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1.
J R Soc Interface ; 21(214): 20240014, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715323

RESUMO

Prebiotic peptide synthesis has consistently been a prominent topic within the field of the origin of life. While research predominantly centres on the 20 classical amino acids, the synthesis process encounters significant thermodynamic barriers. Consequently, amino acid analogues are being explored as potential building blocks for prebiotic peptide synthesis. This review delves into the pathway of polypeptide formation, identifying specific amino acid analogues that might have existed on early Earth, potentially participating in peptide synthesis and chemical evolution. Moreover, considering the complexity and variability of the environment on early Earth, we propose the plausibility of coevolution between amino acids and their analogues.


Assuntos
Aminoácidos , Evolução Química , Peptídeos , Aminoácidos/química , Peptídeos/química , Origem da Vida , Prebióticos
2.
Molecules ; 29(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731439

RESUMO

The production of peanut oil in the industrial sector necessitates the utilization of diverse raw materials to generate consistent batches with stable flavor profiles, thereby leading to an increased focus on understanding the correlation between raw materials and flavor characteristics. In this study, sensory evaluations, headspace solid-phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC-MS), odor activity value (OAV) calculations, and correlation analysis were employed to investigate the flavors and main contributing amino acids of hot-pressed oils derived from different peanut varieties. The results confirmed that the levels of alcohols, aldehydes, and heterocyclic compounds in peanut oil varied among nine different peanut varieties under identical processing conditions. The OAVs of 25 key aroma compounds, such as methylthiol, 3-ethyl-2,5-dimethylpyrazine, and 2,3-glutarone, exceeded a value of 1. The sensory evaluations and flavor content analysis demonstrated that pyrazines significantly influenced the flavor profile of the peanut oil. The concentrations of 11 amino acids showed a strong correlation with the levels of pyrazines. Notably, phenylalanine, lysine, glutamic acid, arginine, and isoleucine demonstrated significant associations with both pyrazine and nut flavors. These findings will provide valuable insights for enhancing the sensory attributes of peanut oil and selecting optimal raw peanuts for its production.


Assuntos
Aminoácidos , Arachis , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Óleo de Amendoim , Aminoácidos/análise , Aminoácidos/química , Arachis/química , Odorantes/análise , Óleo de Amendoim/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Aromatizantes/química , Aromatizantes/análise , Pirazinas/química , Pirazinas/análise , Microextração em Fase Sólida , Paladar , Temperatura Alta
3.
Molecules ; 29(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38731521

RESUMO

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.


Assuntos
Domínio Catalítico , Inibidores Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Aminoácidos/química , Aminoácidos/metabolismo , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/química , Lactato Desidrogenase 5/metabolismo , Lactato Desidrogenase 5/antagonistas & inibidores , Lactato Desidrogenase 5/química , Ácido Pirúvico/metabolismo , Ácido Pirúvico/química , Mutagênese Sítio-Dirigida , Simulação de Dinâmica Molecular
4.
J Med Life ; 17(1): 24-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38737662

RESUMO

Neurological disorders, ranging from acute forms such as stroke and traumatic brain injury to neurodegenerative diseases like dementia, are the leading cause of disability-adjusted life years (DALYs) worldwide. A promising approach to address these conditions and promote nervous system regeneration is the use of the neuropeptide preparation Cerebrolysin, which has been shown to be effective in both clinical and preclinical studies. Despite claims of similar clinical efficacy and safety by several peptide preparations, concerns regarding their generic composition and efficacy have been previously raised. Based on these reports, we analyzed the peptide composition and neurotrophic activity of several peptide preparations allegedly similar to Cerebrolysin and approved in some countries for treating neurological diseases. Our results demonstrate that these preparations lack relevant biological activity and that the peptide composition is significantly different from Cerebrolysin. peptide.


Assuntos
Aminoácidos , Peptídeos , Aminoácidos/farmacologia , Humanos , Peptídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais
5.
Int J Biol Sci ; 20(7): 2779-2789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725849

RESUMO

Selenium (Se) is an essential trace element for biological processes. Seleno-amino acids (Se-AAs), known as the organic forms of Se, and their metabolic reprogramming have been increasingly recognized to regulate antioxidant defense, enzyme activity, and tumorigenesis. Therefore, there is emerging interest in exploring the potential application of Se-AAs in antitumor therapy. In addition to playing a vital role in inhibiting tumor growth, accumulating evidence has revealed that Se-AA metabolism could reshape the tumor microenvironment (TME) and enhance immunotherapy responses. This review presents a comprehensive overview of the current progress in multifunctional Se-AAs for antitumor treatment, with a particular emphasis on elucidating the crosstalk between Se-AA metabolism and various cell types in the TME, including tumor cells, T cells, macrophages, and natural killer cells. Furthermore, novel applications integrating Se-AAs are also discussed alongside prospects to provide new insights into this emerging field.


Assuntos
Aminoácidos , Imunoterapia , Neoplasias , Selênio , Microambiente Tumoral , Humanos , Imunoterapia/métodos , Aminoácidos/metabolismo , Selênio/uso terapêutico , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/imunologia
6.
Food Res Int ; 186: 114306, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729707

RESUMO

The aim of this research was to find out the effect of different combinations of starter and non-starter cultures on the proteolysis of Castellano cheese during ripening. Four cheese batches were prepared, each containing autochthonous lactobacilli and or Leuconostoc, and were compared with each other and with a control batch, that used only a commercial starter. To achieve this, nitrogen fractions (pH 4.4-soluble nitrogen and 12 % trichloroacetic acid soluble nitrogen, polypeptide nitrogen and casein nitrogen), levels of free amino acids and biogenic amines were assessed. Texture and microstructure of cheeses were also evaluated. Significant differences in nitrogen fractions were observed between batches at different stages of ripening. The free amino acid content increased throughout the cheese ripening process, with a more significant increase occurring after the first 30 days. Cheeses containing non-starter lactic acid bacteria exhibited the highest values at the end of the ripening period. Among the main amino acids, GABA was particularly abundant, especially in three of the cheese batches at the end of ripening. The autochthonous lactic acid bacteria were previously selected as non-producers of biogenic amines and this resulted in the absence of these compounds in the cheeses. Analysis of the microstructure of the cheese reflected the impact of proteolysis. Additionally, the texture profile analysis demonstrated that the cheese's hardness intensified as the ripening period progressed. The inclusion of autochthonous non-starter lactic acid bacteria in Castellano cheese production accelerated the proteolysis process, increasing significantly the free amino acids levels and improving the sensory quality of the cheeses.


Assuntos
Aminoácidos , Aminas Biogênicas , Queijo , Proteólise , Queijo/microbiologia , Queijo/análise , Aminoácidos/análise , Aminoácidos/metabolismo , Aminas Biogênicas/análise , Microbiologia de Alimentos , Manipulação de Alimentos/métodos , Leuconostoc/metabolismo , Leuconostoc/crescimento & desenvolvimento , Lactobacillus/metabolismo , Lactobacillus/crescimento & desenvolvimento , Nitrogênio/análise , Qualidade dos Alimentos , Fermentação
7.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732146

RESUMO

The ubiquitin-proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work. Following a recent study by Ciechanover's group showing that amino acid (AA) starvation in cultured cancer cell lines modulates proteasome intracellular localization and activity, we tested two hypotheses in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs, CMs): (i) AA starvation causes proteasome translocation in CMs, similarly to the observation in cultured cancer cell lines; (ii) manipulation of subcellular proteasomal compartmentalization is associated with electrophysiological abnormalities in the form of arrhythmias, mediated via altered intracellular Ca2+ handling. The major findings are: (i) starving CMs to AAs results in proteasome translocation from the nucleus to the cytoplasm, while supplementation with the aromatic amino acids tyrosine (Y), tryptophan (W) and phenylalanine (F) (YWF) inhibits the proteasome recruitment; (ii) AA-deficient treatments cause arrhythmias; (iii) the arrhythmias observed upon nuclear proteasome sequestration(-AA+YWF) are blocked by KB-R7943, an inhibitor of the reverse mode of the sodium-calcium exchanger NCX; (iv) the retrograde perfusion of isolated rat hearts with AA starvation media is associated with arrhythmias. Collectively, our novel findings describe a newly identified mechanism linking the UPS to arrhythmia generation in CMs and whole hearts.


Assuntos
Arritmias Cardíacas , Cálcio , Miócitos Cardíacos , Complexo de Endopeptidases do Proteassoma , Miócitos Cardíacos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Humanos , Cálcio/metabolismo , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/etiologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Estresse Fisiológico , Transporte Proteico , Ratos , Aminoácidos/metabolismo
8.
Ulus Travma Acil Cerrahi Derg ; 30(5): 323-327, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738676

RESUMO

BACKGROUND: We investigated the utility of specific biomarkers-namely, c-terminal telopeptide (CTX), n-telopeptide (NTX), deoxypyridinoline (DPD), and tartrate-resistant acid phosphatase (TRAP)-compared to conventional diagnostic methods. We hy-pothesized that these novel biomarkers could hold substantial value in the diagnosis, treatment, and monitoring of osteoporosis. METHODS: The study was conducted over a three-year period, from January 1, 2020, to January 1, 2023. We enrolled a total of 520 patients aged 50 years or older who had been diagnosed with osteoporosis. Patients undergoing steroid treatments, which are known to contribute to osteoporosis, were excluded from the study. Additionally, we carefully selected and matched a control group consisting of 500 patients based on demographic characteristics relevant to the diagnosis of osteoporosis. This meticulous selection process resulted in a comprehensive cohort comprising 1,020 patients. Throughout the study, patients were closely monitored for a duration of one year to track the occurrence of pathological fractures and assess their overall prognosis. RESULTS: As a result of our rigorous investigation, we identified CTX, NTX, DPD, and TRAP as pivotal biomarkers that play a crucial role in evaluating bone health, monitoring treatment effectiveness, and detecting pathological fractures in the context of osteoporosis. CONCLUSION: Our study underscores the significance of these biomarkers in advancing the diagnosis and management of osteo-porosis, offering valuable insights into the disease's progression and treatment outcomes.


Assuntos
Biomarcadores , Remodelação Óssea , Colágeno Tipo I , Osteoporose , Humanos , Biomarcadores/sangue , Feminino , Osteoporose/diagnóstico , Masculino , Pessoa de Meia-Idade , Idoso , Colágeno Tipo I/sangue , Peptídeos/sangue , Peptídeos/urina , Fosfatase Ácida Resistente a Tartarato/sangue , Aminoácidos/sangue , Fraturas por Osteoporose/diagnóstico , Fraturas Espontâneas/diagnóstico , Fraturas Espontâneas/etiologia
9.
Cell Mol Life Sci ; 81(1): 217, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748186

RESUMO

The vertebrate sense of taste allows rapid assessment of the nutritional quality and potential presence of harmful substances prior to ingestion. Among the five basic taste qualities, salty, sour, sweet, umami, and bitter, bitterness is associated with the presence of putative toxic substances and elicits rejection behaviors in a wide range of animals including humans. However, not all bitter substances are harmful, some are thought to be health-beneficial and nutritious. Among those compound classes that elicit a bitter taste although being non-toxic and partly even essential for humans are bitter peptides and L-amino acids. Using functional heterologous expression assays, we observed that the 5 dominant human bitter taste receptors responsive to bitter peptides and amino acids are activated by bile acids, which are notorious for their extreme bitterness. We further demonstrate that the cross-reactivity of bitter taste receptors for these two different compound classes is evolutionary conserved and can be traced back to the amphibian lineage. Moreover, we show that the cross-detection by some receptors relies on "structural mimicry" between the very bitter peptide L-Trp-Trp-Trp and bile acids, whereas other receptors exhibit a phylogenetic conservation of this trait. As some bile acid-sensitive bitter taste receptor genes fulfill dual-roles in gustatory and non-gustatory systems, we suggest that the phylogenetic conservation of the rather surprising cross-detection of the two substance classes could rely on a gene-sharing-like mechanism in which the non-gustatory function accounts for the bitter taste response to amino acids and peptides.


Assuntos
Ácidos e Sais Biliares , Peptídeos , Receptores Acoplados a Proteínas G , Paladar , Ácidos e Sais Biliares/metabolismo , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Animais , Paladar/fisiologia , Peptídeos/metabolismo , Filogenia , Células HEK293 , Aminoácidos/metabolismo , Membrana Celular/metabolismo
10.
Sci Rep ; 14(1): 10388, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710760

RESUMO

Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020. The dynamics of multiple laboratory parameters (including inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and parameters of iron and vitamin B metabolism) was related to disease severity and patients' physical performance. Also, symptom load during acute illness and at approximately 60 days (FU1), and one year after symptom onset (FU2) were monitored and related with changes of the investigated laboratory parameters: During acute infection many investigated laboratory parameters were elevated (e.g., inflammatory markers, ferritin, kynurenine, phenylalanine) and enhanced tryptophan catabolism and phenylalanine accumulation were found. At FU2 nearly all laboratory markers had declined back to reference ranges. However, kynurenine/tryptophan ratio (Kyn/Trp) and the phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 95th percentile of healthy controls in about two thirds of our cohort at FU2. Lower tryptophan concentrations were associated with B vitamin availability (during acute infection and at FU1), patients with lower vitamin B12 levels at FU1 had a prolonged and more severe impairment of their physical functioning ability. Patients who had fully recovered (ECOG 0) presented with higher concentrations of iron parameters (ferritin, hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) at FU2 compared to patients with restricted ability to work. Persistent symptoms at FU2 were tendentially associated with IFN-γ related parameters. Women were affected by long-term symptoms more frequently. Conclusively, inflammation-mediated biochemical changes appear to be related to symptoms of patients with acute and Long Covid.


Assuntos
Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/sangue , COVID-19/complicações , COVID-19/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , SARS-CoV-2/isolamento & purificação , Idoso , Adulto , Desempenho Físico Funcional , Interleucina-6/sangue , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Inflamação , Triptofano/sangue , Triptofano/metabolismo , Neopterina/sangue , Fenilalanina/sangue , Fenilalanina/metabolismo , Aminoácidos/sangue
11.
J Drugs Dermatol ; 23(5): 366-375, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709706

RESUMO

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.


Assuntos
Fibroblastos , Proteínas Filagrinas , Metaloproteinase 1 da Matriz , Fator 2 Relacionado a NF-E2 , Fator de Necrose Tumoral alfa , Raios Ultravioleta , Humanos , Raios Ultravioleta/efeitos adversos , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Fibroblastos/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Protetores Solares/administração & dosagem , Protetores Solares/química , Protetores Solares/farmacologia , Aminoácidos/administração & dosagem , Aminoácidos/farmacologia , Aminoácidos/química , Interleucina-1alfa/metabolismo , Histamina/sangue , Creme para a Pele/administração & dosagem , Biomarcadores/metabolismo , Colágeno Tipo I , Proteínas de Filamentos Intermediários/metabolismo , Antígeno Ki-67/metabolismo , Dímeros de Pirimidina , Células Cultivadas
12.
BMC Cancer ; 24(1): 555, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702616

RESUMO

Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted.In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS.Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30-0.83, P < 0.01).Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively.


Assuntos
Aminoácidos , Biomarcadores Tumorais , Humanos , Masculino , Feminino , Aminoácidos/sangue , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/sangue , Ampola Hepatopancreática/patologia , Espectrometria de Massas em Tandem , Diagnóstico Diferencial , Neoplasias do Ducto Colédoco/sangue , Neoplasias do Ducto Colédoco/diagnóstico , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/sangue , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Adulto , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Cromatografia Líquida , Análise de Componente Principal , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia
13.
Food Res Int ; 183: 114231, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38760148

RESUMO

This research assessed how three preprocessing techniques [soaking (S), soaking and reconstitution (SR), and soaking and dehulling (SD)] impact the protein digestibility and bioactivity of faba bean flours when combined with thermoplastic extrusion. Samples were compared against a control (C) of extruded faba bean flour without preprocessing. Applying preprocessing techniques followed by extrusion diminished antinutrient levels while enhancing protein hydrolysis and in vitro bioactivity in higher extent compared to C. Specifically, SD combined with extrusion was the most effective, achieving an 80% rate of protein hydrolysis and uniquely promoting the release of gastric digestion-resistant proteins (50-70 kDa). It also resulted in the highest release of small peptides (<3kDa, 22.51%) and free amino acids (15.50%) during intestinal digestion. Moreover, while all preprocessing techniques increased antioxidant (ABTS radical-scavenging), antidiabetic, and anti-hypertensive activities, SD extruded flour displayed the highest levels of dipeptidyl peptidase inhibition (DPP-IVi, IC50=13.20 µg/mL), pancreatic α-amylase inhibition (IC50=8.59 mg/mL), and angiotensin I-converting enzyme inhibition (ACEi, IC50=1.71 mg protein/mL). As a result, it was selected for further peptide and in silico bioactive analysis. A total of 24 bioactive peptides were identified in intestinal digests from SD extruded flour, all with potential DPP-IVi and ACEi activities, and six were also predicted as antioxidant peptides. VIPAGYPVAIK and GLTETWNPNHPEL were highlighted as resistant bioactive peptides with the highest antidiabetic and antioxidant potential. Our findings demonstrated that combining preprocessing (particularly SD) and thermoplastic extrusion enhances protein digestibility in faba beans and promotes the release of beneficial bioactive peptides in the intestine.


Assuntos
Digestão , Farinha , Manipulação de Alimentos , Peptídeos , Vicia faba , Vicia faba/química , Farinha/análise , Manipulação de Alimentos/métodos , Antioxidantes/análise , Valor Nutritivo , Hidrólise , Aminoácidos/análise , Aminoácidos/metabolismo , Proteínas de Plantas/metabolismo
14.
Commun Biol ; 7(1): 586, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755285

RESUMO

Bats serve as reservoirs for numerous zoonotic viruses, yet they typically remain asymptomatic owing to their unique immune system. Of particular significance is the MHC-I in bats, which plays crucial role in anti-viral response and exhibits polymorphic amino acid (AA) insertions. This study demonstrated that both 5AA and 3AA insertions enhance the thermal stability of the bat MHC-I complex and enrich the diversity of bound peptides in terms of quantity and length distribution, by stabilizing the 310 helix, a region prone to conformational changes during peptide loading. However, the mismatched insertion could diminish the stability of bat pMHC-I. We proposed that a suitable insertion may help bat MHC-I adapt to high body temperatures during flight while enhancing antiviral responses. Moreover, this site-specific insertions may represent a strategy of evolutionary adaptation of MHC-I molecules to fluctuations in body temperature, as similar insertions have been found in other lower vertebrates.


Assuntos
Quirópteros , Antígenos de Histocompatibilidade Classe I , Animais , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Estabilidade Proteica , Peptídeos/química , Peptídeos/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Apresentação de Antígeno , Mutagênese Insercional
15.
Nat Commun ; 15(1): 3708, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714662

RESUMO

Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H2 is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H2O as the sole byproduct.


Assuntos
Aminoácidos , Compostos de Anilina , Boranos , Peptídeos , Compostos de Anilina/química , Catálise , Aminoácidos/química , Peptídeos/química , Boranos/química , Hidrogênio/química , Simulação por Computador , Oxirredução , Alquilação , Aprendizado de Máquina
16.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732028

RESUMO

The development of turn-based inhibitors of protein-protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR, NMR, CD) have shown that, for peptides, the backbone chirality and bulkiness of the amino acid side chains determine the hydrogen-bond pattern, allowing tuning of the size of the preferred hydrogen-bonded ring in turn-folded structures. However, their biological potential is more dependent on their lipophilicity. In addition, our pioneering work on the chiroptical properties of aminoferrocene-containing peptides enables the correlation of their geometry with the sign of the CD signal in the absorption region of the ferrocene chromophore. These studies have opened up the possibility of using aminoferrocene and its derivatives as chirooptical probes for the determination of various chirality elements, such as the central chirality of amino acids and the helicity of peptide sequences.


Assuntos
Aminoácidos , Compostos Ferrosos , Metalocenos , Peptídeos , Compostos Ferrosos/química , Aminoácidos/química , Metalocenos/química , Peptídeos/química , Ligação de Hidrogênio , Estereoisomerismo
17.
Biointerphases ; 19(2)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38602440

RESUMO

In mass spectrometry imaging (MSI), ion suppression can lead to a misinterpretation of results. Particularly phospholipids, most of which exhibit high gas-phase basicity (GB), are known to suppress the detection of metabolites and drugs. This study was initiated by the observation that the signal of an herbicide, i.e., atrazine, was suppressed in MSI investigations of earthworm tissue sections. Herbicide accumulation in earthworms was investigated by time-of-flight secondary ion mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Additionally, earthworm tissue sections without accumulation of atrazine but with a homogeneous spray deposition of the herbicide were analyzed to highlight region-specific ion suppression. Furthermore, the relationship of signal intensity and GB in binary mixtures of lipids, amino acids, and atrazine was investigated in both MSI techniques. The GB of atrazine was determined experimentally through a linear plot of the obtained intensity ratios of the binary amino acid mixtures, as well as theoretically. The GBs values for atrazine of 896 and 906 kJ/mol in ToF-SIMS and 933 and 987 kJ/mol in MALDI-MSI were determined experimentally and that of 913 kJ/mol by quantum mechanical calculations. Compared with the GB of a major lipid component, phosphatidylcholine (GBPC = 1044.7 kJ/mol), atrazine's experimentally and computationally determined GBs in this work are significantly lower, making it prone to ion suppression in biological samples containing polar lipids.


Assuntos
Atrazina , Herbicidas , Oligoquetos , Animais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Aminoácidos , Fosfatidilcolinas , Lasers
18.
Luminescence ; 39(4): e4740, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38618664

RESUMO

A lanthanide complex based on europium (Eu) and chelidamic acid was synthesized (Eu-CHE) and characterized. The complex Eu-CHE exhibited intense luminescence at 615 nm under excitation at 300 nm and was further investigated for highly sensitive turn-off detection of l-kynurenine (l-kyn), a cancer biomarker. The probe detected l-kyn linearly from 6 nM to 0.2 µM with a limit of detection and limit of quantification of 1.37 and 4.57 nM, respectively. The probe was investigated for selectivity towards l-kyn among co-existing amino acids and further extended for detecting l-kyn from human serum and urine samples. A low-cost paper strip-based sensing platform was also developed for the visual detection of l-kyn.


Assuntos
Elementos da Série dos Lantanídeos , Neoplasias , Humanos , Cinurenina , Biomarcadores Tumorais , Neoplasias/diagnóstico , Aminoácidos , Európio
19.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38622951

RESUMO

We determined apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of crude protein (CP) and amino acids (AA) in fermented soybean meal from five different sources (FSBM 1 to 5) in China when fed to mid and late-gestating sows. Twenty-four parity four sows (12 at 30 d in gestation and 12 at 80 d in gestation) were fitted with a T-cannula in the distal ileum and used in this experiment. Sows were randomly assigned to a replicated 6 × 3 Youden square design including six diets and three periods. Six diets were provided for sows in mid and late gestation, including a nitrogen-free diet and five test diets containing 26% FSBM from different sources. Results showed that there were differences in AID and SID of CP among the different FSBM samples, but no differences between sow physiological stages were observed. Specifically, when mid-gestating sows were fed FSBM 2, the AID of CP was the lowest, whereas FSBM 3 exhibited a greater AID of CP when compared to the other FSBM samples (P < 0.01). Furthermore, during late gestation, FSBM 3 consistently had greater SID of CP when compared to other FSBM samples (P < 0.01). The ileal digestibility of most AA varied with different FSBM samples. In both mid and late gestation, differences (P < 0.05) were observed for AID of lysine, tryptophan, histidine, and arginine across different FSBM samples. Similarly, the AID of dispensable AA (cysteine, glutamine, and serine) also exhibited differences (P < 0.05) across different FSBM samples in both mid and late-gestating sows. For mid-gestating sows, SID differences relating to lysine, phenylalanine, tryptophan, threonine, and arginine were observed among different diets (P < 0.05). In late-gestating sows, SID values for lysine, tryptophan, leucine, and arginine differed across diets (P < 0.05). Furthermore, the ileal digestibility of some dispensable AA was influenced by physiological stage, as evidenced by greater AID and SID values for glycine, glutamine, cysteine, and serine in late-gestating sows when compared to mid-gestating sows (P < 0.01). In summary, our study determined AA ileal digestibility of different FSBM fed to mid and late-gestating sows. We observed that the AA ileal digestibility differed among five FSBM samples, but the physiological stage of sows did not affect the ileal digestibility of CP and most AA. Additionally, when formulating diets for sows, it is crucial to consider the nutritional value differences of FSBM.


Fermented soybean meal (FSBM) is obtained from the microbial fermentation of soybean meal, which reduces anti-nutritional factor levels and enhances other nutrient content. Substituting soybean meal with FSBM in piglet and growing pig diets improves nutrient digestibility. However, its nutritional value for sows remains unclear. Therefore, five sources of FSBM were fed to sows in mid and late gestation to evaluate apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of amino acids (AA). We found that different FSBM samples impacted the SID value of AA when fed to gestating sows. Additionally, sow physiological stage influenced the SID of some dispensable AA. These findings provide valuable insights into the incorporation of FSBM into sow diets.


Assuntos
Aminoácidos , Alimentos Fermentados , Suínos , Animais , Feminino , Gravidez , Aminoácidos/metabolismo , Digestão/fisiologia , Glutamina/metabolismo , Triptofano/metabolismo , Cisteína/metabolismo , Lisina/metabolismo , Glycine max , Dieta/veterinária , Arginina/metabolismo , Serina , Ração Animal/análise , Íleo/metabolismo , Fenômenos Fisiológicos da Nutrição Animal
20.
Adv Exp Med Biol ; 1446: 135-154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625527

RESUMO

The hair and skin of domestic cats or dogs account for 2% and 12-24% of their body weight, respectively, depending on breed and age. These connective tissues contain protein as the major constituent and provide the first line of defense against external pathogens and toxins. Maintenance of the skin and hair in smooth and elastic states requires special nutritional support, particularly an adequate provision of amino acids (AAs). Keratin (rich in cysteine, serine and glycine) is the major protein both in the epidermis of the skin and in the hair. Filaggrin [rich in some AAs (e.g., serine, glutamate, glutamine, glycine, arginine, and histidine)] is another physiologically important protein in the epidermis of the skin. Collagen and elastin (rich in glycine and proline plus 4-hydroxyproline) are the predominant proteins in the dermis and hypodermis of the skin. Taurine and 4-hydroxyproline are abundant free AAs in the skin of dogs and cats, and 4-hydroxyproline is also an abundant free AA in their hair. The epidermis of the skin synthesizes melanin (the pigment in the skin and hair) from tyrosine and produces trans-urocanate from histidine. Qualitative requirements for proteinogenic AAs are similar between cats and dogs but not identical. Both animal species require the same AAs to nourish the hair and skin but the amounts differ. Other factors (e.g., breeds, coat color, and age) may affect the requirements of cats or dogs for nutrients. The development of a healthy coat, especially a black coat, as well as healthy skin critically depends on AAs [particularly arginine, glycine, histidine, proline, 4-hydroxyproline, and serine, sulfur AAs (methionine, cysteine, and taurine), phenylalanine, and tyrosine] and creatine. Although there are a myriad of studies on AA nutrition in cats and dogs, there is still much to learn about how each AA affects the growth, development and maintenance of the hair and skin. Animal-sourced foodstuffs (e.g., feather meal and poultry by-product meal) are excellent sources of the AAs that are crucial to maintain the normal structure and health of the skin and hair in dogs and cats.


Assuntos
Doenças do Gato , Doenças do Cão , Gatos , Cães , Animais , Aminoácidos , Histidina , Cisteína , Hidroxiprolina , Cabelo , Glicina , Tirosina , Taurina , Serina , Prolina , Arginina
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