class="html-italic">ThrA,</span> (<b>B</b>) <span class="html-italic">ThrB</span>, (<b>C</b>) <span class="html-italic">Mct10</span> and (<b>D</b>) <span class="html-italic">Ucp3</span> in males and females at PN180. Open bars (white) indicate offspring from litters that consumed a normal selenium diet, whereas closed bars (black) are offspring from litters that consumed a low selenium diet throughout pregnancy and up until weaning. Data are mean ± SEM and were analysed by unpaired t-tests between mice for litters on a normal selenium diet and a low selenium diet in both males and females. * = <span class="html-italic">p</span> &lt; 0.05 compared to control of same sex. <span class="html-italic">n</span> = 6–8.</p>
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14 pages, 456 KiB  
Article
Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology
by Michał Wiciński, Ewelina Sawicka, Jakub Gębalski, Karol Kubiak and Bartosz Malinowski
Nutrients 2020, 12(1), 266; https://doi.org/10.3390/nu12010266 - 20 Jan 2020
Cited by 181 | Viewed by 19574
Abstract
The first months of life are a special time for the health development and protection of infants. Breastfeeding is the natural and best way of feeding an infant, and positively influences their development and health. Breast milk provides the ideal balance of nutrients [...] Read more.
The first months of life are a special time for the health development and protection of infants. Breastfeeding is the natural and best way of feeding an infant, and positively influences their development and health. Breast milk provides the ideal balance of nutrients for the infant and contains countless bioactive ingredients such as immunoglobulins, hormones, oligosaccharides and others. Human milk oligosaccharides (HMOs) are a very important and interesting constituent of human milk, and are the third most abundant solid component after lactose and lipids. They are a structurally and biologically diverse group of complex indigestible sugars. This article will discuss the mechanisms of action of HMOs in infants, such as their anti-adhesive properties, properties modulating the immune system, and impact on bacterial flora development. Many health benefits result from consuming HMOs. They also may decrease the risk of infection by their interactions with viruses, bacteria or protozoa. The commercial use of HMOs in infant formula, future directions, and research on the use of HMOs as a therapy will be discussed. Full article
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<p>Representative structure of HMO and the major oligosaccharides found in breast milk. (<b>a</b>) Possible linkages of HMO building blocks, (<b>b</b>) type 1 (LNT) and type 2 chains (LNnT) (<b>c</b>) structures of 2′FL, 3′FL and 6′FL.</p>
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20 pages, 3954 KiB  
Article
Seabuckthorn (Hippophaë rhamnoides) Freeze-Dried Powder Protects against High-Fat Diet-Induced Obesity, Lipid Metabolism Disorders by Modulating the Gut Microbiota of Mice
by Caixia Guo, Li Han, Meiping Li and Ligang Yu
Nutrients 2020, 12(1), 265; https://doi.org/10.3390/nu12010265 - 20 Jan 2020
Cited by 36 | Viewed by 5593
Abstract
This study aimed to investigate the beneficial effects of seabuckthorn freeze-dried powder on high-fat diet-induced obesity and related lipid metabolism disorders, and further explored if this improvement is associated with gut microbiota. Results showed that seabuckthorn freeze-dried powder administration decreased body weight, Lee’s [...] Read more.
This study aimed to investigate the beneficial effects of seabuckthorn freeze-dried powder on high-fat diet-induced obesity and related lipid metabolism disorders, and further explored if this improvement is associated with gut microbiota. Results showed that seabuckthorn freeze-dried powder administration decreased body weight, Lee’s index, adipose tissue weight, liver weight, and serum lipid levels. Moreover, treatment with seabuckthorn freeze-dried powder effectively reduced fat accumulation by modulating the relative expression of genes involved in lipid metabolism through down-regulation of encoding lipogenic and store genes, including SREBP-1c, PPAR-γ, ACC, and SCD1, and up-regulation of regulating genes of fatty acid oxidation, including HSL, CPT-1, and ACOX. Especially, seabuckthorn freeze-dried powder regulated the composition of gut microbiota, such as increasing the ratio of Firmicutes/Bacteroidetes, decreasing relative abundance of harmful bacteria (Desulfovibrio), and increasing relative abundance of beneficial bacteria (Akkermansia and Bacteroides). The changes of beneficial bacteria had a positive correlation with genes encoding lipolysis and a negative correlation with genes encoding lipid lipogenesis and store. The harmful bacteria were just the opposite. Besides, changes in gut microbiota had an obvious effect in the secretion of main metabolites—short-chain fatty acids (SCFAs), especially propionic acid. Thus, our results indicated that the seabuckthorn freeze-dried powder could ameliorate high-fat diet-induced obesity and obesity-associated lipid metabolism disorders by changing the composition and structure of gut microbiota. Full article
(This article belongs to the Special Issue Diet, Gut Microbiota and Metabolic Disorders)
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<p>Effects of seabuckthorn freeze-dried powder on the feature indexes of obesity in C57BL/6 obesity mice reduced by the high-fat diet. NC: the mice of normal diet, HFD: the mice of high-fat diet, HSFP: the mice of high-fat diet united by gavaging the homogenate of seabuckthorn freeze-dried powder. (<b>A</b>) Body size of representative mice. (<b>B</b>) Growth curve of mice. (<b>C</b>) Body weight gain and Lee’s index (Lee’s index = <math display="inline"><semantics> <mrow> <mroot> <mrow> <mfrac bevelled="true"> <mrow> <mi>b</mi> <mi>o</mi> <mi>d</mi> <mi>y</mi> <mo> </mo> <mi>w</mi> <mi>e</mi> <mi>i</mi> <mi>g</mi> <mi>h</mi> <mi>t</mi> <mo>∗</mo> <mn>1000</mn> </mrow> <mrow> <mi>b</mi> <mi>o</mi> <mi>d</mi> <mi>y</mi> <mo> </mo> <mi>l</mi> <mi>e</mi> <mi>n</mi> <mi>g</mi> <mi>t</mi> <mi>h</mi> </mrow> </mfrac> </mrow> <mn>3</mn> </mroot> </mrow> </semantics></math>. (<b>D</b>) Food intake and energy intake. (<b>E</b>) Food efficiency ratio: (weight gain/food intake for the whole experiment period) × 100) and energy efficiency ratio: (weight gain/energy intake for the entire experiment period) × 100). In our study, all data were expressed as means ± SD, graph bars with different letters on the top correspond to statistically significant results (<span class="html-italic">p</span> &lt; 0.05) based on one-way ANOVA analysis followed by Duncan’s multiple range test.</p>
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<p>Seabuckthorn freeze-dried powder supplementation attenuates high-fat diet-induced fat accumulation, adipocyte hypertrophy, and hepatic steatosis. (<b>A</b>) Anatomy, (<b>B</b>,<b>C</b>) total adipose tissue weight, and three parts adipose tissue weight. (<b>D</b>) Liver weight. (<b>E</b>) H&amp;E staining of epididymal white adipose tissue sections (scale: 100 μm, photographed at 400× magnification) and (<b>F</b>) average area of adipocyte. (<b>G</b>) H&amp;E staining of liver sections (scale: 200 μm, photographed at 200× magnification). In our study, all data are expressed as means ± SD. Graph bars with different letters on the top correspond to statistically significant results (<span class="html-italic">p</span> &lt; 0.05) based on one-way ANOVA analysis followed by Duncan’s multiple range test.</p>
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<p>Seabuckthorn freeze-dried powder regulated lipid metabolism. (<b>A</b>–<b>D</b>) were serum lipid indexes, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and the expression levels of genes related to lipid synthesis and oxidation of the epididymal white adipose tissue (<b>E</b>) and liver (<b>F</b>), including peroxisome proliferator-activated receptor-γ (PPAR-γ), acety1-CoA carboxylase (ACC), fatty acid syntheses (FAS), sterol regulatory element-bingding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-α (PPAR-α), stearoyl-CoA desaturase 1 (SCD1), CCAAT/enhancer-binding protein alpha (C/EBP-α), hormone-sensitive triglyceride lipase (HSL), carnitine palmitoyl transferase-1 (CPT-1), peroxisomal acyl coenzyme a oxidase (ACOX). All data are shown as means ± SD. Graph bars with different letters on the top correspond to statistically significant results (<span class="html-italic">p</span> &lt; 0.05) based on one-way ANOVA analysis followed by Duncan’s multiple range test.</p>
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<p>Seabuckthorn freeze-dried powder administration alters the composition and structure of gut microbiota. The composition and proportion of bacterial communities at the phylum (<b>A</b>,<b>B</b>), family (<b>C</b>) , and genus (<b>D</b>) level. Specific genus of bacteria (<b>E</b>); <span class="html-italic">Akkermansia</span> (<b>F</b>); <span class="html-italic">Desulfovibrio</span> (<b>G</b>). The relative abundance of short-chain fatty acids (SCFAs) in three groups. Data were shown as means ± SD. Graph bars with different letters on the top correspond to statistically significant results (<span class="html-italic">p</span> &lt; 0.05) based on one-way ANOVA analysis followed by Duncan’s multiple range test.</p>
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<p>Spearman’s correlation between the metabolic genes and the relative abundance top 20 bacteria at the genus level (<b>A</b>) metabolic genes in the adipose tissue; (<b>B</b>) metabolic genes in liver tissue. The different colors of bar represented the degree of association (red, positive correlation; blue, negative correlation).</p>
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14 pages, 408 KiB  
Article
Impact of Enhanced Recovery after Surgery with Preoperative Whey Protein-Infused Carbohydrate Loading and Postoperative Early Oral Feeding among Surgical Gynecologic Cancer Patients: An Open-Labelled Randomized Controlled Trial
by Ho Chiou Yi, Zuriati Ibrahim, Zalina Abu Zaid, Zulfitri ‘Azuan Mat Daud, Nor Baizura Md. Yusop, Jamil Omar, Mohd Norazam Mohd Abas, Zuwariah Abdul Rahman and Norshariza Jamhuri
Nutrients 2020, 12(1), 264; https://doi.org/10.3390/nu12010264 - 20 Jan 2020
Cited by 32 | Viewed by 7414
Abstract
Enhanced Recovery after Surgery (ERAS) with sole carbohydrate (CHO) loading and postoperative early oral feeding (POEOF) shortened the length of postoperative (PO) hospital stays (LPOHS) without increasing complications. This study aimed to examine the impact of ERAS with preoperative whey protein-infused CHO [...] Read more.
Enhanced Recovery after Surgery (ERAS) with sole carbohydrate (CHO) loading and postoperative early oral feeding (POEOF) shortened the length of postoperative (PO) hospital stays (LPOHS) without increasing complications. This study aimed to examine the impact of ERAS with preoperative whey protein-infused CHO loading and POEOF among surgical gynecologic cancer (GC) patients. There were 62 subjects in the intervention group (CHO-P), which received preoperative whey protein-infused CHO loading and POEOF; and 56 subjects formed the control group (CO), which was given usual care. The mean age was 49.5 ± 12.2 years (CHO-P) and 51.2 ± 11.9 years (CO). The trial found significant positive results which included shorter LPOHS (78.13 ± 33.05 vs. 99.49 ± 22.54 h); a lower readmission rate within one month PO (6% vs. 16%); lower weight loss (−0.3 ± 2.3 kg vs. −2.1 ± 2.3 kg); a lower C-reactive protein–albumin ratio (0.3 ± 1.2 vs. 1.1 ± 2.6); preserved muscle mass (0.4 ± 1.7 kg vs. −0.7 ± 2.6 kg); and better handgrip strength (0.6 ± 4.3 kg vs. −1.9 ± 4.7 kg) among CHO-P as compared with CO. However, there was no significant difference in mid-upper arm circumference and serum albumin level upon discharge. ERAS with preoperative whey protein-infused CHO loading and POEOF assured better PO outcomes. Full article
(This article belongs to the Special Issue Surgery and Nutrition)
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<p>Flow diagram for subject screening and recruitment.</p>
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11 pages, 1181 KiB  
Article
Circulating Ionized Magnesium: Comparisons with Circulating Total Magnesium and the Response to Magnesium Supplementation in a Randomized Controlled Trial
by Mary R. Rooney, Kyle D. Rudser, Alvaro Alonso, Lisa Harnack, Amy K. Saenger and Pamela L. Lutsey
Nutrients 2020, 12(1), 263; https://doi.org/10.3390/nu12010263 - 20 Jan 2020
Cited by 19 | Viewed by 4295
Abstract
Ionized Mg (iMg) is considered the biologically active fraction of circulating total Mg (tMg). It is possible that iMg may be a more physiologically relevant marker than tMg. Using data from a double-blind pilot randomized controlled trial, we tested (1) whether oral Mg [...] Read more.
Ionized Mg (iMg) is considered the biologically active fraction of circulating total Mg (tMg). It is possible that iMg may be a more physiologically relevant marker than tMg. Using data from a double-blind pilot randomized controlled trial, we tested (1) whether oral Mg supplementation will increase iMg concentrations compared with placebo and (2) the relationship between iMg and tMg at baseline. Additionally, we evaluated the agreement between iMg measured in fresh whole blood versus stored samples. A total of fifty-nine participants were randomized 1:1 to oral Mg supplementation (400 mg/day, Mg Oxide) or placebo for 10 weeks. Fasting blood samples were obtained at baseline and follow-up. The analysis used linear regression and an intent-to-treat approach. Participants were generally healthy, the mean age was 62, and 73% were female. The baseline iMg and tMg were modestly and positively associated (r = 0.50). The ratio of baseline iMg to tMg was 64%. The mean supplement effect on iMg was 0.03 mmol/L (95% CI:0.01, 0.05) for Mg supplementation versus placebo. The supplement effect on iMg was not statistically significantly different according to baseline iMg status (above/below median). Compared to fresh blood, iMg was consistently higher in refrigerated and frozen samples by 0.14 and 0.20 mmol/L, respectively. In this relatively healthy adult population, Mg supplementation over 10 weeks resulted in increased iMg concentrations. Whether iMg is a more appropriate measure of Mg status than tMg, and the public health or clinical utility of measuring iMg remains to be determined. Full article
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<p>Scatterplot and linear fitted line between ionized and total magnesium at baseline, unadjusted, n = 49. Normalized ionized Mg (iMg) concentration, which is adjusted for blood pH.</p>
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<p>Bland-Altman plot assessing the (<b>a</b>) change in ionized magnesium in response to magnesium supplementation over 10 weeks in the treatment arm, <span class="html-italic">n</span> = 22; (<b>b</b>) change in total magnesium in response to magnesium supplementation over 10 weeks in the treatment arm, <span class="html-italic">n</span> = 24; (<b>c</b>) change in ionized magnesium in response to magnesium supplementation over 10 weeks in the placebo arm, <span class="html-italic">n</span> = 27; (<b>d</b>) change in total magnesium in response to magnesium supplementation over 10 weeks in the placebo arm, <span class="html-italic">n</span> = 30. Normalized iMg concentration, which is adjusted for blood pH. Solid lines (black) are the mean difference ± 3 standard deviations; the long dash line (gray) is the fitted values; the short dash line (black) is the reference line for the mean difference of 0 mmol/L.</p>
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<p>Bland-Altman plot assessing the (<b>a</b>) change in ionized magnesium in response to magnesium supplementation over 10 weeks in the treatment arm, <span class="html-italic">n</span> = 22; (<b>b</b>) change in total magnesium in response to magnesium supplementation over 10 weeks in the treatment arm, <span class="html-italic">n</span> = 24; (<b>c</b>) change in ionized magnesium in response to magnesium supplementation over 10 weeks in the placebo arm, <span class="html-italic">n</span> = 27; (<b>d</b>) change in total magnesium in response to magnesium supplementation over 10 weeks in the placebo arm, <span class="html-italic">n</span> = 30. Normalized iMg concentration, which is adjusted for blood pH. Solid lines (black) are the mean difference ± 3 standard deviations; the long dash line (gray) is the fitted values; the short dash line (black) is the reference line for the mean difference of 0 mmol/L.</p>
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<p>Bland-Altman plot assessing the (<b>a</b>) association between ionized magnesium concentrations at baseline in fresh whole blood and in serum after refrigeration, <span class="html-italic">n</span> = 39; (<b>b</b>) the association between ionized magnesium concentrations at baseline in fresh whole blood and in serum following one freeze–thaw cycle, <span class="html-italic">n</span> = 39. Normalized iMg concentration, which is adjusted for blood pH. The median time in the fridge = 71 min. The median time frozen = 81 days. Solid lines (black) are the mean difference ± 3 standard deviations; the long dash line (gray) is the fitted values; the short dash line (black) is the reference line for the mean difference of 0 mmol/L.</p>
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<p>Bland-Altman plot assessing the (<b>a</b>) association between ionized magnesium concentrations at baseline in fresh whole blood and in serum after refrigeration, <span class="html-italic">n</span> = 39; (<b>b</b>) the association between ionized magnesium concentrations at baseline in fresh whole blood and in serum following one freeze–thaw cycle, <span class="html-italic">n</span> = 39. Normalized iMg concentration, which is adjusted for blood pH. The median time in the fridge = 71 min. The median time frozen = 81 days. Solid lines (black) are the mean difference ± 3 standard deviations; the long dash line (gray) is the fitted values; the short dash line (black) is the reference line for the mean difference of 0 mmol/L.</p>
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20 pages, 1756 KiB  
Article
p-Methoxycinnamic Acid Diesters Lower Dyslipidemia, Liver Oxidative Stress and Toxicity in High-Fat Diet Fed Mice and Human Peripheral Blood Lymphocytes
by Raquel Teixeira Terceiro Paim, Paula Salmito Alves Rodrigues, José Ytalo Gomes da Silva, Valdir Ferreira de Paula Junior, Bruno Bezerra da Silva, Claísa Andréa Silva De Freitas, Reinaldo Barreto Oriá, Eridan Orlando Pereira Tramontina Florean, Davide Rondina and Maria Izabel Florindo Guedes
Nutrients 2020, 12(1), 262; https://doi.org/10.3390/nu12010262 - 20 Jan 2020
Cited by 7 | Viewed by 4229
Abstract
The pursuit of cholesterol lowering natural products with less side effects is needed for controlling dyslipidemia and reducing the increasing toll of cardiovascular diseases that are associated with morbidity and mortality worldwide. The present study aimed at the examining effects of p-methoxycinnamic [...] Read more.
The pursuit of cholesterol lowering natural products with less side effects is needed for controlling dyslipidemia and reducing the increasing toll of cardiovascular diseases that are associated with morbidity and mortality worldwide. The present study aimed at the examining effects of p-methoxycinnamic acid diesters (PCO-C) from carnauba (Copernicia prunifera)-derived wax on cytotoxic, genotoxic responses in vitro and on dyslipidemia and liver oxidative stress in vivo, utilizing high-fat diet (HFD) chronically fed Swiss mice. In addition, we evaluated the effect of PCO-C on the expression of key cholesterol metabolism-related genes, as well as the structural interactions between PCO-C and lecithin-cholesterol acyl transferase (LCAT) in silico. Oral treatment with PCO-C was able to reduce total serum cholesterol and low-density lipoprotein (LDL) levels following HFD. In addition, PCO-C reduced excessive weight gain and lipid peroxidation, and increased the gene expression of LCAT following HFD. Furthermore, the high affinity of the studied compound (ΔG: −8.78 Kcal/mol) towards the active sites of mutant LCAT owing to hydrophobic and van der Waals interactions was confirmed using bioinformatics. PCO-C showed no evidence of renal and hepatic toxicity, unlike simvastatin, that elevated aspartate aminotransferase (AST) levels, a marker of liver dysfunction. Finally, PCO-C showed no cytotoxicity or genotoxicity towards human peripheral blood lymphocytes in vitro. Our results suggest that PCO-C exerts hypocholesterolemic effects. The safety of PCO-C in the toxicological tests performed and the reports of its beneficial biological effects render this a promising compound for the development of new cholesterol-lowering therapeutics to control dyslipidemia. More work is needed for further elucidating PCO-C role on lipid metabolism to support future clinical studies. Full article
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<p>Outline diagram of the in vivo experimental study.</p>
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<p>Structural representation of 4-methoxycinnamic acid diester (PCO-C).</p>
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<p>DNA damage index of human peripheral blood lymphocytes treated with PCO-C (10–250 µg/mL) assessed using the alkaline comet assay after 24 h of exposure. For dilution of the test substance, 0.4% Tween-80 was used. Doxorubicin (0.3 µg/mL) and 0.4% Tween-80 were used as the negative and positive controls, respectively. Bars represent the mean ± standard deviation of three independent experiments. * <span class="html-italic">p</span> &lt; 0.05; vs. control (0.4%Tween-80) according to ANOVA, followed by <span class="html-italic">Tukey</span> test.</p>
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<p>Effect of PCO-C on the transcription levels of liver LCAT (lecithin-cholesterol acyl transferase) mRNA. STD = standard chow diet; HFD = high fat diet; SIMV = simvastatin (20 mg/Kg/day); PCO-C = p-methoxycinnamic acid diesters (100 mg/Kg/day). Values are expressed as mean ± SEM of 7 mice per group. * <span class="html-italic">p</span> &lt; 0.05 versus HFD group. Relative gene expression levels were then calculated as 2<sup>−delta delta CT</sup>.</p>
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<p>Three-dimensional (3D) (<b>a</b>) and two-dimensional (2D) (<b>b</b>) arrangement of residues involved in the interaction of PCO-C with nLCAT (presence of Cys31), interaction with mLCAT (<b>c</b>) (presence of Tyr31). The residues were observed by the Accelrys visualizer software, version 4.5.</p>
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<p>3D (<b>a</b>) e 2D (<b>b</b>) arrangement of residues involved in the interaction of DTNB with nLCAT (B) (presence of Cys31), interaction with mLCAT (<b>c</b>) (presence of Tyr31). Residues were observed by the Accelrys visualizer software, version 4.5.</p>
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11 pages, 1502 KiB  
Communication
Regulation of Skeletal Muscle Function by Amino Acids
by Yasutomi Kamei, Yukino Hatazawa, Ran Uchitomi, Ryoji Yoshimura and Shinji Miura
Nutrients 2020, 12(1), 261; https://doi.org/10.3390/nu12010261 - 19 Jan 2020
Cited by 132 | Viewed by 25973
Abstract
Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of [...] Read more.
Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of the total body weight, plays important roles in exercise, energy expenditure, and glucose/amino acid usage—processes that are modulated by various amino acids and their metabolites. In this review, we address the metabolism and function of amino acids in the skeletal muscle. The expression of PGC1α, a transcriptional coactivator, is increased in the skeletal muscle during exercise. PGC1α activates branched-chain amino acid (BCAA) metabolism and is used for energy in the tricarboxylic acid (TCA) cycle. Leucine, a BCAA, and its metabolite, β-hydroxy-β-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. The metabolite of valine (another BCAA), β-aminoisobutyric acid (BAIBA), is increased by exercise, is secreted by the skeletal muscle, and acts on other tissues, such as white adipose tissue, to increase energy expenditure. In addition, several amino acid-related molecules reportedly activate skeletal muscle function. Oral 5-aminolevulinic acid (ALA) supplementation can protect against mild hyperglycemia and help prevent type 2 diabetes. β-alanine levels are decreased in the skeletal muscles of aged mice. β-alanine supplementation increased the physical performance and improved the executive function induced by endurance exercise in middle-aged individuals. Further studies focusing on the effects of amino acids and their metabolites on skeletal muscle function will provide data essential for the production of food supplements for older adults, athletes, and individuals with metabolic diseases. Full article
(This article belongs to the Special Issue Amino Acids and Health Effects)
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<p>Metabolic changes in the skeletal muscle during exercise and amino acid-mediated interorgan effects. PGC1α expression in the skeletal muscle is increased by exercise. Increased PGC1<span class="html-italic">α</span> activates BCAA metabolism, fatty acid oxidation, and the TCA cycle and increases energy usage [<a href="#B20-nutrients-12-00261" class="html-bibr">20</a>,<a href="#B24-nutrients-12-00261" class="html-bibr">24</a>]. BCAA degradation leads to the formation of ammonia by-products. FOXO1 increases glutamine synthetase (adds ammonia to glutamic acid), resulting in the elimination of ammonia from the liver (urea cycle) [<a href="#B23-nutrients-12-00261" class="html-bibr">23</a>]. In turn, exercise-induced PGC1<span class="html-italic">α</span> increases BAIBA, GABA, and arginine levels in the skeletal muscle [<a href="#B24-nutrients-12-00261" class="html-bibr">24</a>]. BAIBA secreted from the skeletal muscle causes browning of white adipose tissue and increases thermogenesis [<a href="#B27-nutrients-12-00261" class="html-bibr">27</a>]. GABA and arginine-derived NO may act on blood vessels and improve blood flow. Thus, in terms of preventing metabolic diseases, myokines are likely to be important, as myokines mediate the signaling of the favorable effects of exercise from the skeletal muscle to other organs. Ingestion of these amino acids as supplemental foods may improve human health. PGC1<span class="html-italic">α</span>, peroxisome proliferator-activated receptor <span class="html-italic">γ</span> coactivator 1-<span class="html-italic">α</span>; BCAA, branched-chain amino acid; TCA cycle, tricarboxylic acid cycle; FOXO1, forkhead box protein O1; Gln, glutamine; BAIBA, <span class="html-italic">β</span>-aminoisobutyric acid; GABA, <span class="html-italic">γ</span>-aminobutyric acid; NO, nitric oxide.</p>
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<p>mTORC1 is activated by amino acids, such as leucine, HMB, and arginine. mTORC1 phosphorylates substrates, such as 4EBP and S6K, and increases protein synthesis. Moreover, in the presence of these amino acids, mTORC1 suppresses starvation signals, such as autophagy. Amino acids (leucine, HMB, and arginine) can activate Akt, leading to mTORC1 activation and FOXO1 suppression [<a href="#B28-nutrients-12-00261" class="html-bibr">28</a>,<a href="#B34-nutrients-12-00261" class="html-bibr">34</a>,<a href="#B35-nutrients-12-00261" class="html-bibr">35</a>,<a href="#B36-nutrients-12-00261" class="html-bibr">36</a>]. FOXO1 is a transcription factor that induces muscle atrophy. Suppression of FOXO1 transcriptional activity leads to decreased autophagy. Leucine interacts with Sestrin 1 or Sestrin 2 [<a href="#B5-nutrients-12-00261" class="html-bibr">5</a>,<a href="#B32-nutrients-12-00261" class="html-bibr">32</a>], and arginine interacts with CASTOR1 and activates mTORC1 [<a href="#B33-nutrients-12-00261" class="html-bibr">33</a>]. The nature of the molecules involved in the amino acid-mediated pathway (e.g., the differences among leucine, HMB, and arginine) warrants further clarification. Leu, leucine; HMB, <span class="html-italic">β</span>-hydroxy-<span class="html-italic">β</span>-methylbutyrate; Arg, arginine; mTORC1, mammalian target of rapamycin complex 1; CASTOR1, cytosolic arginine sensor for mTORC1 subunit 1; FOXO1, forkhead box protein O1; S6K, S6 kinase; eIF4E, eukaryotic initiation factor 4E; 4EBP, eIF4E-binding protein; ULK1, unc-51 like autophagy activating kinase; BNIP3, Bcl-2 19 kDa interacting protein 3; MuRF1, muscle RING-finger protein-1.</p>
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<p>Metabolomic analysis of the skeletal muscles of young and aged mice [<a href="#B59-nutrients-12-00261" class="html-bibr">59</a>]. Aged muscle exhibited atrophy, especially in fast-twitch fibers (white fibers), which was accompanied by decreased glycolytic metabolism. Increases in the levels of neurotransmitters (serotonin and histamine) were observed, which may indicate (or explain) muscle injury and pain in aged muscle. Carboxymethyllysine, which is an AGE product, also increased in aged muscle, whereas <span class="html-italic">β</span>-alanine markedly decreased. Supplementation with <span class="html-italic">β</span>-alanine may improve the muscle function in sarcopenia. AGE, advanced glycation end product.</p>
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11 pages, 1059 KiB  
Article
Dietary Daily Sodium Intake Lower than 1500 mg Is Associated with Inadequately Low Intake of Calorie, Protein, Iron, Zinc and Vitamin B1 in Patients on Chronic Hemodialysis
by Maurizio Bossola, Enrico Di Stasio, Antonella Viola, Stefano Cenerelli, Alessandra Leo, Stefano Santarelli and Tania Monteburini
Nutrients 2020, 12(1), 260; https://doi.org/10.3390/nu12010260 - 19 Jan 2020
Cited by 14 | Viewed by 4274
Abstract
Background: To measure daily sodium intake in patients on chronic hemodialysis and to compare the intake of nutrients, minerals, trace elements, and vitamins in patients who had a daily sodium intake below or above the value of 1500 mg recommended by the American [...] Read more.
Background: To measure daily sodium intake in patients on chronic hemodialysis and to compare the intake of nutrients, minerals, trace elements, and vitamins in patients who had a daily sodium intake below or above the value of 1500 mg recommended by the American Heart Association. Methods: Dietary intake was recorded for 3 days by means of 3-day diet diaries in prevalent patients on chronic hemodialysis. Each patient was instructed by a dietitian on how to fill the diary, which was subsequently signed by a next of kin. Results: We studied 127 patients. Mean sodium intake (mg) was 1295.9 ± 812.3. Eighty-seven (68.5%) patients had a daily sodium intake <1500 mg (group 1) and 40 (31.5%) ≥ 1500 mg (group 2). Correlation between daily sodium intake and daily calorie intake was significant (r = 0.474 [0.327 to 0.599]; p < 0.0001). Daily calorie intake (kcal/kg/day) was lower in group 1 (21.1 ± 6.6; p = 0.0001) than in group 2 (27.1 ± 10.4). Correlation between daily sodium intake and daily protein intake was significant (r = 0.530 [0.392 to 0.644]; p < 0.0001). The daily protein intake (grams/kg/day) was lower in group 1 (0.823 ± 0.275; p = 0.0003) than in group 2 (1.061 ± 0.419). Daily intake of magnesium, copper, iron, zinc, and selenium was significantly lower in group 1 than in group 2. Daily intake of vitamin A, B2, B3, and C did not differ significantly between group 1 and group 2. Daily intake of vitamin B1 was significantly lower in group 1 than in group 2. Significantly lower was, in group 1 than in group 2, the percentage of patients within the target value with regard to intake of calories (11.5% vs. 37.5%; p = 0.001) and proteins (9.2% vs. 27.5%; p = 0.015) as well as of iron (23% vs. 45%; p = 0.020), zinc (13.8% vs. 53.8%; p = 0.008) and vitamin B1 (8.1% vs. 50%; p < 0.001). Conclusion: A low daily intake of sodium is associated with an inadequately low intake of calorie, proteins, minerals, trace elements, and vitamin B1. Nutritional counselling aimed to reduce the intake of sodium in patients on chronic hemodialysis should not disregard an adequate intake of macro- and micronutrients, otherwise the risk of malnutrition is high. Full article
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<p>Correlation between daily sodium intake and daily calorie intake. <span class="html-italic">r</span> = 0.474 [0.327–0.599]; <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Correlation between daily sodium intake and daily protein calorie intake. <span class="html-italic">r</span> = 0.530 [0.392–0.644]; <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Correlation between daily sodium intake and daily vitamin B1. <span class="html-italic">r</span> = 0.763 [0.679 to 0.827]; <span class="html-italic">p</span> &lt; 0.0001.</p>
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84 pages, 3660 KiB  
Review
Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence
by Sok Kuan Wong, Yusof Kamisah, Norazlina Mohamed, Norliza Muhammad, Norliana Masbah, Nur Azlina Mohd Fahami, Isa Naina Mohamed, Ahmad Nazun Shuid, Qodriyah Mohd Saad, Azman Abdullah, Nur-Vaizura Mohamad, Nurul’ Izzah Ibrahim, Kok-Lun Pang, Yoke Yue Chow, Benjamin Ka Seng Thong, Shaanthana Subramaniam, Chin Yi Chan, Soelaiman Ima-Nirwana and Kok-Yong Chin
Nutrients 2020, 12(1), 259; https://doi.org/10.3390/nu12010259 - 19 Jan 2020
Cited by 49 | Viewed by 9634
Abstract
Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, [...] Read more.
Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials. Full article
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<p>Effects of T3 on lipid metabolism.</p>
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<p>Cardioprotective effects of T3.</p>
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<p>Effects of T3 on cerebrovascular diseases.</p>
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<p>Bone-protecting property of T3.</p>
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<p>Effects of T3 on muscle health.</p>
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<p>Effects of T3 on peptic ulcer.</p>
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<p>Neuroprotective effect of T3 on Parkinson’s disease.</p>
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<p>Effects of T3 on Alzheimer’s disease. Solid lines represent advantageous effects of T3 while the dotted lines represent possible harmful effects of T3.</p>
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<p>Effects of T3 on wound healing.</p>
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<p>Beneficial effects of T3 on obesity and diabetes.</p>
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<p>Anti-cancer mechanism of T3.</p>
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17 pages, 536 KiB  
Article
Predictors of Early Introduction of Core and Discretionary Foods in Australian Infants—Results from HSHK Birth Cohort Study
by Narendar Manohar, Andrew Hayen, Sameer Bhole and Amit Arora
Nutrients 2020, 12(1), 258; https://doi.org/10.3390/nu12010258 - 19 Jan 2020
Cited by 10 | Viewed by 5112
Abstract
Early introduction of complementary foods can have a detrimental impact on children’s long-term health. This study examined the timing and determinants of early introduction of core and discretionary foods among infants in Sydney, Australia. Mothers (n = 1035) from an ongoing population-based [...] Read more.
Early introduction of complementary foods can have a detrimental impact on children’s long-term health. This study examined the timing and determinants of early introduction of core and discretionary foods among infants in Sydney, Australia. Mothers (n = 1035) from an ongoing population-based birth cohort study were interviewed at 8, 17, 34 and 52 weeks postpartum. The outcome was ‘age at which particular core and discretionary food items were first introduced’. Multivariable logistic regression models were used to investigate family and infant-related determinants of early introduction of core (<17 weeks of age) and discretionary foods (<52 weeks of age). Of the 934 mother-infant dyads interviewed, 12% (n = 113) of infants were introduced core foods before 17 weeks of age (median: 22). Mothers working part-time (adjusted odds ratio (OR): 3.42, 95% confidence interval (CI): 1.54–7.62) and those exclusively formula-feeding their babies at four-weeks postpartum (adjusted OR 3.26, 95% CI: 1.99–5.33) were most likely to introduce core foods early. Ninety-five percent (n = 858) of infants were introduced discretionary foods before 52 weeks of age (median: 28). Low socio-economic status was significantly associated with early introduction of discretionary foods (adjusted OR: 3.72, 95% CI: 1.17–11.78). Compliance with infant feeding guidelines related to core foods was better; however, discretionary foods were introduced early in most infants. Full article
(This article belongs to the Special Issue Healthy Diet and Lifestyles in the Pediatric Population)
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<p>The distribution of age at which core and discretionary foods were first introduced.</p>
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26 pages, 7857 KiB  
Article
The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells
by Małgorzata Zakłos-Szyda and Grażyna Budryn
Nutrients 2020, 12(1), 257; https://doi.org/10.3390/nu12010257 - 19 Jan 2020
Cited by 16 | Viewed by 6864
Abstract
Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many [...] Read more.
Uncontrolled growth and migration and invasion abilities are common for cancer cells in malignant tumors with low therapeutic effectiveness and high mortality and morbidity. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor suppressive activities in many cancers. Phytoestrogens’ structural resemblance to 17 β-estradiol allows their binding to ERβ isoform predominantly, and therefore, expression of genes connected with elevated proliferation, motility and invasiveness of cancer cells may be downregulated. Among polyphenolic compounds with phytoestrogenic activity, there are isoflavones from Trifolium pratense L. (red clover) sprouts, containing high amounts of formononetin and biochanin A and their glycosides. To determine the source of the most biologically active isoflavones, we obtained four extracts from sprouts before and after their lactic fermentation and/or β-glucosidase treatment. Our previous results of ITC (isothermal titration calorimetry) modelling and a docking simulation showed clover isoflavones’ affinity to ERβ binding, which may downregulate cancer cell proliferation and migration. Thus, the biological activity of T. pratense sprouts’ extracts was checked under in vitro conditions against highly invasive human breast cancer cell line MDA-MB-231 and non-invasive human breast cancer cell line MCF-7 cells. To compare extracts’ activities acquired for cancer cells with those activities against normal cells, as a third model we choose human umbilical vein endothelial cells (HUVEC), which, due to their migration abilities, are involved in blood vessel formation. Extracts obtained from fermented sprouts at IC0 dosages were able to inhibit migration of breast cancer cells through their influence on intracellular ROS generation; membrane stiffening; adhesion; regulation of MMP-9, N-cadherin and E-cadherin at transcriptional level; or VEGF secretion. Simultaneously, isolated phenolics revealed no toxicity against normal HUVEC cells. In the manuscript, we proposed a preliminary mechanism accounting for the in vitro activity of Trifolium pratense L. isoflavones. In this manner, T. pratense sprouts, especially after their lactic fermentation, can be considered a potent source of biological active phytoestrogens and a dietary supplement with anti-cancer and anti-invasion properties. Full article
(This article belongs to the Special Issue Isoflavone Intake and Human Health)
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<p>The influence of <span class="html-italic">T. pratense</span> extracts on MDA-MB-231 (<b>A</b>), MCF-7 (<b>B</b>) and HUVEC (<b>C</b>) cells’ metabolic activity determined by PrestoBlue assay after 48 h exposure to CU (sprouts polyphenolic extract), CUH (sprouts polyphenolic extract after hydrolysis), CUF (fermented sprouts polyphenolic extract) and CUFH (fermented sprouts polyphenolic extract after hydrolysis). Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments (<span class="html-italic">n</span> ≥ 16).</p>
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<p>The influence of 48 h of exposure of <span class="html-italic">T. pratense</span> extracts on phosphatidylserine externalization on the outer membrane leaflet of apoptotic cells and membrane permeabilization detected with Annexin-V in MDA-MB-231 (<b>A</b>), MCF-7 (<b>B</b>) and HUVEC (<b>C</b>) cells. Values are means ± standard deviations, <span class="html-italic">n</span> ≥ 6; statistical significance was calculated versus control cells (untreated); * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>The effect of <span class="html-italic">T. pratense</span> extracts on intracellular ROS generation analyzed by DCFH-DA assay after 48 h incubation with MDA-MB-231 (<b>A</b>), MCF-7 (<b>B</b>) and HUVEC (<b>C</b>) cells. Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p>Changes in cell membrane fluidity expressed as values of generalized polarization (GP) for Laurdan probe after incubation of cells with <span class="html-italic">T. pratense</span> at IC<sub>0</sub> (<b>A</b>). The effect of <span class="html-italic">T. pratense</span> extracts on mitochondrial membrane potential was determined with JC-1 probe. As a positive control for depolarization, carbonyl cyanide m-chlorophenyl hydrazine (CCCP) (50 μM) was used (<b>B</b>). control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); * <span class="html-italic">p</span> ≤ 0.05, *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p>The influence of 48 h of exposure of <span class="html-italic">T. pratense</span> extracts on the migration (<b>A</b>) and wound healing (<b>B</b>) of MDA-MB-231 cells. Migration rates of MDA-MB-231 cells incubated with extracts at IC<sub>0</sub> dosages into the free detection zones were photographed (×8) (<b>C</b>). Cell adhesion to the substrate was measured after staining with crystal violet; randomly chosen fields were photographed at ×200 (<b>D</b>). Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); ** <span class="html-italic">p</span> ≤ 0.01, *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p>The influence of 48 h of exposure of <span class="html-italic">T. pratense</span> extracts on the wound healing (<b>A</b>) and migration (<b>B</b>) of MCF-7 cells. Migration rates of MCF-7 cells incubated with extracts at IC<sub>0</sub> dosages into the free detection zones were photographed (×8) (<b>C</b>). Cell adhesion to the substrate was measured after staining with crystal violet; randomly chosen fields were photographed at ×200 (<b>D</b>). Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); ** <span class="html-italic">p</span> ≤ 0.01, *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p>The influence of 48 h of exposure of <span class="html-italic">T. pratense</span> extracts on wound healing (<b>A</b>) and migration (<b>B</b>) of HUVEC cells. Migration rates of HUVEC cells incubated with extracts at IC<sub>0</sub> dosages into the free detection zones were photographed (×8) (<b>C</b>). Cells adhesion to the substrate was measured after staining with crystal violet; randomly chosen fields were photographed at ×200 (<b>D</b>). Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations from at least three independent experiments; statistical significance was calculated versus control cells (untreated); * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01, *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p>The influence of 48 h of exposure to <span class="html-italic">T. pratense</span> extracts on the expression of genes in MDA-MB-231 (<b>A</b>), MCF-7 (<b>B</b>) and HUVEC (<b>C</b>) cells. The expression levels of <span class="html-italic">MMP-9</span>, <span class="html-italic">MMM-2</span>, <span class="html-italic">ERα</span>, <span class="html-italic">ERβ</span>, <span class="html-italic">E-cadherin</span>, and <span class="html-italic">N-cadherin</span> were quantified by real-time PCR and normalized using hypoxanthine phosphoribosyltransferase 1 (<span class="html-italic">HPRT1</span>) as a reference gene. Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations, <span class="html-italic">n</span> ≥ 3; statistical significance was calculated versus control cells (untreated) * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01.</p>
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<p>Analysis of relative ERα and ERβ expressions at the mRNA (<b>A</b>) and protein levels (<b>B</b>) in MDA-MB-231 and MCF-7 cells (samples were calibrated by MDA-MB-231 ERβ). The influence of 48 h of exposure to <span class="html-italic">T. pratense</span> extracts on the expression of estrogen receptor proteins in MDA-MB-231 (<b>C</b>) and MCF-7 (<b>D</b>) cells—bands of western blot representative experiment. The expression levels of ERα and ERβ were quantified by western blot and normalized using β actin as a reference protein. Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations, <span class="html-italic">n</span> = 3. (<b>E</b>) Relative proliferative effects (RPE) of extracts and 17 <span class="html-italic">β</span>-estradiol on proliferative estrogenic activity (RPE) properties according to E-screen assay (<span class="html-italic">n</span> ≥ 8).</p>
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<p>The influence of 48 h of exposure of <span class="html-italic">T. pratense</span> extracts at IC<sub>0</sub> dosages on VEGF secretion and <span class="html-italic">VEGF</span> mRNA level in MDA-MB-231 (<b>A</b>), MCF-7 (<b>B</b>) and HUVEC cells (<b>C</b>). Control cells were not exposed to any compound but the vehicle; values are means ± standard deviations, <span class="html-italic">n</span> = 3; statistical significance was calculated versus control cells (untreated) * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01, *** <span class="html-italic">p</span> ≤ 0.001.</p>
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<p><span class="html-italic">Trifolium pratense</span> isoflavones as modulators of cell migration—the proposed mechanism of action. They possess cytoprotective activity against ROS generation, stiffen cellular membrane, induce apoptotic type cell death and influence expression of <span class="html-italic">MMP9</span> and <span class="html-italic">VEGF</span>. ERα/β—estrogen receptor α/β; ERE—estrogen responsive element; MMP9—matrix metalloproteinase 9; VEGF—vascular endothelial growth factor.</p>
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9 pages, 938 KiB  
Article
Saliva Secretion and Swallowing—The Impact of Different Types of Food and Drink on Subsequent Intake
by Catherina Bozorgi, Celina Holleufer and Karin Wendin
Nutrients 2020, 12(1), 256; https://doi.org/10.3390/nu12010256 - 19 Jan 2020
Cited by 15 | Viewed by 7162
Abstract
The oral processing of food is important for eating and digestion in order to gain energy and nutrients. Due to disease, injury, or aging, individuals may experience difficulties in this process. These difficulties often lead to dysphagia, which is associated with malnutrition. Thus, [...] Read more.
The oral processing of food is important for eating and digestion in order to gain energy and nutrients. Due to disease, injury, or aging, individuals may experience difficulties in this process. These difficulties often lead to dysphagia, which is associated with malnutrition. Thus, it is of importance to find solutions and strategies to enable food intake. It is well known that sour and/or carbonated foods and drinks increase saliva secretion and trigger the swallowing reflex. However, knowledge regarding how subsequent food intake is impacted is lacking. The aim of this study was to clarify whether sour and/or carbonated foods and drinks had subsequent impacts on swallowing function. Twelve healthy participants evaluated eleven foods and drinks in terms of their ability to increase saliva production and ease the swallowing of subsequent food. Results showed that sourness and carbonation had positive impacts on saliva secretion and swallowing. No correlation was found between the pH/sourness of the foods and the ease of swallowing them. It was concluded that the ingestion of cherry tomatoes, natural yoghurt, and, in particular, citrus juice made swallowing of a neutral cracker easier. These results may be used to increase food intake among dysphagia patients. Full article
(This article belongs to the Special Issue Nutrition for Older Persons' Health)
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<p>Questions 1a and 1b formed the baseline for questions 2a–2e. These questions were repeated in all eleven questionnaires, i.e., for each product the subjects consumed. The participants made a mark on a scale measuring 12 cm in length.</p>
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<p>Ease of swallowing test foods compared to the baseline cracker. The red bars indicate a significant difference from the baseline, <span class="html-italic">p</span> ≤ 0.05.</p>
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<p>Perceived amount of saliva for test foods compared to the baseline cracker. The red bars indicate a significant difference from the baseline, <span class="html-italic">p</span> ≤ 0.05.</p>
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15 pages, 914 KiB  
Article
Effects of Lactobacillus plantarum Q180 on Postprandial Lipid Levels and Intestinal Environment: A Double-Blind, Randomized, Placebo-Controlled, Parallel Trial
by Ye Eun Park, Min Seo Kim, Kyung Won Shim, You-Il Kim, Jaeryang Chu, Byoung-Kook Kim, In Suk Choi and Ji Yeon Kim
Nutrients 2020, 12(1), 255; https://doi.org/10.3390/nu12010255 - 19 Jan 2020
Cited by 26 | Viewed by 6817
Abstract
Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal [...] Read more.
Probiotics can improve the intestinal environment by enhancing beneficial bacteria to potentially regulate lipid levels; however, the underlying mechanisms remain unclear. The aim of this study was to investigate the effect of Lactobacillus plantarum Q180 (LPQ180) on postprandial lipid metabolism and the intestinal microbiome environment from a clinical perspective. A double-blind, randomized, placebo-controlled study was conducted including 70 participants of both sexes, 20 years of age and older, with healthy blood triacylglyceride (TG) levels below 200 mg/dL. Treatment with LPQ180 for 12 weeks significantly decreased LDL-cholesterol (p = 0.042) and apolipoprotein (Apo)B-100 (p = 0.003) levels, and decreased postprandial maximum concentrations (Cmax) and areas under the curve (AUC) of TG, chylomicron TG, ApoB-48, and ApoB-100. LPQ180 treatment significantly decreased total indole and phenol levels (p = 0.019). In addition, there was a negative correlation between baseline microbiota abundance and lipid marker change, which was negatively correlated with metabolites. This study suggests that LPQ180 might be developed as a functional ingredient to help maintain healthy postprandial lipid levels through modulating gut environment. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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<p>Flow chart of registered participants for the clinical trial.</p>
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<p>Changes in the intestinal microflora: (<b>A</b>) intestinal flora diversity represented by Shannon index (Alpha-diversity); (<b>B</b>) distance analysis between microbial communities by group (NMDS: Non-metric Multidimensional Scaling); (<b>C</b>) 12-week change in the placebo and LPQ180 groups of Actinobacteria, the upper level of <span class="html-italic">Eggerthella</span> spp.; and (<b>D</b>) microbial community significantly changing between Week 0 and Week 12 at genus level (<span class="html-italic">Eggerthella</span> spp.).</p>
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12 pages, 1191 KiB  
Article
Essential Amino Acid Supplement Lowers Intrahepatic Lipid despite Excess Alcohol Consumption
by Melynda S. Coker, Kaylee R. Ladd, Jimin Kim, Carl J. Murphy, Ryan DeCort, Bradley R. Newcomer, Robert R. Wolfe and Robert H. Coker
Nutrients 2020, 12(1), 254; https://doi.org/10.3390/nu12010254 - 19 Jan 2020
Cited by 3 | Viewed by 7871
Abstract
Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in [...] Read more.
Excess alcohol consumption is a top risk factor for death and disability. Fatty liver will likely develop and the risk of liver disease increases. We have previously demonstrated that an essential amino acid supplement (EAAS) improved protein synthesis and reduced intrahepatic lipid in the elderly. The purpose of this exploratory pilot study was to initiate the evaluation of EAAS on intrahepatic lipid (IHL), body composition, and blood lipids in individuals with mild to moderate alcohol use disorder (AUD). Following consent, determination of eligibility, and medical screening, 25 participants (18 males at 38 ± 15 years/age and 7 females at 34 ± 18 years/age) were enrolled and randomly assigned to one of two dosages: a low dose (LD: 8 g of EAAS twice/day (BID)) or high dose (HD: 13 g of EAAS BID). Five of the twenty-five enrolled participants dropped out of the intervention. Both groups consumed the supplement BID for 4 weeks. Pre- and post-EAAS administration, IHL was determined using magnetic resonance imaging/spectroscopy, body composition was analyzed using dual-energy X-ray absorptiometry, and blood parameters were measured by LabCorp. T-tests were used for statistical analysis and considered significant at p < 0.05. While there was no significant change in IHL in the LD group, there was a significant 23% reduction in IHL in the HD group (p = 0.02). Fat mass, lean tissue mass, bone mineral content, and blood lipids were not altered. Post-EAAS phosphatidylethanol was elevated and remained unchanged in LD at 407 ± 141 ng/mL and HD at 429 ± 196 ng/mL, indicating chronic and excess alcohol consumption. The HD of the proprietary EAAS formulation consumed BID seemed to lower IHL in individuals with mild to moderate AUD. We suggest that further studies in a larger cohort be conducted to more completely address this important area of investigation. Full article
(This article belongs to the Special Issue Nutrition, Metabolic Status, and Body Composition)
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<p>Study timeline.</p>
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<p>(<b>A</b>) MRI of liver detailing the location of voxel and (<b>B</b>) an example of 1-H spectroscopy derived measurement of intrahepatic lipid.</p>
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<p>Intrahepatic lipid in low dose (LD) and high dose (HD) pre- and post-essential amino acid supplement (EAAS). * Represents a significant difference between pre- and post-EAAS (<span class="html-italic">p</span> = 0.02).</p>
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11 pages, 1428 KiB  
Article
Socio-Economic Inequalities in Child Stunting Reduction in Sub-Saharan Africa
by Kaleab Baye, Arnaud Laillou and Stanley Chitweke
Nutrients 2020, 12(1), 253; https://doi.org/10.3390/nu12010253 - 18 Jan 2020
Cited by 27 | Viewed by 5289
Abstract
Stunting in children less than five years of age is widespread in Sub-Saharan Africa. We aimed to: (i) evaluate how the prevalence of stunting has changed by socio-economic status and rural/urban residence, and (ii) assess inequalities in children’s diet quality and access to [...] Read more.
Stunting in children less than five years of age is widespread in Sub-Saharan Africa. We aimed to: (i) evaluate how the prevalence of stunting has changed by socio-economic status and rural/urban residence, and (ii) assess inequalities in children’s diet quality and access to maternal and child health care. We used data from nationally representative demographic and health- and multiple indicator cluster-surveys (DHS and MICS) to disaggregate the stunting prevalence by wealth quintile and rural/urban residence. The composite coverage index (CCI) reflecting weighed coverage of eight preventive and curative Reproductive, Maternal, Neonatal, and Child Health (RMNCH) interventions was used as a proxy for access to health care, and Minimum Dietary Diversity Score (MDDS) was used as a proxy for child diet quality. Stunting significantly decreased over the past decade, and reductions were faster for the most disadvantaged groups (rural and poorest wealth quintile), but in only 50% of the countries studied. Progress in reducing stunting has not been accompanied by improved equity as inequalities in MDDS (p < 0.01) and CCI (p < 0.001) persist by wealth quintile and rural-urban residence. Aligning food- and health-systems’ interventions is needed to accelerate stunting reduction more equitably. Full article
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<p>Average stunting reductions in regions with Low- and Middle-Income Countries (LMIC). Authors’ graph using UNICEF-WHO-The World Bank: joint malnutrition estimates [<a href="#B2-nutrients-12-00253" class="html-bibr">2</a>].</p>
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<p>Change of stunting prevalence in rural relative to urban residence (rural-urban) over 1998–2008 to 2009–2018 periods. The graph presents excess changes relative to urban residence; negative values are desirable outcomes as it means faster changes in stunting are happening in the most disadvantaged group.</p>
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<p>Change of stunting prevalence in the poorest relative to the wealthiest quintile (poorest-richest) over 1998–2008 to 2009–2018 periods. The graph presents excess changes relative to the wealthiest quintile; negative values are desirable outcomes as it means faster changes in stunting has happened in the most disadvantaged group.</p>
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<p>Stunting prevalence by rural/urban residence. Data is from the most recent demographic and health surveys. Dots show stunting prevalence estimates for children younger than five years of age residing in rural (navy blue) and urban (orange) residence.</p>
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<p>Stunting prevalence by wealth quintile. Dots represent estimated stunting prevalence for the poorest, second, middle, fourth, and the highest wealth quintile.</p>
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<p>Coverage index of eight reproductive maternal neonatal and child interventions along the continuum of care (<b>A</b>) and proportion of children meeting minimum dietary diversity score (<b>B</b>) by rural/urban and poorest/richest quintile (<span class="html-italic">n</span> = 34). The boxplots present country level analyses of the latest round of DHS or MICS. Statistical tests are from independent <span class="html-italic">t</span>-test comparing prevalence in the poorest to the richest quintiles and rural to urban residents.</p>
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11 pages, 444 KiB  
Article
Small-Scale Livestock Production in Nepal Is Directly Associated with Children’s Increased Intakes of Eggs and Dairy, But Not Meat
by Elena T. Broaddus-Shea, Swetha Manohar, Andrew L. Thorne-Lyman, Shiva Bhandari, Bareng A. S. Nonyane, Peter J. Winch and Keith P. West, Jr.
Nutrients 2020, 12(1), 252; https://doi.org/10.3390/nu12010252 - 18 Jan 2020
Cited by 19 | Viewed by 4601
Abstract
Animal source foods (ASF) provide nutrients essential to child growth and development yet remain infrequently consumed in rural Nepal. Agriculture and nutrition programs aim to increase ASF intake among children through small-scale animal husbandry projects. The relationship between livestock ownership and children’s consumption [...] Read more.
Animal source foods (ASF) provide nutrients essential to child growth and development yet remain infrequently consumed in rural Nepal. Agriculture and nutrition programs aim to increase ASF intake among children through small-scale animal husbandry projects. The relationship between livestock ownership and children’s consumption of ASF, however, is not well established. This study examined associations between livestock ownership and the frequency with which Nepali children consume eggs, dairy, and meat. We analyzed longitudinal 7-day food frequency data from sentinel surveillance sites of the Policy and Science of Health, Agriculture and Nutrition (PoSHAN) study. Data consisted of surveys from 485 Nepali farming households conducted twice per year for two years (a total of 1449 surveys). We used negative binomial regression analysis to examine the association between the number of cattle, poultry, and meat animals (small livestock) owned and children’s weekly dairy, egg, and meat intakes, respectively, adjusting for household expenditure on each food type, mother’s education level, caste/ethnicity, agroecological region, season, and child age and sex. We calculated predicted marginal values based on model estimates. Children consumed dairy 1.4 (95% CI 1.1–2.0), 2.3 (1.7–3.0) and 3.0 (2.1–4.2) more times per week in households owning 1, 2–4 and >4 cattle, respectively, compared to children in households without cattle. Children consumed eggs 2.8 (2.1–3.7) more times per week in households owning 1 or 2 chickens compared to children in households without chickens. Child intake of meat was higher only in households owning more than seven meat animals. Children’s intakes of dairy, eggs, and meat rose with household expenditure on these foods. Small-scale animal production may be an effective strategy for increasing children’s consumption of eggs and dairy, but not meat. Increasing household ability to access ASF via purchasing appears to be an important approach for raising children’s intakes of all three food types. Full article
(This article belongs to the Special Issue Food Variety and Nutrition Status)
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<p>Predicted average weekly consumption frequency (with 95% confidence intervals) of eggs, meat, and dairy at different levels of animal production and expenditure on animal-source foods, adjusting for all other covariates (mother’s education, caste/ethnicity, region, season, child sex, child age). Predictions were generated using negative binomial model estimates presented in <a href="#nutrients-12-00252-t002" class="html-table">Table 2</a>.</p>
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9 pages, 588 KiB  
Article
Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC®
by Mayssa Hachem, Houda Nacir, Madeleine Picq, Mounir Belkouch, Nathalie Bernoud-Hubac, Anthony Windust, Laure Meiller, Valerie Sauvinet, Nathalie Feugier, Stephanie Lambert-Porcheron, Martine Laville and Michel Lagarde
Nutrients 2020, 12(1), 251; https://doi.org/10.3390/nu12010251 - 18 Jan 2020
Cited by 17 | Viewed by 4704
Abstract
AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration [...] Read more.
AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion. Full article
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<p><sup>13</sup>C-DHA in plasma phospholipids from AceDoPC compared to TAG-DHA after 50 mg DHA intake in both esterified forms, at different times post-intake (<b>A</b>). Results are expressed in pmol of <sup>13</sup>C-DHA per mL of plasma, presented as means ± SEM from three values. (<b>B</b>) represents area under curves (AUC) from <a href="#nutrients-12-00251-f001" class="html-fig">Figure 1</a>A. Stars indicate significant differences within each time, according to the student <span class="html-italic">t</span> test.</p>
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<p><sup>13</sup>C-DHA in red cell phospholipids after intake of <sup>13</sup>C-DHA esterified in either AceDoPC or TAG. Fifty milligrams of <sup>13</sup>C-DHA source were ingested, and blood samples collected at the different times shown in figures. PE &amp; PC were separated as described in Materials &amp; Methods. Results are expressed in pmol of <sup>13</sup>C-DHA per mL of blood, presented as ± SEM from three values. (<b>A</b>) relates to <sup>13</sup>C-DHA incorporation into red cell PC+PE. (<b>B</b>,<b>C</b>) relate to separate phospholipids PC and PE, respectively.</p>
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18 pages, 847 KiB  
Review
Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy
by Inês Preguiça, André Alves, Sara Nunes, Pedro Gomes, Rosa Fernandes, Sofia D. Viana and Flávio Reis
Nutrients 2020, 12(1), 250; https://doi.org/10.3390/nu12010250 - 18 Jan 2020
Cited by 43 | Viewed by 8590
Abstract
Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high [...] Read more.
Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions. Full article
(This article belongs to the Special Issue Nutrition for Eye Health)
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<p>Comparative criteria for human and rodent models of diabetic peripheral neuropathy, retinopathy, and nephropathy. (NCS, nerve conduction studies; IENFD, intraepidermal nerve fibers density; CCM, corneal confocal microscopy; ACR, albumin-to-creatinine ratio; DR, diabetic retinopathy; GFR, glomerular filtration rate).</p>
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18 pages, 19203 KiB  
Article
Fermented Morinda citrifolia (Noni) Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice through Modulating Immune Balance and Skin Barrier Function
by Sung Ho Kim, Geum Su Seong and Se Young Choung
Nutrients 2020, 12(1), 249; https://doi.org/10.3390/nu12010249 - 18 Jan 2020
Cited by 41 | Viewed by 9649
Abstract
Morinda citrifolia, a fruit generally known as “Noni”, has been traditionally used in parts of East Asia to relieve inflammatory diseases. Although several studies using noni have been reported, the effect of fermented Morinda citrifolia (F.NONI) on atopic dermatitis (AD) has not [...] Read more.
Morinda citrifolia, a fruit generally known as “Noni”, has been traditionally used in parts of East Asia to relieve inflammatory diseases. Although several studies using noni have been reported, the effect of fermented Morinda citrifolia (F.NONI) on atopic dermatitis (AD) has not been investigated. Thus, we aimed to investigate the improving effect of F.NONI treatment on AD-like skin lesions and elucidate molecular mechanisms. F.NONI was prepared by the fermentation of noni fruit with probiotics and then extracted. F.NONI was orally administrated to NC/Nga mice to evaluate its therapeutic effect on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral administration of F.NONI significantly alleviated AD lesions and symptoms such as dermatitis scores, ear thickness, scratching behavior, epidermal thickness, and infiltration of inflammatory cells (e.g., mast cells and eosinophils). In addition, F.NONI treatment reduced the levels of histamine, IgE and IgG1/IgG2a ratio, thymus and activation regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) in serum and beneficially modulated the expressions of Th1, Th2, Th17, and Th22-mediated cytokines in lesioned skin and splenocytes. Furthermore, the expressions of the skin barrier-related proteins including filaggrin (FLG), loricrin (LOR), involucrin (IVL), zonula occludens-1 (ZO-1), and occludin (OCC) were restored by F.NONI treatment. Taken together, these results suggest that F.NONI could be a therapeutic agent to attenuate AD-like skin lesions through modulating the immune balance and skin barrier function. Full article
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Figure 1

Figure 1
<p>Representative HPLC-UV chromatogram of noni and F.NONI. (<b>A</b>) Standard; (<b>B</b>) Noni extract; (<b>C</b>) F.NONI extract. The arrows represent deacetylasperulosidic acid (DAA) and asperulosidic acid (AA). (Standard DDA Rt: 18.78 ± 0.06 min; noni and F.NONI each 18.78 ± 0.08 and 18.79 ± 0.07 min. Standard AA Rt: 27.31 ± 0.05 min; noni and F.NONI each 27.32 ± 0.06 and 27.32 ± 0.07 min) AU: Absorption unit.</p>
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<p>Experimental procedure and effect of F.NONI on the clinical features of AD-like symptoms induced by DNCB in NC/Nga mice. (<b>A</b>) Schematic diagram of the experimental procedure for the induction of AD lesions and F.NONI treatment. (<b>B</b>) Photographic images of skin lesions in NC/Nga mice were taken on the last day of the experiment in the fourth week. (<b>C</b>) Clinical features in NC/Nga mice—(<b>a</b>) dermatitis score, (<b>b</b>) ear thickness, and (<b>c</b>) scratching behavior—were evaluated three times a week in the term of the administration of vehicle, prednisolone, and F.NONI. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 6). <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group; DNCB (2,4-dinitrochlorobenzene).</p>
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<p>Effect of F.NONI on DNCB-induced histological features of AD-like skin lesions in NC/Nga mice. (<b>A</b>) Representative dorsal skin images of histological examination (400x, scale bar = 100μm); (<b>a</b>) H&amp;E staining; the thicknesses of the epidermis are marked with bars, and infiltration of eosinophils is indicated by arrows; (<b>b</b>) toluidine blue staining; the infiltrations of mast cells are indicated by arrows. (<b>B</b>) The thicknesses of the epidermis were measured in the dorsal skin lesion and averaged. (<b>C</b>) The number of infiltrated inflammatory cells, (<b>a</b>) mast cells and (<b>b</b>) eosinophils, were measured in 1 mm<sup>2</sup> of a dorsal skin lesion and averaged (<span class="html-italic">n</span> = 6). The results were presented as mean ± SEM (<span class="html-italic">n</span> = 6). <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group.</p>
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<p>Effect of F.NONI on levels of AD-related cytokines and IgE in the serum of AD-induced NC/Nga mice. (<b>A</b>) Levels of IgE in serum; (<b>B</b>) levels of histamine in serum; (<b>C</b>) levels of TARC in serum; (<b>D</b>) levels of TSLP in serum. The sera of NC/Nga mice were collected on the last day of the experiment and measured using ELISA. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 6). <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group.</p>
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<p>Effect of F.NONI on AD-related cytokine secretion in the splenocytes of AD-induced NC/Nga mice. (<b>A</b>) Levels of (<b>a</b>) IL-4, (<b>b</b>) IL-5, (<b>c</b>) IL-13, (<b>d</b>) IL-31, and (<b>e</b>) IL-33 in the supernatant of splenocytes. (<b>B</b>) Levels of (<b>a</b>) IL-12 and (<b>b</b>) IFN-γ in the supernatant of splenocytes. (<b>C</b>) Levels of (<b>a</b>) IL-6, (<b>b</b>) IL-17, and (<b>c</b>) IL-22 in the supernatant of splenocytes. The splenocytes of NC/Nga mice were obtained on the last day of the experiment and responded to in vitro. Con-A stimulation for 72 h, then supernatant was measured using ELISA. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 5). <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group.</p>
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<p>Effect of F.NONI on gene expression of AD-related cytokines in the dorsal skin of AD induced NC/Nga mice. (<b>A</b>) Gene expression of (<b>a</b>) IL-4, (<b>b</b>) IL-5, (<b>c</b>) IL-13, (<b>d</b>) IL-31, (<b>e</b>) IL-33, and (<b>f</b>) TSLP. (<b>B</b>) Gene expression of (<b>a</b>) IL-12p40 and (<b>b</b>) IFN-γ. (<b>C</b>) Gene expression of (<b>a</b>) TNF-α, (<b>b</b>) IL-6, (<b>c</b>) IL-17A, and (<b>d</b>) IL-22. The total RNA was isolated from the dorsal skins of NC/Nga mice and analyzed by RT-qPCR and then normalized to GAPDH. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 5). <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group.</p>
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<p>Effect of F.NONI on skin barrier dysfunction in the dorsal skin of AD-induced NC/Nga mice. (<b>A</b>) Protein levels of FLG (34 kDa), LOR (26 kDa), IVL (68 kDa), OCC (59 kDa), ZO-1 (187 kDa), and ß-actin (43 kDa) were analyzed using Western immunoblotting. (<b>B</b>) The protein levels of (<b>a</b>) FLG, (<b>b</b>) LOR, (<b>c</b>) IVL, (<b>d</b>) OCC, and (<b>e</b>) ZO-1 were quantified by band density and normalized to ß-actin. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 4). (<b>C</b>) Gene expression levels of pro-FLG were analyzed in dorsal skin using RT-qPCR. The results were presented as mean ± SEM (<span class="html-italic">n</span> = 5); <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. normal, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control. Normal, untreated group; Control, atopic dermatitis induced by DNCB; PD, positive control (prednisolone 3 mg/kg) treated group; F.NONI (fermented <span class="html-italic">Morinda citrifolia</span> 250, 500, or 1000 mg/kg) treated group; FLG, filaggrin; LOR, loricrin; IVL, involucrin; ZO-1, zonula occludens-1; OCC, occludin; pro-FLG, pro-filaggrin.</p>
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15 pages, 327 KiB  
Article
Microencapsulated Tuna Oil Results in Higher Absorption of DHA in Toddlers
by Samaneh Ghasemi Fard, Su Peng Loh, Giovanni M. Turchini, Bo Wang, Glenn Elliott and Andrew J. Sinclair
Nutrients 2020, 12(1), 248; https://doi.org/10.3390/nu12010248 - 18 Jan 2020
Cited by 16 | Viewed by 6418
Abstract
Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving [...] Read more.
Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving the stability and bioavailability of DHA at levels akin to human breast milk. The aims of this study were (a) to investigate the bioavailability of microencapsulated omega-3 DHA formulations in healthy toddlers compared with high DHA fish oil for a one-month period and (b) to assess the effect of DHA supplementation on children’s sleep and cry patterns. Sixty toddlers were randomly allocated to four groups: 1. unfortified formula, 2. unfortified formula plus high DHA tuna oil, 3. fortified formula with dairy-based microencapsulated high DHA tuna oil powder, and 4. fortified formula with allergenic-free microencapsulated high DHA tuna oil powder. Bioavailability was assessed from both blood and faecal fatty acid levels. The results showed an enhanced bioavailability with significantly greater concentrations of blood DHA levels in formulas with microencapsulated powders. There were no significant effects of treatment on sleep and cry patterns. Application and delivery of microencapsulated DHA tuna oil powder in toddlers’ formula provided better bioavailability of the active DHA. Full article
(This article belongs to the Section Clinical Nutrition)
13 pages, 2926 KiB  
Article
Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset
by Michaela E. Murphy and Cara J. Westmark
Nutrients 2020, 12(1), 247; https://doi.org/10.3390/nu12010247 - 18 Jan 2020
Cited by 35 | Viewed by 13268
Abstract
The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, [...] Read more.
The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a population-based analysis of the Food Fortification Initiative dataset to determine the strength of the evidence regarding reports of decreased NTDs at the national level in response to mandatory folic acid fortification of cereal grains. We found a very weak correlation between NTD prevalence and the level of folic acid fortification, irrespective of the cereal grain fortified (wheat, maize or rice). Stratification of the data based on socioeconomic status (SES) indicated a strong linear relationship between reduced NTDs and better SES. We conclude that national fortification with folic acid is not associated with a significant decrease in the prevalence of NTDs at the population level. Full article
(This article belongs to the Special Issue Nutrition Status and Health)
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<p>Prevalence of NTDs as a function of folic acid fortification levels in wheat. The number of NTDs per 10,000 births was plotted (blue bars) versus country (<span class="html-italic">n</span> = 68). Folic acid fortification levels of wheat in ppm (orange bars) were superimposed on NTD prevalence. Linear regression analysis indicates a regression coefficient (a) of −1.07.</p>
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<p>Prevalence of NTDs as a function of folic acid fortification levels in maize. The number of NTDs per 10,000 births was plotted (blue bars) versus country (<span class="html-italic">n</span> = 17). Folic acid fortification levels of maize in ppm (orange bars) were superimposed on NTD prevalence. Linear regression analysis indicates a regression coefficient (a) of −1.15.</p>
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<p>Prevalence of NTDs as a function of folic acid fortification levels in rice. The number of NTDs per 10,000 births was plotted (blue bars) versus country (<span class="html-italic">n</span> = 17). Folic acid fortification levels of rice in ppm (orange bars) were superimposed on NTD prevalence. Linear regression analysis indicates a regression coefficient (a) of −6.57.</p>
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<p>Prevalence of NTDs as a function of folic acid fortification levels in rice. The number of NTDs per 10,000 births was plotted (blue bars) versus country (<span class="html-italic">n</span> = 17). Folic acid fortification levels of rice in ppm (orange bars) were superimposed on NTD prevalence. Linear regression analysis indicates a regression coefficient (a) of −6.57.</p>
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<p>Prevalence of NTDs in the absence of national folic acid fortification. The number of NTDs per 10,000 births was plotted (blue bars) versus country (<span class="html-italic">n</span> = 116).</p>
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19 pages, 3882 KiB  
Article
The Preparation of Ginsenoside Rg5, Its Antitumor Activity against Breast Cancer Cells and Its Targeting of PI3K
by Yannan Liu and Daidi Fan
Nutrients 2020, 12(1), 246; https://doi.org/10.3390/nu12010246 - 18 Jan 2020
Cited by 40 | Viewed by 5231
Abstract
Ginsenosides have been reported to possess various pharmacological effects, including anticancer effects. Nevertheless, there are few reports about the antitumor activity and mechanisms of ginsenoside Rg5 against breast cancer cells. In the present study, the major ginsenoside Rb1 was transformed into the rare [...] Read more.
Ginsenosides have been reported to possess various pharmacological effects, including anticancer effects. Nevertheless, there are few reports about the antitumor activity and mechanisms of ginsenoside Rg5 against breast cancer cells. In the present study, the major ginsenoside Rb1 was transformed into the rare ginsenoside Rg5 through enzymatic bioconversion and successive acid-assisted high temperature and pressure processing. Ginsenosides Rb1, Rg3, and Rg5 were investigated for their antitumor effects against five human cancer cell lines via the MTT assay. Among them, Rg5 exhibited the greatest cytotoxicity against breast cancer. Moreover, Rg5 remarkably suppressed breast cancer cell proliferation through mitochondria-mediated apoptosis and autophagic cell death. LC3B-GFP/Lysotracker and mRFP-EGFP-LC3B were utilized to show that Rg5 induced autophagosome-lysosome fusion. Western blot assays further illustrated that Rg5 decreased the phosphorylation levels of PI3K, Akt, mTOR, and Bad and suppressed the PI3K/Akt signaling pathway in breast cancer. Moreover, Rg5-induced apoptosis and autophagy could be dramatically strengthened by the PI3K/Akt inhibitor LY294002. Finally, a molecular docking study demonstrated that Rg5 could bind to the active pocket of PI3K. Collectively, our results revealed that Rg5 could be a potential therapeutic agent for breast cancer treatment. Full article
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Graphical abstract

Graphical abstract
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<p>The preparation of ginsenoside Rg5: (<b>A</b>) The two steps by which the ginsenoside Rb1 is converted into the ginsenoside Rg5 and (<b>B</b>) analytical chromatogram of the obtained ginsenoside Rg5. The bold “99.278%” represents the purity of the separated ginsenoside Rg5.</p>
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<p>The cytotoxic effects of Rb1, R-Rg3, S-Rg3, and Rg5 on various human cancer cell lines: MCF-7 cells (<b>A</b>), CACO-2 cells (<b>B</b>), SGC-7901 cells (<b>C</b>), NCI-H460 cells (<b>D</b>), and SMMC-7721 cells (<b>E</b>). * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control group.</p>
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<p>Rg5 suppresses cell viability and colony formation in human breast cancer cells. (<b>A</b>) The IC50 values of Rg5 after 48 h treatment were determined in NCI-H460, SMMC-7721, CACO-2, SGC-7901, and MCF-7 cells. (<b>B</b>) MCF-7 cells were incubated with Rg5 at different doses (0, 50, 100, and 150 μM) for 24 h and 48 h. Cell viability was detected via MTT assay. (<b>C</b>) Colony formation assay of MCF-7 cells with control or Rg5. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control group.</p>
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<p>Rg5 triggers apoptosis in human breast cancer cells. (<b>A</b>) AO/EB staining was performed to assess apoptosis-induced morphological variation via fluorescence microscopy. Scale bars = 100 μm. (<b>B−D</b>) MCF-7 cells were exposed to Rg5 at different concentrations for 24 h. (<b>B</b>) Cells were detected by flow cytometry after Annexin V-FITC/PI staining. The chart illustrates the proportion of apoptotic cells. (<b>C</b>) The relative mRNA expression levels of Bax and Bcl-2 were determined using real-time qRT-PCR. (<b>D</b>) The levels of apoptosis-related proteins were analyzed via Western blot assay. (<b>E, F</b>) MCF-7 cells were exposed to Rg5 (100 μM) in the presence of Z-VAD-FMK (100 μM). (<b>E</b>) The MTT assay was used to detect cell viability. (<b>F</b>) The expression levels of cleaved caspase-3 and cleaved PARP were determined via Western blot analysis. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control group. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 and <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 as compared with Rg5-treated cells.</p>
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<p>Rg5 induces apoptosis via mitochondria-mediated pathway. MCF-7 cells were exposed to Rg5 at various concentrations for 24 h. The mitochondrial membrane potential was analyzed with JC-10 staining using fluorescence microscopy (<b>A</b>) and flow cytometry (<b>B</b>). The histogram represents ratio of red/green fluorescence intensity. (<b>C</b>) The fluorescence images of MCF-7 cells after mitochondrial staining with MitoTracker Green. Scale bars = 20 μm. ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control.</p>
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<p>Rg5 triggers autophagy, which leads to cell death. (<b>A</b>) Autophagy was detected in MCF-7 cells after Rg5 exposure for 24 h via TEM. Arrows represent autophagosomes. Scale bars = 1 μm. (<b>B</b>,<b>C</b>) MCF-7 cells were exposed to Rg5 at different doses for 24 h. (<b>B</b>) The relative mRNA expression levels of LC3B and p62 were performed via real-time qRT-PCR. (<b>C</b>) Western blotting was performed to evaluate the expression of autophagy-related proteins. (<b>D</b>,<b>E</b>) MCF-7 cells were exposed to Rg5 (100 μM) in the presence of 3-MA (2 mM). (<b>D</b>) Cell viability was detected via MTT assay. (<b>E</b>) Expression levels of the LC3BII and p62 proteins were performed using Western blot analysis. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 and <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 as compared with Rg5-trated cells.</p>
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<p>Rg5 augments the fusion of autophagosomes and lysosomes in human breast cancer cells. (<b>A</b>) Upper panel represents the schematic diagram of tfLC3B. MCF-7 cells were transfected with tfLC3B-encoding plasmid and treated with 100 μM Rg5. Representative images are shown. (<b>B</b>) MCF-7 cells were treated with 100 μM Rg5 in combination with 2 mM 3-MA and subjected to immunofluorescence analyses for LC3B. Representative images are shown. (<b>C</b>) MCF-7 cells were transfected with GFP-LC3B-encoding plasmid, treated with 100 μM Rg5 in combination with 2 mM 3-MA, and stained with LysoTracker-Red. Representative fluorescence images are shown. Scale bars = 20 μm.</p>
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<p>Rg5 induces apoptosis and autophagy through inhibiting PI3K/Akt signaling pathways. (<b>A</b>) MCF-7 cells were treated with Rg5 at various concentrations for 24 h. The levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, Bad, and p-Bad were analyzed using Western blot analysis. (<b>B−D</b>) MCF-7 cells were exposed to Rg5 (100 μM) in the presence of LY294002 (20 μM) (<b>B</b>) The protein expression levels of members of the PI3K/Akt pathways were determined through Western blot analysis. (<b>C</b>) Cell viability was detected through MTT assay. (<b>D</b>) Western blot assay was performed to analyze the levels of cleaved caspase-3, cleaved PARP, LC3B II, and p62. (<b>E</b>) Predicted binding model of Rg5 with PI3K (docking score (S) is -10.8). Hydrogen bonds are shown as yellow dashed lines. Images are visualized by PyMoL. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 as compared with the control; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 and <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 as compared with Rg5-treated cells.</p>
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<p>Schematic representation of the hypothesized molecular mechanism underlying the anti-breast cancer activity of Rg5.</p>
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20 pages, 1837 KiB  
Article
Alpha-Lactalbumin Enriched Whey Protein Concentrate to Improve Gut, Immunity and Brain Development in Preterm Pigs
by Charlotte Holme Nielsen, Yan Hui, Duc Ninh Nguyen, Agnethe May Ahnfeldt, Douglas G. Burrin, Bolette Hartmann, Anne Birgitte Heckmann, Per Torp Sangild, Thomas Thymann and Stine Brandt Bering
Nutrients 2020, 12(1), 245; https://doi.org/10.3390/nu12010245 - 17 Jan 2020
Cited by 24 | Viewed by 6357
Abstract
Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that α-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm [...] Read more.
Human milk is rich in nutritional factors, such as alpha-lactalbumin (α-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that α-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm pigs were fed either dilute bovine milk (REF) or REF milk supplemented with WPC with normal (STANDARD-ALPHA) or high (HIGH-ALPHA) α-Lac. Clinical, gut, immune and cognitive endpoints (open field, T-maze) were assessed and tissues collected at Day 19. The growth of STANDARD-ALPHA and HIGH-ALPHA were higher than REF (31 vs. 19 g/kg/d). Most organ weights, gut, immunity and brain variables were similar between WPC groups. HIGH-ALPHA had a higher bone mineral content, colon microbial diversity and an abundance of specific bacteria and microbial metabolites, and tended to show a faster food transit time (p = 0.07). Relative to REF, WPC pigs showed higher relative organ weights, blood amino acids, blood neutrophil function, and microbial metabolites, but lower brush-border enzyme activities and plasma cortisol. Cognition outcomes did not differ among the groups. In conclusion, WPC supplementation of milk improved some growth, gut and immunity parameters in preterm pigs. However, increasing the α-Lac content beyond human milk levels had limited effects on the immature gut and developing brain. Full article
(This article belongs to the Section Clinical Nutrition)
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<p>Dual-energy X-ray absorptiometry (DEXA) scans of 19 day old preterm pigs fed a bovine milk diet supplemented with bovine whey protein concentrate either enriched with α-Lac (HIGH-ALPHA, <span class="html-italic">n</span> = 16) or with standard content of α-Lac (STANDARD-ALPHA, <span class="html-italic">n</span> = 17). Relative bone mineral content (BMC). Data are expressed as mean ± SD. Significant differences between groups are shown (** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Plasma concentrations of amino acids in preterm pigs fed a bovine milk diet supplemented with bovine whey protein concentrate either enriched with α-Lac (HIGH-ALPHA, <span class="html-italic">n</span> = 15) or with standard content of α-Lac (STANDARD-ALPHA, <span class="html-italic">n</span> = 15) measured in blood samples at Day 19. Data are expressed as mean ± SD. <span class="html-italic">p</span> = 0.09 indicates a tendency of a difference between groups.</p>
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<p>Structural gut endpoints measured in 19 day old preterm pigs fed a bovine milk diet supplemented with bovine whey protein concentrate, either enriched with α-Lac (HIGH-ALPHA, <span class="html-italic">n</span> = 15–18) or with standard content of α-Lac (STANDARD-ALPHA, <span class="html-italic">n</span> = 13–17). (<b>A</b>) Villus height and (<b>B</b>) Crypt depth. Data are expressed as mean ± SD. Significant differences between groups are shown (* <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>(<b>A</b>) Concentrations of microbial metabolites, including short chain fatty acids, in the colon of 19 day old preterm pigs fed a bovine milk diet supplemented with bovine whey protein concentrate, either enriched with α-Lac (HIGH-ALPHA, <span class="html-italic">n</span> = 16) or with standard content of α-Lac (STANDARD-ALPHA, <span class="html-italic">n</span> = 16). (<b>B</b>) Bacterial abundance in the tissue and lumen of distal small intestines based on FISH score. Microscopic visualization of distal small intestines from preterm pig diet groups with bacterial micro-colonies (HIGH-APLHA or STANDARD-ALPHA). Images representative of the standardized FISH-score interval of the means of both diet groups based on a fluorescent signal expressing the density of bacteria. (<b>C</b>) Score 2 (few bacteria on epithelium, locally); (<b>D</b>) score 3 (few bacteria on epithelium, globally) and (<b>E</b>) score 4 (medium abundance of bacteria on epithelium, locally). Data are expressed as mean ± SD. <span class="html-italic">p</span> = 0.06 indicates a tendency of difference between groups. Significant differences between groups are shown (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Gut microbiota determined by the 16s rRNA gene amplicon sequencing at Day 19 in preterm pigs fed a bovine milk diet supplemented with bovine whey protein concentrate either enriched with α-Lac (HIGH-ALPHA, <span class="html-italic">n</span> = 18) or with standard content of α-Lac (STANDARD-ALPHA, <span class="html-italic">n</span> = 17). Cumulative sum scaling (CSS) relative abundance of significantly differentially expressed bacterial genera in the colon, as determined by ANCOM.</p>
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Article
In Vivo Fat Quantification: Monitoring Effects of a 6-Week Non-Energy-Restricted Ketogenic Diet in Healthy Adults Using MRI, ADP and BIA
by Martin Buechert, Thomas Lange, Peter Deibert and Paul Urbain
Nutrients 2020, 12(1), 244; https://doi.org/10.3390/nu12010244 - 17 Jan 2020
Cited by 2 | Viewed by 7120
Abstract
The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess [...] Read more.
The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was >2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat. Full article
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<p>(<b>a</b>) Symbolic view of the definition of the abdominal magnetic resonance imaging (MRI) imaging volume (green box) between the top of the femoral heads (blue circle) and the liver (purple triangle) apex. (<b>b</b>) Corresponding MRI slices at four in (<b>a</b>) marked exemplary positions within the imaging volume. The dashed green lines within the MR-images show the segmentation borders of subcutaneous fat volume. Reconstructed images are based on the fat-water Dixon MR-images acquired with a spoiled gradient echo sequence (repetition time TR = 171 ms, four echo times TE = {1.11, 2.89, 4.67, 6.45} ms, a slice thickness of 6 mm, and an in-plane resolution of 2.3 mm).</p>
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<p>Line plots showing changes of individual subjects’ MRI data. Each plot on the left contains PRE values before diet and on the right contains POST values after six weeks. (<b>a</b>) Total tissue volume V<sub>t</sub> normalized to the total tissue volume PRE. (<b>b</b>) Total body weight normalized to the total body weight PRE (<b>c</b>) Subcutaneous volume V<sub>s</sub> normalized to V<sub>t</sub>. (<b>d</b>) Subcutaneous fat mass volume Vfm<sub>s</sub> normalized to V<sub>s.</sub> (<b>e</b>) Internal volume V<sub>i</sub> normalized to V<sub>t</sub>. (<b>f</b>) Internal fat mass volume Vfm<sub>i</sub> normalized to V<sub>i</sub>.</p>
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<p>Box plots fat mass (<b>right</b>) and fat-free mass (<b>left</b>) as percentage of the body weight measured by BIA (<b>top</b>), ADP (<b>center</b>) and MRI (<b>bottom</b>). X-axis labels before diet are ‘PRE’ and after six weeks are ‘POST’ values. MRI data restricted to the imaging volume, BIA and ADP values for the whole body. Extreme values are represented by circles (‘out’) and asterisks (‘far out’). Abbreviations: FFM = fat-free mass, FM = fat mass.</p>
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<p>Example water suppressed liver spectra with main peaks marked: a methylene (CH2) peak at 1.3 ppm, a methyl (CH3) peak at 0.9 ppm, α-olefinic and α-carboxyl peaks at 2.1 ppm, a diacyl peak at 2.8 ppm, and a choline peak at 3.2 ppm. The model fit (thin underlying grey line) of the single components fits the measured data (red dots) very well.</p>
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<p>Mean intrahepatic lipid (IHL) values for PRE and POST measurements. Scatter plot of individual values (<b>a</b>) and box plots of grouped values (<b>b</b>).</p>
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