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      A Review of Bioactive Factors in Human Breastmilk: A Focus on Prematurity

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          Abstract

          Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.

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          Proinflammatory cytokines.

          To review the concept of proinflammatory cytokines. Review of published literature. Academic (university hospital). Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). Attention also has focused on blocking cytokines, which are harmful to the host, particularly during overwhelming infection. Interleukin (IL)-1 and tumor necrosis factor (TNF) are proinflammatory cytokines, and when they are administered to humans, they produce fever, inflammation, tissue destruction, and, in some cases, shock and death. Reducing the biological activities of IL-1 and TNF is accomplished by several different, but highly specific, strategies, which involve neutralizing antibodies, soluble receptors, receptor antagonist, and inhibitors of proteases that convert inactive precursors to active, mature molecules. Blocking IL-1 or TNF has been highly successful in patients with rheumatoid arthritis, inflammatory bowel disease, or graft-vs-host disease but distinctly has not been successful in humans with sepsis. Agents such as TNF-neutralizing antibodies, soluble TNF receptors, and IL-1 receptor antagonist have been infused into > 10,000 patients in double-blind, placebo-controlled trials. Although there has been a highly consistent small increase (2 to 3%) in 28-day survival rates with anticytokine therapy, the effect has not been statistically significant. Anticytokine therapy should be able to "rescue" the patient whose condition continues to deteriorate in the face of considerable support efforts. Unfortunately, it remains difficult to identify those patients who would benefit from anticytokine therapy for septic shock.
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            Roles of enzymatic and nonenzymatic antioxidants in plants during abiotic stress.

            Reactive oxygen species (ROS) are produced in plants as byproducts during many metabolic reactions, such as photosynthesis and respiration. Oxidative stress occurs when there is a serious imbalance between the production of ROS and antioxidant defense. Generation of ROS causes rapid cell damage by triggering a chain reaction. Cells have evolved an elaborate system of enzymatic and nonenzymatic antioxidants which help to scavenge these indigenously generated ROS. Various enzymes involved in ROS-scavenging have been manipulated, over expressed or downregulated to add to the present knowledge and understanding the role of the antioxidant systems. The present article reviews the manipulation of enzymatic and nonenzymatic antioxidants in plants to enhance the environmental stress tolerance and also throws light on ROS and redox signaling, calcium signaling, and ABA signaling.
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              Glutathione dysregulation and the etiology and progression of human diseases.

              Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 June 2019
                June 2019
                : 11
                : 6
                : 1307
                Affiliations
                [1 ]Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, Spain; andrea.gila@ 123456estudiante.uam.es (A.G.-D.); silvia.arribas@ 123456uam.es (S.M.A.); alba.algara@ 123456estudiante.uam.es (A.A.); angel.lopezdepablo@ 123456uam.es (Á.L.L.d.P.)
                [2 ]Department of Agricultural Chemistry and Food Science, Universidad Autónoma de Madrid, Institute of Food Science Research, CIAL (UAM-CSIC), 28049 Madrid, Spain; maria.martin@ 123456uam.es
                [3 ]Neonatology Service, La Paz Hospital-Universidad Autónoma de Madrid, 28046 Madrid, Spain; miguel.saenz@ 123456salud.madrid.org
                [4 ]Carlos III Health Institute, Maternal and Child Health and Development Research Network, 28029 Madrid, Spain
                Author notes
                [* ]Correspondence: david.ramiro@ 123456uam.es ; Tel.: +34-914-975-416
                Author information
                https://orcid.org/0000-0001-7442-1586
                Article
                nutrients-11-01307
                10.3390/nu11061307
                6628333
                31185620
                a47ea8b7-fb0d-42ad-b015-0bfff75beb6f
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 April 2019
                : 04 June 2019
                Categories
                Review

                Nutrition & Dietetics
                adipokines,antioxidants,breastfeeding,cytokines,growth factors
                Nutrition & Dietetics
                adipokines, antioxidants, breastfeeding, cytokines, growth factors

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