ABSTRACT
Tannins are compounds present in forage plants that, in small quantities in the diet of ruminants, produce protein complexes that promote passage through the rumen and use in the intestine. This study tested the hypothesis that beeswax (BW) and carnauba wax (CW) lipid matrices are effective encapsulants for creating bypass lysine (Lys) for ruminants, with tannin extracted from the Mimosa tenuiflora hay source enhancing material protection. Microencapsulated systems were made using the fusion-emulsification technique with a 2:1 shell-to-core ratio and four tannin levels (0%, 1%, 2%; 3%). The following eight treatments were tested: BWLys0%, BWLys1%, BWLys2%, BWLys3%, CWLys0%, CWLys1%, CWLys2%, and CWLys3%. Tannin inclusion improved microencapsulation yield and efficiency. CWLys3% had the highest microencapsulation efficiency and retained Lys. Lysine in BW and CW matrices showed higher thermal stability than in its free form. Material retention was greater in BW than CW. Rumen pH and temperature remained unaffected, indicating that BW and CW as the shell and tannin as the adjuvant are efficient encapsulants for Lys bypass production. The formulation CWLys3% is recommended as it is more efficient in protecting the lysin amino acid from rumen degradation.
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Probiogenomics can provide important insights bout probiotic candidate bacteria. This study aimed to perform an in-depth genomic characterization of the probiotic candidate Lactiplantibacillus plantarum CNPC024 to investigate its probiosis mechanisms, identify metabolic pathways that might benefit the host, and improve the safety assessment for this strain to be effectively used as a probiotic. After whole-genome sequencing in Illumina MiSeq platform, the de novo genome assembly resulted in a 3.2 Mb draft genome. According to the Average Nucleotide Identity (ANI) analysis with 46 randomly validated probiotic LAB belonging to the Lactobacillaceae family, the strain showed a 99% nucleotide identity with other L. plantarum probiotic species. We identified a set of determinants conferring tolerance to bile salts and low pH conditions, as well as temperature, oxidative and osmotic stressors via the glutathione-glutaredoxin system (Grxs). As a ßgalactosidaseproducing strain, it has the potential to be used in fermented dairy products for lactose-intolerant individuals. There were no significant hits for transferable antibiotic-resistance genes. We also identified gene clusters associated with production of bacteriocins (plantaricins E, F and K). Lastly, we detected metabolic pathways associated with the production of tryptophan-derived metabolites that could potentially modulate the host's immune responses.
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OBJECTIVES: This study aimed to investigate changes in the blood metabolic profiles of newborns with varying intrauterine growth conditions. Specifically, we analyzed the levels of amino acids, carnitine, and succinylacetone among full-term newborns, including small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). We aim to identify differential metabolites and metabolic pathways that may offer insights into clinical interventions. METHODS: A total of 5106 full-term newborns were included in the study. Blood samples were obtained from all newborns between 3 and 5 days after birth and analyzed using tandem mass spectrometry to detect blood metabolites. Subsequently, we screened for different metabolites and metabolic pathways among the groups using the MetaboAnalystR package (Version 1.0.1) in R software (R-3.6.0). RESULTS: The levels of blood amino acids and carnitine metabolism differed significantly among newborns with varying intrauterine growth conditions. Full-term SGA newborns exhibited a decrease in multiple amino acids and an increase in multiple carnitines, while full-term LGA newborns showed an increase in multiple amino acids and acylcarnitines. CONCLUSION: Continuous monitoring of the short-term and long-term growth and metabolic status of full-term SGA and LGA newborns is warranted with individualized dietary and nutritional adjustments to promote healthy growth in a timely manner. The findings of this research contribute to the broader understanding of SGA/LGA and shall inform future research on metabolomics, interventions, and long-term outcomes.
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The study investigated guanidinoacetic acid (GAA) supplementation with varying dietary digestible arginine (Arg) and glycine+serine (Gly+Ser) concentrations in the starter phase, exploring respective carry-over effects on growth performance, blood chemistry, incidence of pectoral myopathies and proximate composition in broilers. A total of 2,800 one-day-old male broiler chicks were distributed in a central composite design with 2 factors and double experimental mesh, represented by supplementation or omission of 0.6 g per kg of GAA, with a central point represented by 107% of Arg and 147% of Gly+Ser, 4 factorial points (combinations of Arg/Gly+Ser concentrations: 96.4/132.5%; 117.6/132.5%; 96.4/161.5%, and 117.6/132.5%), and 4 axial points (combinations of axial points estimated for Arg and Gly+Ser, with the central points of 92/147%; 122/147%; 107/126.5, and 107/167.5%), totaling 18 treatments, 4 repetitions to factorial and axial points, 24 replicates to the central point, and 25 birds per pen. Feed conversion ratio (FCR) from d 1 to 10 had a linear response (P = 0.009) for the decreasing Arg content and a quadratic response (P = 0.047) for Gly+Ser concentrations. Broilers supplemented GAA had lower FCR compared with nonsupplemented groups from d 1 to 10 (P = 0.048) and d 1 to 42 (P = 0.026). Aspartate aminotransferase (AST) exhibited increasing and decreasing linear effects as a function of Arg (P = 0.008) and Gly+Ser (P = 0.020) concentrations, respectively. Guanidinoacetic acid decreased serum AST (P = 0.028). Guanidinoacetic acid reduced moderate + severe (P = 0.039) and mild (P = 0.015) Wooden Breast scores. The occurrence of normal White Striping increased (P = 0.002), while severe score was reduced (P = 0.029) with GAA supplementation. In conclusion, increased digestible Arg:Lys and 14% and 6% above the recommendations (107% and 147%), respectively, provided improved FCR during the starter phase. Dietary GAA supplementation (0.6 g per kg) improved FCR, reduced severity of breast myopathies and appears to have reduced muscle damage in broilers fed plant-based diets.
Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena , Arginine , Chickens , Diet , Dietary Supplements , Glycine , Serine , Animals , Chickens/physiology , Chickens/growth & development , Glycine/analogs & derivatives , Glycine/administration & dosage , Glycine/pharmacology , Animal Feed/analysis , Arginine/administration & dosage , Arginine/pharmacology , Dietary Supplements/analysis , Diet/veterinary , Male , Animal Nutritional Physiological Phenomena/drug effects , Serine/administration & dosage , Serine/pharmacology , Random Allocation , Pectoralis MusclesABSTRACT
The objective was to conduct a systematic review to clarify the effects of l-arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin-like growth factor 1 (IGF-1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l-arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF-1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets.
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Guava is a fruit tree with high potential in the semi-arid region of northeast Brazil. However, qualitative and quantitative water scarcity is a limiting factor for the expansion of irrigated agriculture. Thus, it is necessary to use techniques to mitigate the effects of salt stress, such as foliar application of proline. The objective of this study was to evaluate the effect of foliar application of proline as a mitigator of salt stress effects on the morphophysiology of guava cv. Paluma. The experiment was carried out under field conditions at the 'Rolando Enrique Rivas Castellón' Experimental Farm in São Domingos, PB, Brazil, using a randomized block design in a 5 × 4 factorial scheme referring to five levels of electrical conductivity of irrigation water, ECw (0.8, 1.5, 2.2, 2.9, and 3.5 dS m-1) and four concentrations of proline (0, 8, 16, and 24 mM). Salinity above 0.8 dS m-1 compromised gas exchange, photosynthetic pigment synthesis, photochemical efficiency, and growth of guava plants at 360 days after transplanting. Foliar application of proline at a concentration of 24 mM mitigated the effect of salt stress on the relative water content, stomatal conductance, and carotenoid contents in plants irrigated with 3.6 dS m-1 water. Meanwhile, a proline concentration of up to 18 mM resulted in higher transpiration, CO2 assimilation rate, instantaneous carboxylation efficiency, and absolute growth rate in stem diameter under ECw of 0.8 dS m-1. Proline concentration of up to 24 mM increased the biosynthesis of photosynthetic pigments and the relative growth rate in stem diameter of guava in the period from 190 to 360 days after transplanting.
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The Brazilian Atlantic Forest, renowned for its exceptional species richness and high endemism, acts as a vital reservoir of terrestrial biodiversity, often referred to as a biodiversity hotspot. Consequently, there is an urgent need to restore this forest to safeguard certain species and to unravel the ecophysiological adaptations of others. This study aims to integrate some physiological parameters, including gas exchange and chlorophyll a fluorescence, with anatomical and metabolic techniques to elucidate how five different native species (Paubrasilia echinata, Chorisia glaziovii, Clusia nemorosa, Licania tomentosa, and Schinus terebinthifolius), each occupying distinct ecological niches, respond to seasonal variations in rainfall and their consequences. Our investigation has revealed that C. nemorosa and P. echinata exhibit robust mechanisms to mitigate the adverse effects of drought. In contrast, others demonstrate greater adaptability (e.g., S. terebinthifolia and C. glaziovii). In this context, exploring metabolic pathways has proven invaluable in comprehending the physiological strategies and their significance in species acclimatization. This study provides a comprehensive overview of the impact of water restrictions and their consequential effects on various species, defining the strategies each species uses to mitigate water privation during the dry season.
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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, metabolic perturbations associated with ASD, which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls in order to identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, an age and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and missing data imputation, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. The amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.
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N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide's secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu2+, Ni2+, and Zn2+, give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials.
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Asparagine is a non-essential amino acid crucial for protein biosynthesis and function, and therefore cell maintenance and growth. Furthermore, this amino acid has an important role in regulating several metabolic pathways, such as tricarboxylic acid cycle and the urea cycle. When compared to normal cells, tumor cells typically present a higher demand for asparagine, making it a compelling target for therapy. In this review article, we investigate different facets of asparagine bioavailability intricate role in malignant tumors raised from solid organs. We take a comprehensive look at asparagine synthetase expression and regulation in cancer, including the impact on tumor growth and metastasis. Moreover, we explore asparagine depletion through L-asparaginase as a potential therapeutic method for aggressive solid tumors, approaching different formulations of the enzyme and combinatory therapies. In summary, here we delve into studies about endogenous and exogenous asparagine availability in solid cancers, analyzing therapeutic implications and future challenges.
Subject(s)
Asparagine , Aspartate-Ammonia Ligase , Neoplasms , Humans , Asparagine/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/drug therapy , Aspartate-Ammonia Ligase/metabolism , Aspartate-Ammonia Ligase/genetics , Asparaginase/therapeutic use , AnimalsABSTRACT
INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.
Subject(s)
Amino Acids , Dietary Supplements , Milk Hypersensitivity , Animals , Cattle , Child, Preschool , Female , Humans , Infant , Male , Amino Acids/administration & dosage , Cross-Sectional Studies , Elimination Diets , Milk/immunology , Milk Proteins/administration & dosage , Milk Proteins/immunologyABSTRACT
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. Objective: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. Methods: We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica (ERAJ-2), which was a 1:1 age (±6 months)-and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Results: Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. Conclusions: These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.
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Researchers have reported the benefits of feeding rumen-protected methionine (RPM) during the peripartum on the health parameters of dairy cows. Rumen-protected Met has reportedly improved milk yield, milk components, and liver health, but the literature is scarce on its effects in commercial herds. Therefore, we aimed to determine the effects of feeding RPM (Smartamine M, Adisseo Inc., Antony, France) prepartum (8 g/cow per day) and postpartum (15 g/cow per day) on performance, metabolic profile, and culling rate of Holstein cows in a commercial herd. One hundred sixty-six (n = 166) Holstein cows, 58 nulliparous and 108 parous, were randomly assigned to 1 of 2 dietary treatments, consisting of TMR top-dressed with RPM (RPMet; 2.35% and 2.24% Met of MP for close-up and fresh cows, respectively) or without (control [CON] 2.03% and 1.89% Met of MP for close-up and fresh cows, respectively), fed from 21 ± 6 d prepartum until 16 ± 5 d postpartum. From 17 DIM until dry-off, all cows received RPMet. Daily milk yield was recorded, and milk samples were collected in the first and second weeks after calving to determine their composition. Blood samples were collected before the morning feeding on -14, -7, +1, +7, and +14 d relative to calving. Mortality and morbidity were recorded during the first 60 DIM. Cows supplemented with RPMet had greater milk yield during the first 16 DIM (31.76 vs. 30.37 kg/d; SEM = 1.04, respectively), and had greater milk fat content (4.45 vs. 4.10%; SEM = 0.11, respectively), but not milk total protein (3.47 vs. 3.39%; SEM = 0.04, respectively) and casein contents (2.74 vs. 2.66%; SEM = 0.04, respectively) than CON cows. Cows in RPMet had increased plasma Met concentrations than cows in CON (24.9 vs. 21.0 µmol/L; SEM = 1.2, respectively). Although morbidity was similar between treatments, the culling rate from calving until 60 DIM was lower for RPMet cows than for CON cows (2.4% vs. 12.1%; SEM = 0.02). In conclusion, cows receiving RPMet have greater milk yield, improved milk fat content, and a lower culling rate at 60 DIM than CON cows.
Subject(s)
Animal Feed , Diet , Lactation , Methionine , Milk , Peripartum Period , Rumen , Animals , Cattle , Methionine/metabolism , Methionine/administration & dosage , Female , Milk/chemistry , Milk/metabolism , Diet/veterinary , Rumen/metabolism , Animal Feed/analysisABSTRACT
The presence of different mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can be related to changes in coronavirus disease (COVID-19) infection. Besides, these viral alterations associated with factors such as massive number of positive cases, vaccination and reinfections can be important in the viral evolution process. As well as, mutations found at low frequencies may have a more neutral action and consequently be less inclined to negative selection, facilitating their spread through the population. Related to that, we aimed to present mutations that are possibly relevant in the process of viral evolution found in 115 SARS-CoV-2 sequences from samples of individuals residing in the metropolitan region of Porto Alegre in the state of Rio Grande do Sul, Brazil. The genome from clinical samples was sequenced using High-Throughput Sequencing (HTS) and analyzed using a workflow to map reads and find variations/SNPs. The samples were separated into 3 groups considering the sample lineage. Of the total number of analyzed sequences, 35 were from the Gamma lineage, 35 from Delta and 45 from Omicron. Amino acid changes present in frequencies lower than 80% of the reads in the sequences were evaluated. 11 common mutations among the samples were found in the Gamma lineage, 1 in the ORF1ab gene, 7 in the S gene, 2 in the ORF6 gene and 1 in the ORF7a gene. While in the Delta lineage, a total of 11 mutations distributed in the ORF1ab, S, ORF7a and N genes, 2, 7, 1 and 1 mutation were found in each gene, respectively. And finally, in the Omicron, 16 mutations were identified, 2 in the ORF1ab gene, 12 in the S gene and 2 in the M gene. In conclusion, we emphasize that genomic surveillance can be a useful tool to assess how mutations play a key role in virus adaptation, and its process of susceptibility to new hosts showing the possible signs of viral evolution.
Subject(s)
COVID-19 , Genome, Viral , Mutation , SARS-CoV-2 , SARS-CoV-2/genetics , Humans , COVID-19/virology , COVID-19/epidemiology , Brazil/epidemiology , Phylogeny , Evolution, MolecularABSTRACT
BACKGROUND & AIMS: Epidemiologic studies show high circulating Branched-chain amino acids (BCAA) are associated with excess body weight, impaired fasting glucose, insulin resistance, high blood pressure, and dyslipidemia. There is scarce data on the association between renal function and circulating levels of BCAA. Therefore, we aim to study this association in a sample of the Brazilian Longitudinal Study of Adults (ELSA-Brasil) METHODS: We analyzed participants who had at the baseline BCAA: valine, isoleucine, and leucine measured through nuclear magnetic resonance. The outcomes evaluated were estimated glomerular function (eGFR - CKD-EPI without race) and 12h-albumin-creatinine ratio (ACR). In addition, we built unadjusted and adjusted multivariable linear regression models to investigate the association between the BCAA (total and individual) and eGFR and ACR. RESULTS: We studied 4912 participants (age 51.7(±9.0) years, 53.4% women, 59.5% White (59.5%), 32.7% hypertension, and 18.2% diabetes). The mean BCAA level was 429.15 ± 87.15. The mean eGFR was 84.95 ± 15 ml/min/1.73 m2, and the median ACR was 6.5 (1.8-4920) mg/g. Descriptive analyses comparing eGFR stratified <60 ml/min/1.73 m2 and ACR≥30 mg/g demonstrate that BCAA levels are higher in patients with eGFR<60 and ACR ≥30. Regarding eGFR, an inverse association was detected with BCAA levels when adjusted for demographic variables, and it is not maintained after adjustments for other confounders. Also, a positive association was found for ACR≥30 mg/g, and BCAA levels, and this association is not confirmed after adjustments. CONCLUSIONS: BCAA levels were inversely associated with eGFR and positively associated with ACR. Further studies are necessary to allow the comprehension of those associations.
Subject(s)
Amino Acids, Branched-Chain , Glomerular Filtration Rate , Humans , Female , Male , Middle Aged , Brazil/epidemiology , Amino Acids, Branched-Chain/blood , Longitudinal Studies , Kidney/physiopathology , Adult , Creatinine/blood , Albuminuria/blood , AgedABSTRACT
Due to allergenic concerns, only pea, potato, and wheat proteins have been approved as alternatives for replacing animal-based fining agents in wines. In pursuit of other substitutes, this work aimed to determine the fining ability of amaranth (Amaranthus caudatus L.) proteins (AP) in red wine, compared to quinoa (Chenopodium quinoa Willd.) (QP) and a commercial pea protein. Phenolic and volatile composition, as well as color characteristics, were analyzed. AP was as effective as QP at decreasing condensed tannins, with AP at 50 g/hL being the most effective treatment (25.6% reduction). QP and AP produced a minor or no statistical change in the total anthocyanins and wine color intensity. They reduced the total ester concentration, but the total alcohols remained unchanged. The outcomes of AP and QP were similar, and sometimes better than the pea proteins, thus suggesting that they could be promising options for the development of novel fining agents.
Subject(s)
Amaranthus , Chenopodium quinoa , Plant Proteins , Wine , Amaranthus/chemistry , Chenopodium quinoa/chemistry , Plant Proteins/chemistry , Plant Proteins/analysis , Wine/analysis , Phenols/chemistry , Phenols/analysis , Plant Extracts/chemistry , ColorABSTRACT
In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034â µM in A-431, 2.67â µM in MCF-7, and 3.64â µM in AGS) without showing activity on the non-tumorigenic cell line (>100â µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an inâ vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50â ns.
Subject(s)
Amino Acids , Antineoplastic Agents , Cyclooxygenase 2 , Drug Screening Assays, Antitumor , ErbB Receptors , Ibuprofen , Quinazolines , Ibuprofen/pharmacology , Ibuprofen/chemistry , Ibuprofen/chemical synthesis , Humans , Quinazolines/pharmacology , Quinazolines/chemistry , Quinazolines/chemical synthesis , Cyclooxygenase 2/metabolism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Amino Acids/chemistry , Amino Acids/pharmacology , Amino Acids/chemical synthesis , Molecular Structure , Cell Line, Tumor , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Tetradecanoylphorbol Acetate/pharmacology , Cell Proliferation/drug effects , Animals , Dose-Response Relationship, Drug , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Cell Survival/drug effectsABSTRACT
Hypertension is an important risk factor concomitant with cardiovascular disease (CVD) states, which is why we set out to evaluate Californian red worm hydrolysates on antihypertensive activity both in vitro, ex vivo, using rabbit aortic rings and in vivo using hypertensive induced rats. The worms were manually separated, washed with water, purged for 4 h with 4 % sodium bicarbonate, sacrificed with 7 % saline, and finally washed with drinking water. The in vitro antihypertensive capacity was performed by measuring angiotensin-converting enzyme inhibition; for the ex vivo assays, rabbit aorta was used to measure relaxation; for the in vivo assays, rats with induced hypertension were used to perform acute (hypotension) and chronic assays, using captopril as a control in all assays. With respect to angiotensin-converting enzyme (ACE) inhibition, the EC50 value of the worm hydrolysate was found to be 358 ppm; with respect to the analysis in aortic rings, it was found that the mechanisms of action of the hydrolysate are endothelium-dependent, presenting a maximum relaxation of 35 %. With respect to the in vivo assays, the hypotensive test showed that the hydrolysate can reduce blood pressure by up to 32 % in only 2 h, while the chronic analysis showed that the hydrolysate at 150 ppm did not present statistically significant differences with the control (captopril) during the 15 days of analysis. The Red Californian earthworm hydrolysate presents bioactive compounds identified with antihypertensive activities in vitro, ex vivo and in vivo in different isolated and animal models. The study demonstrates the efficacy of the hydrolysate to be used as an alternative in the treatment and prevention of hypertension, and it can be implemented in functional foods or nutraceutical foods. Antihypertensive peptides, particularly those that inhibit angiotensin-converting enzyme (ACE), hold significant importance in medical research, specifically in the context of cardiovascular disease treatment, particularly hypertension. The focus on these peptides and the potential implications of their results in medical research can be summarized through several key points: 1) Mechanisms of Action-Antihypertensive peptides function by inhibiting ACE or renin, crucial enzymes in blood pressure regulation. 2)Alternatives to Synthetic Drugs, 3) Additional Health Benefits, and various other factors.
ABSTRACT
Zinc (Zn) is an essential micronutrient that plays a crucial role in fish development and physiology. This study aimed to evaluate the effects on growth and health in Nile tilapia (Oreochromis niloticus) supplemented with graded levels of zinc amino acid complex (Zn-AA) and subjected to transport stress. Nile tilapia (21.78 ± 0.17 g; (n = 12 fish per tank; stocking density of 1.045 kg- 3) were fed with 0, 25, 50, 75, or 100 mg Zn-AA kg- 1 (equivalent to 77.49, 102.69, 127.89, 153.09, or 178.29 mg Zn kg- 1) in extruded diets (280 g kg- 1 digestible protein; isoproteic and isocaloric) for 60 days. At the end of the experimental period, after growth performance measurements, the fish were transported by car for 3 h, and blood collection was performed. The linear regression showed that the best growth performance (final weight, final biomass, weight gain, specific growth rate, and feed intake) was found in fish fed with 100 mg Zn-AA kg diet- 1 (p < 0.05). The increased dietary Zn-AA increased linearly plasma triglyceride levels, hemoglobin, mean corpuscular hemoglobin, and leukocyte values and reduced plasma total protein, cholesterol (total and LDL), and aspartate aminotransferase levels (p < 0.05). According to quadratic regression, the highest plasma glucose and alanine aminotransferase values were found in the control group (p < 0.05). In conclusion, under the conditions of this study, 100 mg Zn-AA kg diet- 1 is recommended for Nile tilapia as it can improve their growth, metabolism, physiology, and immunity.
Subject(s)
Cichlids , Zinc , Animals , Zinc/metabolism , Amino Acids , Dietary Supplements , Diet/veterinary , Animal Feed/analysisABSTRACT
PURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression. EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.