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1.
Artificial Polymers made of α-amino Acids - Poly(Amino Acid)s, Pseudo-Poly(Amino Acid)s, Poly(Depsipeptide)s, and Pseudo-Proteins.
Zavradashvili, N, Puiggali, J, Katsarava, R
Current pharmaceutical design. 2020;(5):566-593
Abstract
Degradable polymers (DPs) - "green materials" of the future, have an innumerable use in biomedicine, particularly in the fields of tissue engineering and drug delivery. Among these kind of materials naturally occurring polymers - proteins which constituted one of the most important "bricks of life" - α-amino acids (AAs) are highly suitable. A wide biomedical applicability of proteins is due to special properties such as a high affinity with tissues and releasing AAs upon biodegradation that means a nutritive potential for cells. Along with these positive characteristics proteins as biomedical materials they have some shortcomings, such as batch-to-batch variation, risk of disease transmission, and immune rejection. The last limitation is connected with the molecular architecture of proteins. Furthermore, the content of only peptide bonds in protein molecules significantly restricts their material properties. Artificial polymers with the composition of AAs are by far more promising as degradable biomaterials since they are free from the limitations of proteins retaining at the same time their positive features - a high tissue compatibility and nutritive potential. The present review deals with a brief description of different families of AA-based artificial polymers, such as poly(amino acid)s, pseudo-poly(amino acid)s, polydepsipeptides, and pseudo-proteins - relatively new and broad family of artificial AA-based DPs. Most of these polymers have a different macromolecular architecture than proteins and contain various types of chemical links along with NH-CO bonds that substantially expands properties of materials destined for sophisticated biomedical applications.
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2.
The significant role of amino acids during pregnancy: nutritional support.
Manta-Vogli, PD, Schulpis, KH, Dotsikas, Y, Loukas, YL
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(2):334-340
Abstract
Background: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces, and interconverts amino acids (AAs).Findings: Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally, there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (e.g. glutamine, glutamate, and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function.Conclusions: Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan-vegetarian groups, and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.
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3.
Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
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4.
d-amino Acids in Health and Disease: A Focus on Cancer.
Bastings, JJAJ, van Eijk, HM, Olde Damink, SW, Rensen, SS
Nutrients. 2019;(9)
Abstract
d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.
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5.
The use of amino acid-based nutritional feeds is effective in the dietary management of pediatric eosinophilic oesophagitis.
Atwal, K, Hubbard, GP, Venter, C, Stratton, RJ
Immunity, inflammation and disease. 2019;(4):292-303
Abstract
INTRODUCTION Eosinophilic oesophagitis (EoE) is an immune-mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. METHODS Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. RESULTS Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%-100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%-81% and 40%-69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long-term impacts of each diet were not thoroughly explored. CONCLUSIONS The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long-term management.
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6.
A Pilot Study of Amino Acids in Unresectable Non-Small-Cell Lung Cancer Patients During Chemotherapy: A Randomized Serial N-of-1 Trials Design.
Liu, L, Zhang, Y, Wei, J, Chen, Z, Yu, J
Nutrition and cancer. 2019;(3):399-408
Abstract
The aim of this study was to evaluate the effect of amino acids (AAs) on immune function and inflammation level in patients with NSCLC receiving chemotherapy. We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing AAs with isocaloric glucose in unresectable NSCLC patients and combined the individual results using Bayesian statistical modeling. 25 patients completed two cycles of chemotherapy. The baseline total blood albumin (ALB) level in all patients was 28 ± 3.3 g/l, and the mean total ALB level in patients receiving AAs supplementation and isocaloric glucose was 29.2 ± 2.2 and 28.1 ± 3.7 g/l, respectively (P = 0.028). Patients' baseline C-reactive protein (CRP) level was 4 ± 1.2 mg/l, the mean total CRP level in patients receiving AAs supplementation and isocaloric glucose was 11 ± 2.8 and 13 ± 3.2 mg/l, respectively (P = 0.028). The baseline total blood CD4+ T cells level was 36 ± 7.8%. The percentage of CD4+ T cells in patients receiving AAs supplementation and isocaloric glucose was 42 ± 6.4 and 33.7 ± 17.3, respectively (P = 0.034). Our preliminary results indicated that AAs improve immune status and suppress inflammation in unresectable NSCLC patients receiving chemotherapy.
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7.
Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children.
Spanaki, AM, Tavladaki, T, Dimitriou, H, Kozlov, AV, Duvigneau, JC, Meleti, E, Weidinger, A, Papakonstantinou, E, Briassoulis, G
JPEN. Journal of parenteral and enteral nutrition. 2018;(6):1061-1074
Abstract
BACKGROUND Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (p<0.05); TBARS and VO2 were independently associated with organ failure (p<0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (p<0.05). CONCLUSIONS A pattern of early longitudinal induction of metabolic-hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.
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8.
Identification of Strategic Residues at the Interface of Antigen-Antibody Interactions by In Silico Mutagenesis.
Xin, L, Yu, H, Hong, Q, Bi, X, Zhang, X, Zhang, Z, Kong, Z, Zheng, Q, Gu, Y, Zhao, Q, et al
Interdisciplinary sciences, computational life sciences. 2018;(2):438-448
Abstract
Structural information pertaining to antigen-antibody interactions is fundamental in immunology, and benefits structure-based vaccine design. Modeling of antigen-antibody immune complexes from co-crystal structures or molecular docking simulations provides an extensive profile of the epitope at the interface; however, the key amino acids involved in the interaction must be further clarified, often through the use of experimental mutagenesis and subsequent binding assays. Here, we describe an in silico mutagenesis method to identify key sites at antigen-antibody interfaces, using significant increase in pH-dependency energy among saturated point mutations. Through a comprehensive analysis of the crystal structures of three antigen-antibody immune complexes, we show that a cutoff value of 1 kcal/mol of increased interaction energy provides good congruency with the experimental non-binding mutations conducted in vitro. This in silico mutagenesis strategy, in association with energy calculations, may provide an efficient tool for antibody-antigen interface analyses, epitope optimization, and/or conformation prediction in structure-based vaccine design.
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9.
Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial.
Ripken, D, van Avesaat, M, Troost, FJ, Masclee, AA, Witkamp, RF, Hendriks, HF
Clinical nutrition (Edinburgh, Scotland). 2017;(1):143-149
Abstract
BACKGROUND Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. OBJECTIVE To investigate the effects of intraileal infusion of native casein on plasma amino acid appearance, immune activation and gastrointestinal (GI) symptoms. DESIGN A randomized single-blind cross over study was performed in 13 healthy subjects (6 male; mean age 26 ± 2.9 years; mean body mass index 22.8 ± 0.4 kg/m-2), who were intubated with a naso-ileal feeding catheter. Thirty minutes after intake of a standardized breakfast, participants received an ileal infusion, containing either control (C) consisting of saline, a low-dose (17.2 kcal) casein (LP) or a high-dose (51.7 kcal) of casein (HP) over a period of 90 min. Blood samples were collected for analysis of amino acids (AAs), C-reactive protein (CRP), pro-inflammatory cytokines and oxylipins at regular intervals. Furthermore, GI symptom questionnaires were collected before, during and after ileal infusion. RESULTS None of the subjects reported any GI symptoms before, during or after ileal infusion of C, LP and HP. Plasma concentrations of all AAs analyzed were significantly increased after infusion of HP as compared to C (p < 0.001), and most AAs were increased after infusion of LP (p < 0.001). In total, 12.49 ± 1.73 and 3.18 ± 0.87 g AAs were found in plasma after intraileal infusion of HP and LP, corresponding to 93 ± 13% (HP) and 72 ± 20% (LP) of AAs infused as casein, respectively. Ileal casein infusion did not affect plasma concentrations of CRP, IL-6, IL-8, IL-1β and TNF-α. Infusion of HP resulted in a decreased concentration of 11,12-dihydroxyeicosatrienoic acid whereas none of the other oxylipins analyzed were affected. CONCLUSIONS A single intraileal infusion of native casein results in a concentration and time dependent increase of AAs in plasma, suggesting an effective digestion and absorption of AAs present in casein. Also, ileal infusion did not result in immune activation nor in GI symptoms. CLINICALTRIALS.GOV: NCT01509469.