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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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Site-selective covalent reactions on proteinogenic amino acids.
So, WH, Zhang, Y, Kang, W, Wong, CTT, Sun, H, Xia, J
Current opinion in biotechnology. 2017;:220-227
Abstract
To achieve precise control of the signaling events or to achieve unmistakable synthesis of biomolecules, nature has evolved organic reactions involving proteinogenic amino acids with unparalleled site selectivity. For example, dedicated enzymes accurately dictate the site of post-translational modifications in signaling proteins, and ribosomes precisely link the C-terminal carboxylic acid of one unprotected amino acid with the N-terminal amino group of the other amino acid through spatially confined proximity. For many years, chemists have been striving to achieve site selectivity on biomolecules by mimicking nature. Driven by the development of chemoselective protein conjugation reactions, enzymology and protein-protein interactions, the past decade has witnessed a boom in site-selective protein conjugation reactions. (In this review, a site-selective protein conjugation reaction is defined as an organic reaction that targets a single amino acid instead of a kind of amino acids in a protein or a proteome under physiological conditions, for example, a single cysteine residue among all of the cysteines.) In this review, we summarize the recent advancements of bioconjugation reactions that demonstrate this feature of precise site selectivity, focusing on the reactions of the proteinogenic amino acids (excluding those at non-coded or non-proteinogenic amino acids that are introduced to proteins through genetic manipulations).
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3.
Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein.
Delic, V, Griffin, JWD, Zivkovic, S, Zhang, Y, Phan, TA, Gong, H, Chaput, D, Reynes, C, Dinh, VB, Cruz, J, et al
Neuromolecular medicine. 2017;(2-3):322-344
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decreased by alpha-synuclein overexpression, but ATP levels did not decrease and ROS levels did not increase. Treatment with ferrous sulfate, a ROS generator, resulted in decreased oxygen consumption in both control and alpha-synuclein overexpressing cells. However, this treatment only decreased ATP levels and increased ROS production in the cells overexpressing alpha-synuclein. Similarly, paraquat, another ROS generator, decreased ATP levels in the alpha-synuclein overexpressing cells, but not in the control cells, further demonstrating how alpha-synuclein sensitized the cells to oxidative insult. Proteomic analysis yielded molecular insights into the cellular adaptations to alpha-synuclein overexpression, such as the increased abundance of many mitochondrial proteins. Many amino acids and citric acid cycle intermediates and their ester forms were individually supplemented to the cells with L-serine, L-proline, L-aspartate, or L-glutamine decreasing ROS production in oxidatively stressed alpha-synuclein overexpressing cells, while diethyl oxaloacetate or L-valine supplementation increased ATP levels. These results suggest that dietary supplementation with individual metabolites could yield bioenergetic improvements in PD patients to delay loss of dopaminergic neurons.
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Co-adaption of tRNA gene copy number and amino acid usage influences translation rates in three life domains.
Du, MZ, Wei, W, Qin, L, Liu, S, Zhang, AY, Zhang, Y, Zhou, H, Guo, FB
DNA research : an international journal for rapid publication of reports on genes and genomes. 2017;(6):623-633
Abstract
Although more and more entangled participants of translation process were realized, how they cooperate and co-determine the final translation efficiency still lacks details. Here, we reasoned that the basic translation components, tRNAs and amino acids should be consistent to maximize the efficiency and minimize the cost. We firstly revealed that 310 out of 410 investigated genomes of three domains had significant co-adaptions between the tRNA gene copy numbers and amino acid compositions, indicating that maximum efficiency constitutes ubiquitous selection pressure on protein translation. Furthermore, fast-growing and larger bacteria are found to have significantly better co-adaption and confirmed the effect of this pressure. Within organism, highly expressed proteins and those connected to acute responses have higher co-adaption intensity. Thus, the better co-adaption probably speeds up the growing of cells through accelerating the translation of special proteins. Experimentally, manipulating the tRNA gene copy number to optimize co-adaption between enhanced green fluorescent protein (EGFP) and tRNA gene set of Escherichia coli indeed lifted the translation rate (speed). Finally, as a newly confirmed translation rate regulating mechanism, the co-adaption reflecting translation rate not only deepens our understanding on translation process but also provides an easy and practicable method to improve protein translation rates and productivity.
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5.
Examination of Chinese habitual dietary protein requirements of Chinese young female adults by indicator amino acid method.
Tian, Y, Liu, J, Zhang, Y, Piao, J, Gou, L, Tian, Y, Li, M, Ji, Y, Yang, X
Asia Pacific journal of clinical nutrition. 2011;(3):390-6
Abstract
OBJECTIVE To determine protein requirement of Chinese young female adults on habitual Chinese diet through indicator amino acid oxidation (IAAO) technique. DESIGN Twenty women with a mean (SD) age of 21.6 (0.9) years were healthy based on questionnaire, physical examinations and screening tests. There were three consecutive periods of 7 days each with six different intakes of protein (0.70, 0.78, 0.86, 0.94, 1.02 and 1.10 g/kg·d) within Chinese habitual diets (proportions of good-quality protein were 40 to 45%). Subjects were randomly allocated equally into two groups (1.10, 0.86, 0.78 g/kg·d for group 1 and 1.02, 0.94, 0.70 g/kg·d for group 2 from period 1 to period 3 in turn). Adaptation days were from day 1 to day 6 and the isotope study day was day 7 in each period. Amino acid kinetics was measured in non-menstrual periods, based on the IAAO technique. Two indicators (rate of release of 13CO2 and rate of leucine oxidation) were used to estimate protein requirement by breakpoint analysis with a two-phase linear regression crossover model. RESULTS Mean and population safe protein requirements of Chinese habitual diets in non-menstrual periods from the rate of release of 13CO2 were 0.91 and 1.09 g/kg·d, respectively. And from the rate of leucine oxidation were 0.92 and 1.10 g/kg·d, respectively. CONCLUSIONS The protein requirement of young women on Chinese habitual diets in non-menstrual period was lower than the current protein reference intake for Chinese females. Further studies are necessary to explore female protein requirements during the whole menstrual cycle.