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Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor, or quality needed for definitive statements of efficacy regarding clinical end points. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence (AI), and machine learning-all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this article are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.
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Suplementos Dietéticos , Humanos , Inteligencia Artificial , Suplementos Dietéticos/historia , Suplementos Dietéticos/normas , Nutrigenómica , Estados UnidosRESUMEN
Introduction: Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED. Methods: Participants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer's test) and ocular symptoms (Ocular Surface Disease Index [OSDI]). Results: The study met its primary endpoints: the LCD group demonstrated significantly better Schirmer's test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p<0.001 for both). Scores for total OSDI, and symptoms and vision domains, significantly improved by Day 14 for LCD versus placebo, (p<0.05 for all) and were maintained to Day 56 (p<0.001). In addition, the LCD group demonstrated significantly improved tear film break-up time (TBUT) and tear film osmolarity, versus placebo, by Day 56 (p<0.001), along with significant improvements in corneal and conjunctival staining (p<0.001 for both), and inflammation (matrix metalloproteinase-9; p<0.001 for each eye). Total Standard Patient Evaluation of Eye Dryness (SPEED) score, and scores for the frequency and severity domains, were significantly improved by Day 14 for LCD versus placebo (p<0.05 for all) and maintained to Day 56 (p<0.001). There was no difference between groups for artificial tear usage. The supplement was well-tolerated. Discussion: Once-daily LCD supplementation significantly improved tear production, stability and quality, reduced ocular surface damage and inflammation, and improved participants' symptoms. LCD supplementation could offer a useful adjunct to artificial tears for patients with DED (NCT05481450).
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INTRODUCTION: Lutein (L) and zeaxanthin (Z) are carotenoids that are found in the macula of the human eye and are known to improve visual functions. However, poor bioavailability of supplemental L and Z poses a challenge to achieving significant benefits after consumption. We developed a novel patented formulation of L and Z (Ocusorb®) and demonstrated the improved bioavailability in a pharmacokinetic clinical study. METHODS: Ninety adult human volunteers were recruited in this randomized, double-blind, parallel, comparative bioavailability study. Volunteers were randomly assigned to receive single dose of 10 mg lutein and 2 mg zeaxanthin from test (LZO) or reference (LZC) formulations after breakfast. Blood samples were collected pre-dose at - 48, - 24, and 0 h and at 2, 4, 6, 8, 10, 12, 16, 20, 24, 48, and 72 h post-dose. Serum concentrations of L and Z were quantified by using a validated HPLC method. The LZO and LZC formulations were compared for L and Z on the basis of Cmax, AUC0-72, and AUC0-t. RESULTS: All 90 subjects completed the study. The LZO group demonstrated significantly higher levels of L and Z in serum at several time points as compared to LZC group. The LZO group showed significantly higher bioavailability for lutein (2.5 times higher Cmax, 2.9 times higher AUC0-72, and 3.2 times higher AUC0-t) and zeaxanthin (1.8 times higher Cmax, 2.2 times higher AUC0-72, and AUC0-t) as compared to the LZC group. No safety issues were reported. CONCLUSION: The study results show superior bioavailability of lutein and zeaxanthin from our novel LZO formulation as compared to LZC. The enhanced bioavailability from the LZO formulation can be advantageous for individuals looking to quickly improve their L and Z status and enhance their vision performance. TRIAL REGISTRATION: http://ctri.nic.in/ . Identifier: CTRI/2019/11/022082.
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The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to 'prevent deficiency' with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual's nutritional status, and serve to provide personalized nutrition guidance.
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Promoción de la Salud , Política Nutricional/legislación & jurisprudencia , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Promoción de la Salud/legislación & jurisprudencia , Promoción de la Salud/normas , Humanos , Luteína , Estado Nutricional , Ingesta Diaria Recomendada , Estados Unidos , Vitamina KRESUMEN
Obesity is a significant public health concern, and finding safe and effective means for combating this condition is needed. This study investigates the safety and efficacy of supplementation of a blend of capsaicinoids on weight gain, fat mass, and blood chemistry in a high-fat diet (HFD) model of obesity in mice and on adipocyte differentiation and gene expression in 3T3-L1 preadipocytes. High-fat diet (HFD)-fed mice were treated with a proprietary capsaicinoid concentrate (Capsimax®; OmniActive Health Technologies Ltd., India) and compared to orlistat (ORL) and normal chow-fed mice (NC). Mice fed a high-fat diet showed significantly lower weight gain upon Capsimax® (CAP) administration than their HFD counterparts and similar to that observed with ORL animals. In addition, CAP decreased the high-fat diet-induced increases in adipose tissue and epididymal fat pad mass and hypertrophy after 52 days of treatment. Both the CAP and ORL groups had increased plasma concentrations of leptin. CAP extracts decreased triacylglycerol content in 3T3-L1 preadipocytes and decreased markers of adipogenesis including peroxisome proliferator-activated receptor (PPAR-É£) and fatty acid-binding protein 4 (FABP4). Expression of genes involved in lipogenesis such as stearoyl-CoA desaturase (SCD) and fatty acid synthase (FSN) was decreased by CAP in a dose-dependent manner. Thermogenic genes and markers of brown adipose tissue including uncoupling protein 1 (UCP1) and PR domain-containing 16 (Prdm16) were induced by CAP in the preadipocyte cells. These in vivo and in vitro data support that this proprietary capsaicinoid concentrate reduces weight gain and adiposity at least in part through decreasing lipogenesis and increasing thermogenesis.
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Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. ß-Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1ß, IL-6, and NF-κB), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.
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beta-Criptoxantina/farmacología , Luz , Estrés Oxidativo/efectos de la radiación , Retina/patología , Retina/efectos de la radiación , Animales , Relación Dosis-Respuesta a Droga , Proteínas del Ojo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdehído/metabolismo , Modelos Biológicos , FN-kappa B/metabolismo , Ratas Wistar , Retina/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. In this study, the protective effect of different doses (100 or 200 mg/kg) of a novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated using a rat model with benzalkonium chloride (BAC)-induced dry eye syndrome. The formulation was administered orally to rats for 4 weeks. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation in rats fed with the LCD at dose 200 mg/kg performing better than 100 mg/kg. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action.
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OBJECTIVE: Understanding nutrient intakes among women of childbearing age within the USA is important given the accumulating evidence that maternal body weight gain and nutrient intakes prior to pregnancy may influence the health and well-being of the offspring. The objective of the present study was to evaluate nutritional status in women of childbearing age and to ascertain the influence of ethnicity and income on nutrient intakes. DESIGN: Nutritional status was assessed using data on nutrient intakes through foods and supplements from the National Health and Nutrition Examination Survey. Biomarker data from the Centers for Disease Control and Prevention were used to assess nutritional status for selected nutrients. Poverty-income ratio was used to assess family income. SUBJECTS: White (n 1560), African-American (n 889) and Mexican-American (n 761) women aged 19-30 and 31-50 years were included. SETTING: A nationally representative sample of non-pregnant women of childbearing age resident in the USA. RESULTS: African-American women had the lowest intakes of fibre, folate, riboflavin, P, K, Ca and Mg. Women (31-50 years) with a poverty-income ratio of ≤ 1.85 had significantly lower intakes of almost all nutrients analysed. Irrespective of ethnicity and income, a significant percentage of women were not consuming the estimated recommended amounts (Estimated Average Requirement) of several key nutrients: vitamin A (~80%), vitamin D (~78%) and fibre (~92%). Nutrient biomarker data were generally reflective of nutrient intake patterns among the different ethnic groups. CONCLUSIONS: Women of childbearing age in the USA are not meeting nutrient intake guidelines, with differences between ethnic groups and socio-economic strata. These factors should be considered when establishing nutrition science advocacy and policy.
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Biomarcadores , Ingestión de Energía , Etnicidad , Evaluación Nutricional , Estado Nutricional , Adolescente , Adulto , Femenino , Humanos , Renta , Encuestas Nutricionales , Necesidades Nutricionales , Pobreza , Estados UnidosRESUMEN
Lactoferrin is the second most abundant whey protein in human milk and is known for its functional benefits, particularly antimicrobial activities. We report a comprehensive evaluation of the published literature on quantitative changes in lactoferrin in term and preterm human milk through the course of lactation. We also considered methods used to quantify lactoferrin. We critically evaluated 94 articles on human milk with 52 meeting study inclusion criteria (2724 women). A descriptive analysis of the data was performed. Lactoferrin concentration was highest during early lactation and rapidly declined to remain relatively unchanged from 1 month to 2 years of lactation. The unweighted mean of mean (±SEM) concentrations of lactoferrin in early milk (<28 days lactation) was 4.91 ± 0.31 g/L (range of means 0.34-17.94 g/L; median 4.03). For mature milk, the mean of means was 2.10 ± 0.87 g/L (range of means 0.44-4.4 g/L; median 1.91). The majority of data were derived from Europe with fewer studies from Africa and South America. There was a paucity of data on preterm milk. This comprehensive dataset explains in detail the longitudinal changes of lactoferrin concentrations in human milk throughout the world and briefly describes factors that may influence these concentrations.
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Lactoferrina/análisis , Leche Humana/química , África , Europa (Continente) , Femenino , Humanos , Lactancia , Proteínas de la Leche/química , América del Sur , Proteína de Suero de LecheRESUMEN
Amino acid profile is a key aspect of human milk (HM) protein quality. We report a systematic review of total amino acid (TAA) and free amino acid (FAA) profiles, in term and preterm HM derived from 13 and 19 countries, respectively. Of the 83 studies that were critically reviewed, 26 studies with 3774 subjects were summarized for TAA profiles, while 22 studies with 4747 subjects were reviewed for FAA. Effects of gestational age, lactation stage, and geographical region were analyzed by Analysis of Variance. Data on total nitrogen (TN) and TAA composition revealed general inter-study consistency, whereas FAA concentrations varied among studies. TN and all TAA declined in the first two months of lactation and then remained relatively unchanged. In contrast, the FAA glutamic acid and glutamine increased, peaked around three to six months, and then declined. Some significant differences were observed for TAA and FAA, based on gestational age and region. Most regional TAA and FAA data were derived from Asia and Europe, while information from Africa was scant. This systematic review represents a useful evaluation of the amino acid composition of human milk, which is valuable for the assessment of protein quality of breast milk substitutes.
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Aminoácidos/química , Lactancia , Proteínas de la Leche/química , Leche Humana/química , Femenino , Edad Gestacional , HumanosRESUMEN
OBJECTIVES: The aim of the study was to determine the effect of polydextrose (PDX) and galactooligosaccharide (GOS) on bacterial translocation (BT) in neonatal piglets. MATERIALS AND METHODS: Piglets (n = 36) were randomized 12 hours after birth to receive total enteral nutrition (TEN) as formula; TEN + GOS (4 g/L), TEN + PDX (4 g/L), or TEN + GOS + PDX (2 g/L each) for 7 days or were supported by total parenteral nutrition (TPN) as a positive control for BT (n = 8). Blood, spleen, liver, and mesenteric lymph node (MLN) samples were cultured for aerobic and anaerobic bacteria. Colon microbiota 16S rDNA was measured by polymerase chain reaction. Myeloperoxidase activity and tumor necrosis factor-α expression were measured in ileum and ascending colon. RESULTS: Among the enterally fed groups, no difference was seen in the Lactobacillus and Bacteroides 16S rDNA copies per gram of colonic contents, yet total bacterial levels were lower (P < 0.05) in the TEN + GOS group compared with TEN alone. Bacteria were detected in the blood, liver spleen, and MLN of TPN piglets. In contrast, bacterial counts were predominantly detected in the MLN of TEN piglets, at much lower levels than in TPN, and levels were not affected by GOS and PDX addition. TPN piglets had elevated (P < 0.05) ileal myeloperoxidase activity and a trend in elevated ascending colon tumor necrosis factor-α expression (P = 0.1). CONCLUSIONS: PDX and GOS added to formula do not induce BT in healthy piglets. Low levels of bacteria in MLN of healthy neonatal piglets may reflect mucosal sampling rather than pathological BT.
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Traslocación Bacteriana/efectos de los fármacos , Bacteroides fragilis/fisiología , Enterobacteriaceae/fisiología , Aditivos Alimentarios/farmacología , Glucanos/farmacología , Fórmulas Infantiles/química , Lactobacillus/fisiología , Trisacáridos/farmacología , Animales , Animales Recién Nacidos , Colon/patología , Nutrición Enteral , Íleon/patología , Distribución Aleatoria , PorcinosRESUMEN
We have developed a novel molecular methodology that utilizes stool samples containing intact sloughed epithelial cells to quantify intestinal gene expression profiles in the developing human neonate. Since nutrition exerts a major role in regulating neonatal intestinal development and function, our goal was to identify gene sets (combinations) that are differentially regulated in response to infant feeding. For this purpose, fecal mRNA was isolated from exclusively breast-fed (n = 12) and formula-fed (n = 10) infants at 3 mo of age. Linear discriminant analysis was successfully used to identify the single genes and the two- to three-gene combinations that best distinguish the feeding groups. In addition, putative "master" regulatory genes were identified using coefficient of determination analysis. These results support our premise that mRNA isolated from stool has value in terms of characterizing the epigenetic mechanisms underlying the developmentally regulated transcriptional activation/repression of genes known to modulate gastrointestinal function. As larger data sets become available, this methodology can be extended to validation and, ultimately, identification of the main nutritional components that modulate intestinal maturation and function.
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Células Epiteliales/metabolismo , Heces/química , Tracto Gastrointestinal/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales del Lactante , Adulto , Lactancia Materna , Femenino , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Humanos , Fórmulas Infantiles , Recién Nacido , Masculino , Análisis por Micromatrices , Embarazo , ARN Mensajero/metabolismoRESUMEN
As part of the workshop entitled "Early Risk Determinants and Later Health Outcomes: Implications for Research Prioritization and the Food Supply" (8-9 July 2008, Washington, DC), which was cosponsored by the International Life Sciences Institute of North America and the International Life Sciences Institute Research Foundation, representatives of the food industry discussed the practical application of nutrition science. Nutrition plays a key role in guiding health outcomes throughout the life cycle. In particular, the prenatal, postnatal, and early childhood periods are extremely sensitive to the presence of appropriate nutrition. A growing body of evidence shows that early nutrition may program the unborn and the infant's key physiologic systems, including the endocrine, cardiovascular, and central nervous systems, to influence later life outcomes. While scientists in academia continue to explore the multifactorial nature of early risk determinants and later life outcomes at a mechanistic and basic science level, it is important to understand the potential of the infant and child food industries to address questions such as what factors have been noted to drive research in these sectors of the food industry. How can scientists in these industries work alongside the scientists in academia and in government to set priorities, make decisions around these health issues, and translate academic insights into innovative nutritional solutions for the benefit of public health? Given the commitment of the infant and child food industries to deliver scientifically supported early life nutrition, it is easy to understand why this industry would work in partnership with both the scientists in academia and the government to identify a means of addressing the fundamental questions of this workshop.
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Fenómenos Fisiológicos Nutricionales Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante , Investigación/tendencias , Lactancia Materna , Niño , Alimentos/normas , Estado de Salud , Humanos , Lactante , Alimentos Infantiles/normas , Leche HumanaRESUMEN
Supplementation of infant formulas with prebiotic ingredients continues the effort to mimic functional properties of human milk. In this double-blind, controlled, 28-day study, healthy term infants received control formula (control group; n = 25) or control formula supplemented with polydextrose (PDX) and galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n = 27) or with PDX, GOS, and lactulose (LOS) (either 4 g/liter [PGL4 group; n = 27] or 8 g/liter [PGL8 group; n = 25]). A parallel breast-fed group (BF group) (n = 30) was included. Stool characteristics, formula tolerance, and adverse events were monitored. Fecal bacterial subpopulations were evaluated by culture-based selective enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis. The daily stool consistency was significantly softer or looser in the BF group than in all of the groups that received formula. The formulas were well tolerated, and the incidences of adverse events did not differ among feeding groups. Few significant changes in bacterial subpopulations were observed at any time point. The bacterial communities were stable; individual profiles tended to cluster by subject rather than by group. Post hoc analysis, however, demonstrated that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8 groups that first received formula at a younger age were less stable than the profiles for subjects in the same groups that received formula at an older age, but there was no difference for the control group. These data indicate that formulas containing PDX, GOS, and LOS blends are more likely to influence gut microbes when administration is begun in early infancy and justify further investigation of the age-related effects of these blends on fecal microbiota.
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Bacterias/clasificación , Recuento de Colonia Microbiana , Suplementos Dietéticos/efectos adversos , Heces/microbiología , Tracto Gastrointestinal/fisiología , Fórmulas Infantiles/administración & dosificación , Fenómenos Fisiológicos Nutricionales del Lactante , Método Doble Ciego , Electroforesis/métodos , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. OBJECTIVE: The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. DESIGN: Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. RESULTS: The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. CONCLUSION: Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.
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Ácido Araquidónico/farmacología , Ácidos Docosahexaenoicos/farmacología , Infecciones por Orthomyxoviridae/inmunología , Linfocitos T/inmunología , Administración Oral , Animales , Animales Recién Nacidos , Ácido Araquidónico/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Modelos Animales , Porcinos , Linfocitos T/efectos de los fármacosRESUMEN
Estrogens regulate multiple activities in breast cancer cells, including proliferation. Whereas these hormones are most commonly known to regulate gene transcription through direct interaction with estrogen receptors (ERs) and with specific DNA sequences of target genes, recent studies show that ER also activates a number of rapid signaling events that are initiated at the cell membrane. To study the membrane-initiated effects of estrogen and separate them from the activities initiated by the nuclear localized ER in human breast cancer cells, we generated MDA-MB-231 breast cancer cell lines that have stably integrated either the wild-type nuclear form of ER (WT-ER) or a modified, membrane-targeted ER (MT-ER) that lacks a nuclear localization sequence and is dually acylated with a myristoylation sequence at the N terminus and a palmitoylation sequence at the C terminus. We demonstrate that MT-ER is membrane localized in the absence of estradiol (E2), showing punctate membrane and cytoplasmic speckles after E2 exposure. In contrast to WT-ER, MT-ER was not down-regulated by E2 or by antiestrogen ICI 182,780 exposure, and MT-ER failed to regulate endogenous E2-responsive genes highly up-regulated by WT-ER. Cells expressing MT-ER showed a greater serum response element-mediated transcriptional response that was partially inhibited by antiestrogen ICI 182,780. The MT-ER and WT-ER differentially altered ERK1/2 and Akt activities and the proliferation of breast cancer cells in response to E2. Hence, this study reveals distinct actions of the MT-ER vs. the WT-ER in effecting estrogen actions in breast cancer cells.