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1.
Open Biol ; 14(8): 240093, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39106944

ABSTRACT

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.


Subject(s)
Drosophila melanogaster , Nicotine , Stress, Physiological , Animals , Drosophila melanogaster/drug effects , Female , Male , Nicotine/pharmacology , Stress, Physiological/drug effects , Oxidative Stress/drug effects , Amino Acids/pharmacology , Amino Acids/metabolism , Isoleucine/pharmacology
2.
Clinics (Sao Paulo) ; 79: 100459, 2024.
Article in English | MEDLINE | ID: mdl-39098147

ABSTRACT

OBJECTIVE: Sjögren's Syndrome (SS) is a chronic inflammatory autoimmune exocrinopathy, and although, the role of metabolism in the autoimmune responses has been discussed in diseases such as lupus erythematosus, rheumatoid arthritis, psoriasis and scleroderma. There is a lack of information regarding the metabolic implications of SS. Considering that the disease affects primarily salivary glands; the aim of this study is to evaluate the metabolic changes in the salivary glands' microenvironment using a targeted metabolomics approach. METHODS: The saliva from 10 patients diagnosed with SS by the American-European consensus and 10 healthy volunteers was analyzed in an Ultra-high Performance Liquid Chromatograph Coupled Mass Spectrometry (UPLC-MS). RESULTS: The results showed an increased concentration in SS of metabolites involved in oxidative stress such as lactate, alanine and malate, and amino acids involved in the growth and proliferation of T-cells, such as arginine, leucine valine and isoleucine. CONCLUSIONS: These results revealed that is possible to differentiate the metabolic profile of SS and healthy individuals using a small amount of saliva, which in its turn may reflect the cellular changes observed in the microenvironments of damaged salivary glands from these patients.


Subject(s)
Metabolomics , Saliva , Sjogren's Syndrome , Humans , Sjogren's Syndrome/metabolism , Saliva/chemistry , Saliva/metabolism , Metabolomics/methods , Female , Middle Aged , Case-Control Studies , Adult , Chromatography, High Pressure Liquid , Mass Spectrometry , Male , Oxidative Stress/physiology , Amino Acids/analysis , Amino Acids/metabolism , Aged
3.
Molecules ; 29(15)2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39124955

ABSTRACT

Sea buckthorn leaves (SBT_LVs) form notable by-product during harvesting and post-harvest management of the berries. It is already known that sea buckthorn berries are important for their chemical composition and based on this, they occupy a wide field in nutrition. SBT_LVs also have a rich chemical composition, like the berries. The aim of this study was to describe these by-products in the context of protein and complex carbohydrates-dietary fiber fractions, including qualitative and quantitative composition of amino acids. Proximate composition, amino acids, nutritional values of the protein, and dietary fiber fractions of SBT_LVs of four cultivars (cvs.) Ascola, Habego, Hergo, and Leikora were assessed. SBT_LVs from different years of the study had statistically different levels of crude protein, ether extract, crude ash, and nitrogen-free extract (NFE), confirming that the quality of the raw material (leaves) can be significantly modified by habitat conditions. The largest fraction of dietary fiber was neutral detergent fiber (NDF), including the sum of hemicellulose, cellulose, and lignin, followed by the acid detergent fiber fraction (ADF), consisting of lignin and cellulose. The content of essential amino acids in SBT_LV protein was high. Overall, this study confirms that SBT_LVs hold promise as a valuable resource for use as a food ingredient, functional food, and dietary supplement for both humans and animals.


Subject(s)
Amino Acids , Dietary Fiber , Hippophae , Nutritive Value , Plant Leaves , Hippophae/chemistry , Plant Leaves/chemistry , Dietary Fiber/analysis , Amino Acids/analysis , Amino Acids/chemistry , Plant Proteins/analysis
4.
Molecules ; 29(15)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39125003

ABSTRACT

With the global population projected to reach nine billion by 2050, the search for alternative protein sources has become critical. This study evaluated the digestibility of cricket protein powder compared with that of whey protein powder. Cricket protein powder had a slightly lower protein content but higher fat content than whey protein powder. Although both contained all essential amino acids, their quantities varied. The most abundant essential amino acid was leucine in both samples. The essential amino acid index (EAAI) for cricket protein powder reached 79% when utilising crude protein for calculation. When using the amino acid sum calculation method, it increased by nearly 13%. The EAAI for whey protein was then 94% when calculated based on crude protein, with a slight increase observed when using the amino acid sum calculation method. Cricket protein exhibited a gradual increase in digestibility during intestinal digestion, reaching nearly 80%, whereas whey protein digestibility surpassed 97%. Despite the lower digestibility of cricket protein compared with whey protein, it remains sufficiently high for consideration as a valuable protein source. This study highlights the potential of cricket proteins and underscores the importance of assessing their protein content and digestibility in evaluating their nutritional value.


Subject(s)
Digestion , Powders , Whey Proteins , Whey Proteins/chemistry , Whey Proteins/metabolism , Animals , Amino Acids/metabolism , Amino Acids/chemistry , Gryllidae/metabolism , Gryllidae/chemistry , Nutritive Value , Amino Acids, Essential/metabolism
5.
Molecules ; 29(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39125083

ABSTRACT

The growing world population necessitates the implementation of appropriate processing technologies for edible insects. The objective of this study was to examine the impact of distinct drying techniques, including convective drying at 70 °C (70CD) and 90 °C (90CD) and freeze-drying (FD), on the drying kinetics, physical characteristics (water activity, color), chemical characteristics (chemical composition, amino acid profile, oil properties, total polyphenol content and antioxidant activity, mineral composition, FTIR), and presence of hazards (allergens, microorganisms) of blanched yellow mealworm larvae. The freeze-drying process results in greater lightness and reduced moisture content and water activity. The study demonstrated that the freeze-dried insects exhibited lower contents of protein and essential amino acids as compared to the convective-dried insects. The lowest content of total polyphenols was found in the freeze-dried yellow mealworm larvae; however, the highest antioxidant activity was determined for those insects. Although the oil isolated from the freeze-dried insects exhibited the lowest acid and peroxide values, it proved to have the lowest PUFA content and oxidative stability. All the samples met the microbiological criteria for dried insects. The results of the study demonstrate that a high temperature during the CD method does not result in the anticipated undesirable changes. It appears that freeze-drying is not the optimal method for preserving the nutritional value of insects, particularly with regard to the quality of protein and oil.


Subject(s)
Antioxidants , Desiccation , Freeze Drying , Larva , Tenebrio , Animals , Larva/chemistry , Tenebrio/chemistry , Freeze Drying/methods , Antioxidants/chemistry , Antioxidants/analysis , Desiccation/methods , Polyphenols/analysis , Polyphenols/chemistry , Amino Acids/analysis , Amino Acids/chemistry
6.
Food Res Int ; 192: 114759, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39147534

ABSTRACT

To investigate the quality of different ozone-oxidized surimi gels and their in vitro digestion and absorption characteristics, surimi rinsed with different concentrations of ozonated water (0, 8, 26 mg/L) were prepared. Then, the degree of oxidation and gel structure of surimi were determined, the in vitro digestion and absorption of the gels were simulated, and the digestion and absorption products were analyzed by LC-MS/MS. The results showed that the quality of surimi gels was improved after proper ozone oxidation. After ozone water rinsing, the dry matter digestibility, peptide, and amino acid content increased, and the changes of all three were in line with the Logistic kinetic model (R2 = 0.95-0.99). Caco-2 cell absorption experiments showed that the absorption rate of peptides and amino acids decreased after ozone water rinsing. In summary, ozone oxidation can promote the digestion of surimi gels, but it also reduces the absorption of peptides and amino acids by Caco-2 cells. This study provides a reference for the application of ozone in the food field.


Subject(s)
Carps , Digestion , Fish Products , Oxidation-Reduction , Ozone , Ozone/chemistry , Caco-2 Cells , Animals , Humans , Fish Products/analysis , Carps/metabolism , Gels/chemistry , Amino Acids/metabolism , Amino Acids/analysis , Tandem Mass Spectrometry , Intestinal Absorption , Peptides
7.
Food Res Int ; 192: 114749, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39147554

ABSTRACT

This research aims to assess the effect of amino acids as lipid antioxidants in reducing the formation of volatile aldehydes in frying oil. Methionine, histidine, and glycine at concentrations of 2.5, 5, and 10 mM were added to high oleic sunflower oil (HOSO) to investigate their effects on the distribution and formation of saturated, monounsaturated, and polyunsaturated volatile aldehydes. The results showed that the proportion of saturated volatile aldehydes was greater than that of unsaturated ones; Methionine exhibited the best inhibitory effect, after 12 h of frying, 10 mM methionine reduced the content of saturated volatile aldehydes by 24.21 %, monounsaturated by 52.4 %, and polyunsaturated by 54.73 % compared to the control. Methionine's sulfur-containing side chain was also proven to have strong antioxidant activity. Combined with the results of this study, this can also provide insights for using amino acids as lipid antioxidants.


Subject(s)
Aldehydes , Amino Acids , Antioxidants , Cooking , Hot Temperature , Sunflower Oil , Sunflower Oil/chemistry , Aldehydes/analysis , Antioxidants/analysis , Amino Acids/analysis , Methionine/chemistry , Plant Oils/chemistry , Volatile Organic Compounds/analysis , Histidine/analysis , Histidine/chemistry , Oleic Acid/analysis , Glycine/chemistry
8.
Wei Sheng Yan Jiu ; 53(4): 600-607, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39155228

ABSTRACT

OBJECTIVE: To analyze the nutrient composition and nutritional value evaluation of 5 potatoes in Anqing City. METHODS: According to the requirements of the Technical Manual for Food Composition Monitoring Projects, 5 types of potato samples were collected from Anqing City, Anhui Province. National standard detection method were used to determine the nutritional components such as water, ash, protein, fat, dietary fiber, sugar, minerals, vitamins, and amino acids in the samples. The index of nutritional quality(INQ) method was used to evaluate proteins, vitamins, and minerals, and the amino acid scoring standard mode(FAO/WHO mode) was used to evaluate the nutritional value of amino acids. RESULTS: Among the 5 types of potatoes, purple potato had the highest protein(2.3 g/100 g) and dietary fiber content(3.6 g/100 g). Sweet potato(red) had the highest carotene content(4003 µg/100 g), sweet potato(white) had the highest content of vitamin C(15.4 mg/100 g). Sugar in potatoes mainly existed in three forms: fructose, glucose, and sucrose; Purple potatoes had the highest levels of calcium(47 mg/100 g) and phosphorus(74 mg/100 g), respectively. Potatoes(white) had the highest content of potassium(401 mg/100 g), while sweet potatoes(red) had the highest content of magnesium(31 mg/100 g). Sodium(104.0 mg/100 g), iron(0.9 mg/100 g), copper(0.17 mg/100 g), and manganese(0.40 mg/100 g) had the highest content in sweet potatoes(white). The Na/K ratio range of the 5 potato varieties was 0.003-0.456, and the INQ of phosphorus, potassium, magnesium, copper, and manganese were greater than 1. The detection result of 5 potatoes all contain 18 amino acids, and aspartic acid was the highest. The amino acid score(AAS) was 0.29-1.35, and the ratio coefficient(RC) was 0.47-1.69. CONCLUSION: The 5 types of potatoes are rich in dietary fiber, vitamin C and minerals, and belong to the high potassium and low sodium type of food. Potatoes can meet the daily needs of the human body for phosphorus, potassium, magnesium copper, and manganese elements. Lysine is rich in content and can be used as a nutritional supplement for grains. The AAS score and RC are close to 1, and the AAS evaluation mode is closer to the human amino acid composition mode, which can meet the daily needs of the human body for this essential amino acid.


Subject(s)
Dietary Fiber , Minerals , Nutritive Value , Solanum tuberosum , Solanum tuberosum/chemistry , Dietary Fiber/analysis , China , Minerals/analysis , Vitamins/analysis , Food Analysis , Amino Acids/analysis , Ascorbic Acid/analysis , Phosphorus/analysis
9.
BMC Endocr Disord ; 24(1): 142, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107770

ABSTRACT

BACKGROUND: Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5-10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage. METHODS: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group. RESULTS: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group. CONCLUSION: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.


Subject(s)
Amino Acids , Blastocyst , Embryonic Development , Glutathione , Polycystic Ovary Syndrome , Animals , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/pathology , Female , Mice , Blastocyst/metabolism , Embryonic Development/genetics , Glutathione/metabolism , Amino Acids/metabolism , Sequence Analysis, RNA , Disease Models, Animal , Gene Expression Regulation, Developmental
10.
Article in Chinese | MEDLINE | ID: mdl-39118510

ABSTRACT

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group(P<0.05). Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group(P=0.024). Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ(P=0.026). In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma(P=0.041). The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old(P=0.033). The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history(P=0.033). The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption(P=0.003). ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma(AUC=0.855). However, citrulline alone had the highest specificity(0.830) in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group(P<0.001). The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.


Subject(s)
Amino Acids , Carcinoma, Squamous Cell , Laryngeal Neoplasms , Humans , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/diagnosis , Male , Female , Middle Aged , Amino Acids/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/diagnosis , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , ROC Curve , Case-Control Studies
11.
Braz J Biol ; 84: e285964, 2024.
Article in English | MEDLINE | ID: mdl-39109732

ABSTRACT

The article presents the results of the study of biochemical composition of sheep milk in the summer lactation period for 4 sheep breeds. According to research results, 18 amino acids were found in sheep milk. During the summer lactation period, the amount of polyunsaturated fatty acids, both the Ordabasy breed and the South Kazakh merino exhibit higher levels (ranging from 6349 to 6989) compared to the Kazakh fine-fleeced and meat Merino breeds (ranging from 5835 to 5500). When analyzing sheep milk, a tendency towards a higher content of vitamin A (59.91 µg/100 g) and B6 (73.0 µg/100 g) was noted. The highest calcium content was found in the milk of the Kazakh fine-fleeced sheep, while the lowest was observed in the South Kazakh merino breed. Better milk productivity, along with increased fat and protein content, has been noted in sheep of the Ordabasy and South Kazakh merino breeds.


Subject(s)
Lactation , Milk , Seasons , Animals , Milk/chemistry , Lactation/physiology , Female , Sheep , Amino Acids/analysis
13.
Sci Rep ; 14(1): 18608, 2024 08 10.
Article in English | MEDLINE | ID: mdl-39127724

ABSTRACT

This study spanned 6 years and 4 generations, involving the progressive crossbreeding of South African Kalahari Goat (SK) and Guizhou Black Goat (GB) over three generations, followed by cross fixation F3 with F1 in the fourth generation, accompanied by the use of molecular markers technology to select a high fertility population, resulting in the creation of a hybrid goat, BKF4 (11/16 SK lineage and 5/16 GB lineage). A comparative evaluation of the BKF4 hybrid breed and its parental breeds was conducted. Reproductive and production parameters of GB, SK, and BKF4 goat groups were monitored, including lambing rate (LR), survival rate (SR), daily weight gain at 3 months of age (DWG), and adult body weight (ABW) (n = 110, 106, 112 per group). In addition, dressing percentage (DP) (n = 12 per group) and analyses of amino acids (n = 8, 6, 10 per group) and fatty acids (n = 6 per group) were conducted to evaluate meat quality indicators. Results: (1) Reproductive and production performance: The index of LR reached 199%, significantly higher than GB and SK (p ≤ 0.001), with a SR of 95.0%, markedly higher than SK (p ≤ 0.001); DWG was 276.5 g, ABW reached 56.6 kg and with a dressing percentage (DP) of 54.5%, they are significantly surpassing GB (p ≤ 0.001). (2) Regarding meat quality: pH45-value and crude protein content (CP) increased, while intramuscular fat content increased compared to GB and ash content decreased. The amino acid composition was similar to GB, but the taste was more similar to SK. However, there were some negative impacts on fatty acid composition and functionality. (3) PCA analysis revealed that: BKF4 exhibited superior meat quality compared to GB and SK, influenced by two key factors contributing 83.49% and 16.51% to the explained variance, respectively. The key factors affecting meat quality include intramuscular fat (IMF), nutrient index (NI), PUFAs/MUFAs, n-6FAs, and drip loss (DL).


Subject(s)
Goats , Meat , Animals , Goats/genetics , Meat/analysis , Meat/standards , Male , Female , Hybridization, Genetic , Fatty Acids/metabolism , Fatty Acids/analysis , South Africa , Breeding , Amino Acids/analysis , Amino Acids/metabolism , Reproduction , Body Weight
14.
Metabolomics ; 20(5): 92, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096437

ABSTRACT

INTRODUCTION: The human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches. OBJECTIVE: This study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics. METHODS: Urine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups. RESULTS: The study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients. CONCLUSION: The metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.


Subject(s)
Amino Acids , Carnitine , Coinfection , HIV Infections , Metabolomics , Tuberculosis , Adult , Female , Humans , Male , Middle Aged , Amino Acids/urine , Amino Acids/metabolism , Carnitine/analogs & derivatives , Carnitine/urine , Carnitine/metabolism , Chromatography, High Pressure Liquid/methods , Coinfection/urine , Coinfection/metabolism , HIV Infections/complications , HIV Infections/urine , HIV Infections/metabolism , Liquid Chromatography-Mass Spectrometry/methods , Metabolomics/methods , Tandem Mass Spectrometry/methods , Tuberculosis/urine , Tuberculosis/metabolism
15.
Article in English | MEDLINE | ID: mdl-39099475

ABSTRACT

The interplay between the tumor cells and their microenvironments is as inseparable as the relationship between "seeds" and "soil." The tumor microenvironments (TMEs) exacerbate malignancy by enriching malignant cell subclones, generating extracellular matrices, and recruiting immunosuppressive cells, thereby diminishing the efficacy of clinical therapies. Modulating TMEs has emerged as a promising strategy to enhance cancer therapy. However, the existing drugs used in clinical settings do not target the TMEs specifically, underscoring the urgent need for advanced strategies. Bioactive materials present unique opportunities for modulating TMEs. Poly(amino acid)s with precisely controllable structures and properties offer exceptional characteristics, such as diverse structural units, excellent biosafety, ease of modification, sensitive biological responsiveness, and unique secondary structures. These attributes hold significant potential for the modulation of TMEs and clinical applications further. Consequently, developing bioactive poly(amino acid)s capable of modulating the TMEs by elucidating structure-activity relationships and mechanisms is a promising approach for innovative clinical oncology therapy. This review summarizes the recent progress of our research team in developing bioactive poly(amino acid)s for multi-modal tumor therapy. First, a brief overview of poly(amino acid) synthesis and their advantages as nanocarriers is provided. Subsequently, the pioneering research of our research group on synthesizing the biologically responsive, dynamically allosteric, and immunologically effective poly(amino acid)s are highlighted. These poly(amino acid)s are designed to enhance tumor therapy by modulating the intracellular, extracellular matrix, and stromal cell microenvironments. Finally, the future development of poly(amino acid)s is discussed. This review will guide and inspire the construction of bioactive poly(amino acid)s with promising clinical applications in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Peptide-Based Structures.


Subject(s)
Amino Acids , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/drug therapy , Amino Acids/chemistry , Amino Acids/therapeutic use , Animals , Tumor Microenvironment/drug effects , Mice , Polymers/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
16.
Nat Commun ; 15(1): 6766, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117651

ABSTRACT

Live vaccines are ideal for inducing immunity but suffer from the need to attenuate their pathogenicity or replication to preclude the possibility of escape. Unnatural amino acids (UAAs) provide a strategy to engineer stringent auxotrophies, yielding conditionally replication incompetent live bacteria with excellent safety profiles. Here, we engineer Pseudomonas aeruginosa to maintain auxotrophy for the UAA p-benzoyl-L-phenylalanine (BzF) through its incorporation into the essential protein DnaN. In vivo evolution using an Escherichia coli-based two-hybrid selection system enabled engineering of a mutant DnaN homodimeric interface completely dependent on a BzF-specific interaction. This engineered strain, Pa Vaccine, exhibits undetectable escape frequency (<10-11) and shows excellent safety in naïve mice. Animals vaccinated via intranasal or intraperitoneal routes are protected from lethal challenge with pathogenic P. aeruginosa PA14. These results establish UAA-auxotrophic bacteria as promising candidates for bacterial vaccine therapy and outline a platform for expanding this technology to diverse bacterial pathogens.


Subject(s)
Pseudomonas Infections , Pseudomonas Vaccines , Pseudomonas aeruginosa , Animals , Pseudomonas aeruginosa/immunology , Pseudomonas aeruginosa/genetics , Pseudomonas Infections/prevention & control , Pseudomonas Infections/immunology , Pseudomonas Infections/microbiology , Mice , Female , Pseudomonas Vaccines/immunology , Pseudomonas Vaccines/genetics , Amino Acids , Phenylalanine/analogs & derivatives , Escherichia coli/immunology , Escherichia coli/genetics , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Mice, Inbred BALB C
17.
Int J Mol Sci ; 25(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39126047

ABSTRACT

Plants communicate underground by secreting multiple amino acids (AAs) through their roots, triggering defense mechanisms against cadmium (Cd) stress. However, the specific roles of the individual AAs in Cd translocation and detoxification remain unclear. This study investigated how exogenous AAs influence Cd movement from the roots to the shoots in Cd-resistant and Cd-sensitive Chinese cabbage cultivars (Jingcui 60 and 16-7 cultivars). The results showed that methionine (Met) and cysteine (Cys) reduced Cd concentrations in the shoots of Jingcui 60 by approximately 44% and 52%, and in 16-7 by approximately 43% and 32%, respectively, compared to plants treated with Cd alone. However, threonine (Thr) and aspartic acid (Asp) did not show similar effects. Subcellular Cd distribution analysis revealed that AA supplementation increased Cd uptake in the roots, with Jingcui 60 preferentially storing more Cd in the cell wall, whereas the 16-7 cultivar exhibited higher Cd concentrations in the organelles. Moreover, Met and Cys promoted the formation of Cd-phosphate in the roots of Jingcui 60 and Cd-oxalate in the 16-7 cultivar, respectively. Further analysis showed that exogenous Cys inhibited Cd transport to the xylem by downregulating the expression of HMA2 in the roots of both cultivars, and HMA4 in the 16-7 cultivar. These findings provide insights into the influence of exogenous AAs on Cd partitioning and detoxification in Chinese cabbage plants.


Subject(s)
Amino Acids , Brassica , Cadmium , Plant Roots , Cadmium/toxicity , Cadmium/metabolism , Brassica/metabolism , Brassica/drug effects , Amino Acids/metabolism , Plant Roots/metabolism , Plant Roots/drug effects , Biological Transport , Plant Shoots/metabolism , Plant Shoots/drug effects , Gene Expression Regulation, Plant/drug effects , Plant Proteins/metabolism , Plant Proteins/genetics
18.
Proc Natl Acad Sci U S A ; 121(35): e2322755121, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39163330

ABSTRACT

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the "GATOR" supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface.


Subject(s)
Amino Acids , Lysosomes , Mechanistic Target of Rapamycin Complex 1 , Monomeric GTP-Binding Proteins , Nutrients , Signal Transduction , Mechanistic Target of Rapamycin Complex 1/metabolism , Lysosomes/metabolism , Humans , Amino Acids/metabolism , Monomeric GTP-Binding Proteins/metabolism , Nutrients/metabolism , Animals , Mice , Adaptor Proteins, Signal Transducing/metabolism , HEK293 Cells
19.
Funct Plant Biol ; 512024 Aug.
Article in English | MEDLINE | ID: mdl-39163496

ABSTRACT

Priming enables plants to respond more promptly, minimise damage, and survive subsequent stress events. Here, we aimed to assess the efficacy of priming and cross-priming in mitigating the stress caused by waterlogging and/or dehydration in soybeans (Glycine max ). Soybean plants were cultivated in a greenhouse in plastic pots in which soil moisture was maintained at pot capacity through irrigation. The first stress was applied in plants at the vegetative stage for 5days and involved either dehydration or waterlogging, depending on the treatment. Subsequently, the plants were irrigated or drained and maintained at pot capacity until the second stress. For the second stress, the conditions were repeated in plants at the reproductive stage. We then evaluated the levels of hydrogen peroxide (H2 O2 ), lipid peroxidation, total soluble sugars (TSS), amino acids, proline, and starch, and the activity of antioxidant, fermentative, and aminotransferase enzymes. Under waterlogging and dehydration, priming and cross-priming significantly increased the activity of antioxidant enzymes and the levels of TSS, amino acids, and proline while reducing H2 O2 concentration and lipid peroxidation. Under waterlogging, priming suppressed fermentative activity and increased carbohydrate content. This demonstrates that soybean plants activate their defence systems more promptly when subjected to priming.


Subject(s)
Glycine max , Hydrogen Peroxide , Lipid Peroxidation , Stress, Physiological , Water , Glycine max/metabolism , Hydrogen Peroxide/metabolism , Water/metabolism , Dehydration , Amino Acids/metabolism , Antioxidants/metabolism , Proline/metabolism
20.
Funct Plant Biol ; 512024 Aug.
Article in English | MEDLINE | ID: mdl-39163498

ABSTRACT

The synthesis and differential allocation of reserve compounds is an important adaptive mechanism that enables species to resprout in fire-prone ecosystems. The analysis of compound allocation dynamics (differential accumulation of compounds between plant organs) provides insights into plant responses to disturbances. The aim was to quantify reserves in eight legume species from Cerrado open savannas with high fire frequency in order to investigate the patterns of allocation and distribution of compounds between leaves and underground organs, drawing ecophysiological inferences. The species were collected in 'campo sujo' areas of the Cerrado. Leaves and underground organs (xylopodium, taproot tubers) were subjected to physiological analyses. Overall, underground organs were characterised by greater deposits of carbohydrates, mainly soluble sugars, and also with the accumulation of proteins and amino acids. This suggests that nitrogen reserves, as well as carbohydrates, may have an ecophysiological function in response to fire, being allocated to the underground organs. Phenols were mainly evident in leaves, but a morphophysiological pattern was identified, where the two species with taproot tubers tended to concentrate more phenols in the underground portion compared to species with xylopodium, possibly due to functional differences between these organs. Such data allow inferring relevant ecophysiological dynamics in legumes from open savannas.


Subject(s)
Fabaceae , Plant Leaves , Fabaceae/metabolism , Plant Leaves/metabolism , Fires , Grassland , Brazil , Phenols/metabolism , Plant Roots/metabolism , Amino Acids/metabolism , Plant Tubers/metabolism
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