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1.
Braz. j. biol ; 84: e250936, 2024. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345557

RESUMO

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.


Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.


Assuntos
Animais , Masculino , Ratos , Queimaduras/tratamento farmacológico , Glutamina , Ratos Wistar , Dipeptídeos , Modelos Animais de Doenças , Aminoácidos
2.
J Exp Clin Cancer Res ; 42(1): 36, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36710342

RESUMO

BACKGROUND: Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis. METHODS: A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets. RESULTS: At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis. CONCLUSION: In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.


Assuntos
Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Neoplasias Gástricas , Humanos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Estudo de Associação Genômica Ampla , Neoplasias Gástricas/genética , Colesterol/metabolismo , Mutação , Aminoácidos/genética
3.
J Environ Manage ; 330: 117060, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36587550

RESUMO

Chrysanthemum waste (CW) is an agricultural and industrial by-product produced during chrysanthemum harvesting, drying, preservation, and deep processing. Although it is nutritious, most CW is discarded, wasting resources and contributing to serious environmental problems. This work explored a solid-state fermentation (SSF) strategy to improve CW quality for use as an alternative feed ingredient. Orthogonal experiment showed that the optimal conditions for fermented chrysanthemum waste (FCW) were: CW to cornmeal mass ratio of 9:1, Pediococcus cellaris + Candida tropicalis + Bacillus amyloliquefaciens proportions of 2:2:1, inoculation amount of 6%, and fermentation time of 10 d. Compared with the control group, FCW significantly increased the contents of crude protein, ether extract, crude fiber, acid detergent fiber, neutral detergent fiber, ash, calcium, phosphorus, and total flavonoids (p < 0.01), and significantly decreased pH and saponin content (p < 0.01). SSF improved the free and hydrolyzed amino acid profiles of FCW, increased the content of flavor amino acids, and improved the amino acid composition of FCW protein. Overall, SSF improved CW nutritional quality. FCW shows potential use as a feed ingredient, and SSF helps reduce the waste of chrysanthemum processing.


Assuntos
Aminoácidos , Detergentes , Fermentação , Amido , Ração Animal/análise
4.
Sci Total Environ ; 865: 161122, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36587690

RESUMO

Fluorene (Flu) occurs widely in various environments and its toxicity to organisms is well-known. However, the impact of Flu on complicated biochemical processes involving functional microbial community has been reported rarely. In this study, the facilitation of Flu on the volatile fatty acids (VFAs) generation executed by acidogenic microbial population during sludge acidogenic fermentation (37 °C, SRT = 8 d, pH = 10.0) was investigated. The accumulation of VFAs (particularly acetic acid) increased initially and then declined with the increasing of Flu concentration (0-500 mg/kg dry sludge), which reached a maximum (3211.1 mg COD/L) as Flu content was 200 mg/kg dry sludge. The Flu-enhanced VFAs production was primarily attributed to the shift of hydrolysis/acidification, as well as the corresponding functional microbial community and the activity of enzymes. Based on the metagenomics analysis, the conversion of organic substrates, i.e. amino acid and monosaccharide, into VFAs embraced in hydrolysis/acidification shaped by Flu was constructed at the genetic level. The relative abundances of genes included in aminotransfer and deamination process of amino acid and glycolysis of monosaccharide into VFA-precursors (pyruvate, acetyl-CoA and propionyl-CoA), and the further formation of VFAs were improved due to the Flu presence. This study shed light on the Flu-affected microbial processes at the molecular biology level during acidogenic fermentation and was of great significance in resource recovery of sludge containing persistent organic pollutants.


Assuntos
Aminoácidos , Esgotos , Fermentação , Esgotos/química , Monossacarídeos , Ácidos Graxos Voláteis , Ácidos , Fluorenos , Concentração de Íons de Hidrogênio , Reatores Biológicos
5.
J Toxicol Sci ; 48(1): 15-24, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36599424

RESUMO

We developed a derivatization technique that involves microwave heating to reduce the overall forensic analysis time of phosphorus-containing amino acid herbicides (PAAHs). Combined with an extraction method that uses titanium (IV) oxide (TiO2), we were able to obtain a practical analytical method for PAAHs and their metabolites in samples intended for poisoning cases. The optimized derivatization conditions were 700 W power and 5-min irradiation time, which is a significant time-saving. The plasma samples extracted using TiO2-packed Tip columns and derivatized under the optimized conditions had an intra-day accuracy and precision within 9.3% and 9.0%, respectively. The intermediate accuracy and precision were within 8.8% and 8.5%, respectively, and the recoveries were more than 91.2%. Similarly, for urine samples, the intra-day accuracy and precision were within 13.3% and 9.1%, respectively. The intermediate accuracy and precision were within 13.6% and 10.3%, respectively, and finally, the recoveries were more than 88.2%. In addition to reducing the pretreatment time, this method was suitable for reducing the overall labor burden on laboratories responsible for routine analysis because of its stable validation data.


Assuntos
Herbicidas , Aminoácidos , Fósforo , Micro-Ondas , Calefação
6.
Acta Crystallogr D Struct Biol ; 79(Pt 1): 31-39, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36601805

RESUMO

Proteins often assemble into functional complexes, the structures of which are more difficult to obtain than those of the individual protein molecules. Given the structures of the subunits, it is possible to predict plausible complex models via computational methods such as molecular docking. Assessing the quality of the predicted models is crucial to obtain correct complex structures. Here, an energy-scoring function was developed based on the interfacial residues of structures in the Protein Data Bank. The statistically derived energy function (Nepre) imitates the neighborhood preferences of amino acids, including the types and relative positions of neighboring residues. Based on the preference statistics, a program iNepre was implemented and its performance was evaluated with several benchmarking decoy data sets. The results show that iNepre scores are powerful in model ranking to select the best protein complex structures.


Assuntos
Aminoácidos , Proteínas , Aminoácidos/química , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/química , Termodinâmica , Conformação Proteica
7.
PLoS One ; 18(1): e0279931, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607993

RESUMO

BACKGROUND: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates. METHODOLOGY: DBS samples were collected within 48-72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed. RESULTS: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and 14.3% were preterm. Out of the total 610 neonates, 23.1% were small for GA. Reference intervals were generated for eleven amino acids, thirty-two acylcarnitines and succinylacetone concentrations. Markers were evaluated with respect to the influence of gender, GA, weight and time of sampling and statistically significant minimal differences were observed for some biomarkers. CONCLUSION: RI for amino acids, succinylacetone and acylcarnitine on DBS has been established for healthy neonates, which could be of use in the clinical practice. Clinically significant effect of GA, weight, gender and time of sampling on these markers were not identified.


Assuntos
Aminoácidos , Saúde do Lactente , Recém-Nascido , Feminino , Humanos , Lactente , Masculino , Carnitina , Recém-Nascido de Baixo Peso , Aminas
8.
Mol Cell ; 83(1): 57-73.e9, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36608670

RESUMO

The TFE3 and MITF master transcription factors maintain metabolic homeostasis by regulating lysosomal, melanocytic, and autophagy genes. Previous studies posited that their cytosolic retention by 14-3-3, mediated by the Rag GTPases-mTORC1, was key for suppressing transcriptional activity in the presence of nutrients. Here, we demonstrate using mammalian cells that regulated protein stability plays a fundamental role in their control. Amino acids promote the recruitment of TFE3 and MITF to the lysosomal surface via the Rag GTPases, activating an evolutionarily conserved phospho-degron and leading to ubiquitination by CUL1ß-TrCP and degradation. Elucidation of the minimal functional degron revealed a conserved alpha-helix required for interaction with RagA, illuminating the molecular basis for a severe neurodevelopmental syndrome caused by missense mutations in TFE3 within the RagA-TFE3 interface. Additionally, the phospho-degron is recurrently lost in TFE3 genomic translocations that cause kidney cancer. Therefore, two divergent pathologies converge on the loss of protein stability regulation by nutrients.


Assuntos
Aminoácidos , Fator de Transcrição Associado à Microftalmia , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Aminoácidos/metabolismo , Nutrientes , Estabilidade Proteica , Lisossomos/genética , Lisossomos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Mamíferos/metabolismo
9.
Arch Virol ; 168(2): 52, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609926

RESUMO

Bovine papillomaviruses (BPVs) exhibit a high degree of genetic variability, and several viral types have been identified based on analysis of the L1 gene. The L1 is the main capsid protein and the main target for neutralizing antibodies. We performed a retrospective study on BPVs circulating in Rio Grande do Sul state, Southern Brazil, in 2016-2020. DNA from 43 bovine papilloma samples were amplified using two degenerate primer sets - FAP59/64 and MY09/11 - targeting the L1 region, and analyzed for phylogeny, mixed BPV infections (coinfections) and amino acid (aa) sequences. We also performed an in silico analysis with 114 BPV L1 sequences from the GenBank database to assess the agreement between the phylogeny obtained based on complete L1 sequences versus that based on the region amplified using the FAP59/64 and MY09/11 primer sets. Considering single and coinfections, we identified 31 BPV-1 (31/43; 72.1%), 27 BPV-2 (27/43; 62.8%) and 4 BPV-6 (4/43; 9.3%). Coinfections with BPV-1 and BPV-2 were observed in 61.3% of the samples. Our results are supported by in silico analyses that demonstrate that the classification using FAP59/64 or MY09/11 matches the complete L1 results, except for BPV-17 and -18, which may be mistakenly classified depending on the primers used. Furthermore, we found unique or rare amino acids in at least one L1 sequence of each BPV type identified in our study, some of which have been identified previously in papillomavirus epitopes, suggesting immune-mediated selection. Finally, our study provides an overview of BPVs circulating in Southern Brazil over the last five years and point to the combined use of primers FAP59/64 and MY09/11 for analysis of BPV coinfections and putative epitopes.


Assuntos
Papillomavirus Bovino 1 , Doenças dos Bovinos , Coinfecção , Infecções por Papillomavirus , Animais , Bovinos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/veterinária , Filogenia , Brasil/epidemiologia , Aminoácidos/genética , Estudos Retrospectivos , DNA Viral/genética , Papillomaviridae/genética , Doenças dos Bovinos/epidemiologia
10.
J Chem Phys ; 158(1): 015102, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36610950

RESUMO

The ribosomal exit tunnel is the primary structure affecting the release of nascent proteins at the ribosome. The ribosomal exit tunnels from different species have elements of conservation and differentiation in structural and physico-chemical properties. In this study, by simulating the elongation and escape processes of nascent proteins at the ribosomal exit tunnels of four different organisms, we show that the escape process has conserved mechanisms across the domains of life. Specifically, it is found that the escape process of proteins follows the diffusion mechanism given by a simple diffusion model, and the median escape time positively correlates with the number of hydrophobic residues and the net charge of a protein for all the exit tunnels considered. These properties hold for 12 distinct proteins considered in two slightly different and improved Go-like models. It is also found that the differences in physico-chemical properties of the tunnels lead to quantitative differences in the protein escape times. In particular, the relatively strong hydrophobicity of E. coli's tunnel and the unusually high number of negatively charged amino acids on the tunnel's surface of H. marismortui lead to substantially slower escapes of proteins at these tunnels than at those of S. cerevisiae and H. sapiens.


Assuntos
Escherichia coli , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Escherichia coli/metabolismo , Ribossomos/química , Proteínas/química , Aminoácidos/química , Biossíntese de Proteínas
11.
Food Res Int ; 163: 112224, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596153

RESUMO

In this study, genomics and metabolomics were combined to reveal possible bio-synthetic pathways of core flavor compounds in pickled chayote via lactic acid bacteria (LAB) fermentation. The Lactiplantibacillus plantarum, Levilactobacillus brevis, and Lacticaseibacillus paracasei were selected as core LAB strains with better flavor-producing ability for chayote fermentation. The genomic results showed L. plantarum contained the largest number of metabolism annotated genes, while L. brevis had the fewest. Besides, the largest number of volatile compounds was detected in chayote fermented by L. plantarum, followed by L. brevis and L. paracasei. Some unique odor-active compounds (aldehydes, esters, and alcohols) and taste-active compounds (amino acids and dipeptides) were produced by different LAB strains. Accordingly, phenylalanine metabolic pathway (M00360), amino acid metabolic decomposition pathway (the Ehrlich pathway) and the anabolic pathway (the Harris pathway), and fatty acid biosynthesis pathway (M00061) were the main biosynthesis pathway involved in the flavor formation via LAB fermentation.


Assuntos
Lactobacillales , Lactobacillus plantarum , Lactobacillales/genética , Lactobacillus/metabolismo , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Álcoois/metabolismo , Aminoácidos/metabolismo , Genômica
12.
Food Res Int ; 163: 112257, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596168

RESUMO

Glyceryl core aldehyde (GCAs) are hazard factors produced during the frying process using oils and fats, and GCAs control and mitigation research is very important. This study investigated the effects of adding amino acids (methionine, glycine, and histidine) at 2.5, 5, and 10 mM on the formation and distribution of four GCAs during frying. High oleic sunflower oil (HOSO) was selected as frying oil for French fries. After 12 h of frying, the content of GCAs in the tert-butylhydroquinone-treated group (0.02 wt%, 1.1 mM) decreased by 29 % compared with the control group. The addition of methionine, glycine, and histidine decreased the total GCAs by 51 %, 28 %, and 27 %, respectively. The total GCAs content was best inhibited by methionine, while glycine and histidine were not significantly different from TBHQ. Methionine addition significantly reduced GCAs (9-oxo), GCAs (10-oxo-8), and GCAs (11-oxo-9) by 39 %, 78 %, and 80 %, respectively, while histidine was the most potent inhibitor of GCAs (8-oxo), which decreased by 40 %. Methionine also proved effective in slowing degradation of frying oil quality. These results provide a new direction for decreasing GCAs in frying systems.


Assuntos
Glicerol , Óleos Vegetais , Óleos Vegetais/química , Aminoácidos , Aldeídos/análise , Histidina , Culinária/métodos , Metionina , Glicina
13.
Food Res Int ; 163: 112256, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596167

RESUMO

Reducing sodium salt content in traditional fermented vegetables and developing low-salt fermented products have attracted increasing attention.However, low-salt fermented vegetables are prone to accumulate toxic biogenic amines (BAs) caused by the undesirable metabolism of spoilage microorganisms. This study aimed to investigate the impact of a CO2-modified atmosphere (MA) approach to the fermentation of low-salt Zhacai and the accumulation of BAs. The results show CO2-MA effectively suppressed the production of excessive BAs in low-salt Zhacai, as evidenced by a decrease in the total BA content from 63.66 to 161.41 mg/ kg under natural air conditions to 1.88-24.76 mg/ kg under CO2-MA. Overall, the mechanism of hindering BA formation was closely related to the change in the microbial community and the downregulation of BA-producing enzymes. Lactic acid bacteria, including Lactiplantibacillus plantarum, Weissella spp., and Pediococcus spp., were enriched under CO2-MA, whereas amine-producing microorganisms (e.g., Halomonas spp., Psychrobacter spp., Corynebacterium spp., and Levilactobacillus brevis) were greatly inhibited. Moreover, metagenomic analysis revealed that genes encoding amino acid decarboxylase, amine deiminase, and amine synthase were downregulated, which could be the fundamental reason for BA reduction. This study provides an alternative method for reducing BA production in fermented food.


Assuntos
Aminoácidos , Dióxido de Carbono , Fermentação , Aminoácidos/metabolismo , Aminas Biogênicas/análise , Verduras/metabolismo , Atmosfera
14.
World J Microbiol Biotechnol ; 39(3): 72, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625962

RESUMO

Protein hydrolysates are easily digested and utilized by humans and animals, and are less likely to cause allergies. Protein hydrolysis caused by endopeptidases often leads to the exposure of hydrophobic amino acids at the ends of peptides, which consequently causes bitter taste. Microbial aminopeptidases remove the exposed hydrophobic amino acids at the ends of aminopeptides, which improves taste, allowing for easier production. This processe is attacking significant attention from industry and laboratories. Aminopeptidases selectively hydrolyze peptide bonds from the N-terminal of proteins or peptides to produce free amino acids. Aminopeptidases can be classified into leucine, lysine, methionine and proline aminopeptidases by hydrolyzed N-terminal residues; metallo-, serine- and cysteine- aminopeptidases by the reaction mechanisms; dipeptide and triphoptide enzymes by the released number of amino acid residues at the end of hydrolyzed peptides; or acidic, neutral and basic aminopeptidases by their optimal hydrolysis pH. Commercial aminopeptidases are generally produced by microbial fermentation, and are mainly applied in the debittering of protein hydrolysates, the deep hydrolysis of protein, and the production of condiments, cheese, and bioactive peptides, as well as for disease detection in the medical industry.


Assuntos
Hidrolisados de Proteína , Paladar , Humanos , Animais , Hidrolisados de Proteína/química , Aminopeptidases/metabolismo , Peptídeos , Aminoácidos , Especificidade por Substrato
15.
Anal Chim Acta ; 1239: 340691, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628759

RESUMO

Bile acids (BAs) are a class of vital gut microbiota-host cometabolites, and they play an important role in maintaining gut microbiota-host metabolic homeostasis. Very recently, a new mechanism of BA anabolic metabolism mediated by gut microbiota (BA-amino acid conjugation) has been revealed, which provides a perspective for the research on BA metabolism and gut metabolome. In this study, we established a polarity-switching multiple reaction monitoring mass spectrometry-based screening method to mine amino acid-conjugated bile acids (AA-BAs) derived from host-gut microbiota co-metabolism. In addition, a retention time-based annotation strategy was further proposed to identify the AA-BA isomers and epimers. Using the developed methods, we successfully screened 118 AA-BA conjugates from mouse and human feces, 28 of them were confirmed by standards, and 62 putatively identified based on their predicted retention times. Moreover, we observed that the levels of most AA-BAs were significantly downregulated in the feces of chronic sleep deprivation mice, suggesting that the AA-BA metabolism was closely related to the physiological state of the host.


Assuntos
Aminoácidos , Ácidos e Sais Biliares , Camundongos , Humanos , Animais , Aminoácidos/análise , Cromatografia Líquida , Espectrometria de Massas , Ácidos e Sais Biliares/análise , Fezes/química
16.
Life Sci Alliance ; 6(3)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36631218

RESUMO

Growth differentiation factor 11 (GDF11) and GDF8 (MSTN) are closely related TGF-ß family proteins that interact with nearly identical signaling receptors and antagonists. However, GDF11 appears to activate SMAD2/3 more potently than GDF8 in vitro and in vivo. The ligands possess divergent structural properties, whereby substituting unique GDF11 amino acids into GDF8 enhanced the activity of the resulting chimeric GDF8. We investigated potentially distinct endogenous activities of GDF11 and GDF8 in vivo by genetically modifying their mature signaling domains. Full recoding of GDF8 to that of GDF11 yielded mice lacking GDF8, with GDF11 levels ∼50-fold higher than normal, and exhibiting modestly decreased muscle mass, with no apparent negative impacts on health or survival. Substitution of two specific amino acids in the fingertip region of GDF11 with the corresponding GDF8 residues resulted in prenatal axial skeletal transformations, consistent with Gdf11-deficient mice, without apparent perturbation of skeletal or cardiac muscle development or homeostasis. These experiments uncover distinctive features between the GDF11 and GDF8 mature domains in vivo and identify a specific requirement for GDF11 in early-stage skeletal development.


Assuntos
Aminoácidos , Miostatina , Feminino , Gravidez , Animais , Camundongos , Miostatina/genética , Miostatina/química , Aminoácidos/metabolismo , Fatores de Diferenciação de Crescimento/genética , Fatores de Diferenciação de Crescimento/química , Músculo Esquelético/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo
17.
ACS Appl Mater Interfaces ; 15(1): 651-661, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36591814

RESUMO

Phosphorene, also known as black phosphorus nanosheet (BPNS), has been investigated as a nanoagent for tumor therapy. However, promoting its intracellular accumulation while preventing the cytoplasmic decomposition remains challenging. Herein, for the first time, we propose a chiral BPNS designed through surface engineering based on amino acids with high biocompatibility and an abundant source for application in chirality-dependent tumor phototherapy based on its intracellular metabolism. The advantage of using cysteine (Cys) over other amino acids was that its d, l, or dl-form could efficiently work as the chirality inducer to modify the BPNS through electrostatic interaction and prevent alterations in the intrinsic properties of the BPNS. In particular, d-Cys-BPNS displayed an approximately threefold cytotoxic effect on tumor cells compared with l-Cys-BPNS, demonstrating a chirality-dependent therapy behavior. d-Cys-BPNS not only promoted high intracellular content but also showed resistance to cytoplasmic decomposition. Cys-engineered BPNS also demonstrated chirality-dependent phototherapy effects on tumor-bearing mice, in proximity to the results in vitro. Chiral engineering is expected to open new avenues that could promote the use of BPNS in tumor phototherapy and boost chiral nanomedicine.


Assuntos
Aminoácidos , Antineoplásicos , Camundongos , Animais , Aminoácidos/química , Cisteína/química , Fototerapia
18.
Anal Biochem ; 663: 115032, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36592921

RESUMO

Protein 3-hydroxyl-3-methylglutarylation (HMGylation) is newly discovered lysine acylation modification in mitochondrion. The accurate identification of HMGylation sites is the premise and key to further explore the molecular mechanisms of HMGylation. In this study, a novel bioinformatics tool named HMGPred is developed to predict HMGylation sites. Multiple effective features, including amino acid composition, amino acid factors, binary encoding, and the composition of k-spaced amino acid pairs, are integrated to encode HMGylation sites. And F-score feature ranking with incremental feature selection was used to eliminate redundant features. Moreover, a fuzzy support vector machine algorithm is used to effectively reduce the influence of noise problem by assigning different samples to different fuzzy membership degrees. As illustrated by 10-fold cross-validation, HMGPred achieves a satisfactory performance with an area under receiver operating characteristic curve of 0.9110. Feature analysis indicates that some k-spaced amino acid pair features, such as 'KxxxT' and 'DxxxE', play a critical role in the prediction of HMGylation sites. The results of prediction and analysis might be helpful for investigating the mechanisms of HMGylation. For the convenience of experimental researchers, HMGPred is implemented as a web server at http://123.206.31.171/HMGPred/.


Assuntos
Lisina , Máquina de Vetores de Suporte , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/química , Aminoácidos/metabolismo , Algoritmos , Biologia Computacional/métodos
19.
BMC Microbiol ; 23(1): 11, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36627553

RESUMO

BACKGROUND: Glutathione is an important bioactive tripeptide and is widely used in the food, medicine, and cosmetics industries. The aim of this study was to provide an efficient method for producing GSH and to explore its synthesis mechanism. Saccharomyces cerevisiae strain HBSD-W08 was screened for GSH production, and its fermentation medium was optimized using single-factor experiments of the Plackett-Burman and central composite rotatable designs. This method was used to analyze the effects of the presence and concentration of various carbon sources, organic and inorganic nitrogen sources, metal ions, and precursor amino acids on GSH production and catalase, superoxide dismutase, and γ-glutamylcysteine synthetase activity. RESULTS: The three most significant factors affecting GSH production were peptone (optimal concentration [OC]: 2.50 g L- 1), KH2PO4 (OC: 0.13 g L- 1), and glutamic acid (OC: 0.10 g L- 1). GSH productivity of HBSD-W08 was obtained at 3.70 g L- 1 in the optimized medium. The activity of γ-GCS, which is a marker for oxidative stress, was found to be highly positively correlated with GSH production. CONCLUSIONS: This finding revealed an underlying relationship between GSH synthesis and oxidative stress, providing useful information for developing effective GSH fermentation control strategies.


Assuntos
Glutationa , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Fermentação , Meios de Cultura/metabolismo , Glutationa/metabolismo , Aminoácidos/metabolismo
20.
Int J Mol Sci ; 24(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36614247

RESUMO

The relative contribution of mutation and selection to the amino acid substitution rates observed in empirical matrices is unclear. Herein, we present a neutral continuous fitness-stability model, inspired by the Arrhenius law (qij=aije-ΔΔGij). The model postulates that the rate of amino acid substitution (i→j) is determined by the product of a pre-exponential factor, which is influenced by the genetic code structure, and an exponential term reflecting the relative fitness of the amino acid substitutions. To assess the validity of our model, we computed changes in stability of 14,094 proteins, for which 137,073,638 in silico mutants were analyzed. These site-specific data were summarized into a 20 square matrix, whose entries, ΔΔGij, were obtained after averaging through all the sites in all the proteins. We found a significant positive correlation between these energy values and the disease-causing potential of each substitution, suggesting that the exponential term accurately summarizes the fitness effect. A remarkable observation was that amino acids that were highly destabilizing when acting as the source, tended to have little effect when acting as the destination, and vice versa (source → destination). The Arrhenius model accurately reproduced the pattern of substitution rates collected in the empirical matrices, suggesting a relevant role for the genetic code structure and a tuning role for purifying selection exerted via protein stability.


Assuntos
Evolução Molecular , Proteoma , Proteoma/genética , Substituição de Aminoácidos , Modelos Genéticos , Aminoácidos/genética , Aminoácidos/química
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