RESUMO
COVID-19 disease, triggered by SARS-CoV-2 virus infection, has led to more than 7.0 million deaths worldwide, with a significant fraction of recovered infected people reporting postviral symptoms. Smart surfaces functionalized with nanoparticles are a powerful tool to inactivate the virus and prevent the further spreading of the disease. Literature reports usually focus on the role of nanomaterial composition and size dispersion in evaluating their efficacy against SARS-CoV-2. Here, the anti-SARS-CoV-2 activity of oleylamine (OAm) used as a capping agent of silver nanoparticles is quantified for the first time. Spherical hydrophobic nanoparticles with 8 ± 2 nm diameter were prepared and characterized by Fourier transform infrared, dynamic light scattering, and transmission electron microscopy techniques. Biological assays showed that microgram amounts of nanoparticles, deposited on nonwoven textile obtained from surgical masks, efficiently inactivated up to 99.6(2)% of the virus with just 2 min of exposure. The virucidal activity of the corresponding amount of free OAm has been determined as well, reaching up to 67(1)% of activity for an exposure time of 10 min. Inductively coupled plasma optical emission spectrometry results pointed out a low leaching out of the nanoparticles in contact with water or culture medium. All in all, these results propose the capping molecules as an important chemical variable to be taken into account in the design of fast, efficient, and long-lasting anti-SARS-CoV-2 coatings.
Assuntos
Aminas , Antivirais , COVID-19 , Nanopartículas Metálicas , SARS-CoV-2 , Prata , Têxteis , Prata/química , Prata/farmacologia , SARS-CoV-2/efeitos dos fármacos , Nanopartículas Metálicas/química , Antivirais/farmacologia , Antivirais/química , Aminas/química , Aminas/farmacologia , COVID-19/virologia , Humanos , Chlorocebus aethiops , Células Vero , AnimaisRESUMO
This study synergizes machine learning (ML) with conceptual density functional theory (CDFT) to develop OECD-compliant predictive models for the mutagenic activity of aromatic amines (AAs) with a fully No-Code methodology using a comprehensive data set of 251 AAs, Leave-One-Out-Cross-Validation (LOOCV), and three distinct data splits. Our research employs the GFN2-xTB method, known for its robustness and speed, to compute descriptors for procarcinogens and their activated metabolites in vacuum and aqueous phases. We evaluate the effectiveness of different theoretical definitions of electrophilicity within CDFT, namely, PSL, GCV, and CDP schemes, and the newly introduced Log QP descriptor to approximate Log P information. SPAARC, RandomTree, and JCHAID* ML methods were used to build explainable predictive models with highly robust internal validation (Avg. Correct Classifications = 76% and Avg. Kappa = 0.29) and external validation (Avg. Correct Classifications = 79% and Avg. Kappa = 0.33) metrics, and the results were compared to those of a two hidden layer Multilayer Perceptron. The results indicate that the second CDP definition for the electrophilicity in both vacuum and aqueous phases and also the newly presented Log QP descriptors are the most important ones for predicting the mutagenic activity of AA (namely ω+VacCDP2+, ω+AqCDP2+, and LogQP1+Vac, respectively). The results indicate that metabolic activation, aqueous solvent properties, and the CDP electrophilicity schemes and Log QP should be considered when building predictive models for the mutagenic activity of AA. This study offers a replicable, No-Code approach to QSAR research, making high-level ML and CDFT applications accessible to a broader audience. Future work will expand these methods to other compound families, enhancing predictive capabilities in the study of mutagenic activities and other biological phenomena.
Assuntos
Aminas , Teoria da Densidade Funcional , Aprendizado de Máquina , Mutagênicos , Aminas/química , Aminas/toxicidade , Mutagênicos/toxicidade , Mutagênicos/química , Relação Quantitativa Estrutura-AtividadeRESUMO
Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.
Assuntos
Aminas , Cucumis sativus , Germinação , Ferro , Microgéis , Sementes , Germinação/efeitos dos fármacos , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/química , Ferro/metabolismo , Ferro/química , Aminas/química , Aminas/metabolismo , Microgéis/química , Compostos de Epóxi/química , Compostos de Epóxi/metabolismo , Peixe-Zebra/metabolismo , AnimaisRESUMO
A number of different approaches have been used for quantitative peptidomics. In this protocol, we describe the method in which peptides are reacted with formaldehyde and sodium cyanoborohydride, which converts primary and secondary amines into tertiary amines. By using different combinations of regular reagents, deuterated reagents (2H), and reagents containing deuterium and 13C, it is possible to produce five isotopically distinct forms of the methylated peptides, which can be quantified by mass spectrometry. Peptides with free N-termini that are primary amines incorporate two methyl groups using this procedure, which differ by 2 Da for each of the five isotopic combinations. Peptides that contain unmodified lysine residues incorporate additional pairs of methyl groups, leading to larger mass differences between isotopic forms. The reagents are commercially available, relatively inexpensive, and chemically stable.
Assuntos
Aminas , Peptídeos , Peptídeos/química , Espectrometria de Massas/métodos , Metilação , Proteômica/métodosRESUMO
An ethanol extract of Piper auritum leaves (PAEE) inhibits the mutagenic effect of three food-borne aromatic amines (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)) in the TA98 Salmonella typhimurium strain. Preincubation with MeIQx demonstrated in mutagenesis experiments that inhibition of Cytochrome P450 (CYP), as well as direct interaction between component(s) of the plant extract with mutagens, might account for the antimutagenic observed effect. Gas chromatography/mass spectrometry analysis revealed that safrole (50.7%), α-copaene (7.7%), caryophyllene (7.2%), ß-pinene (4.2%), γ-terpinene (4.1%), and pentadecane (4.1%) as the main components (PAEE). Piper extract and safrole were able to inhibit the rat liver microsomal CYP1A1 activity that participates in the amines metabolism, leading to the formation of the ultimate mutagenic/ molecules. According to this, safrole and PAEE-inhibited MeIQx mutagenicity but not that of the direct mutagen 2-nitrofluorene. No mutagenicity of plant extract or safrole was detected. This study shows that PAEE and its main component safrole are associated with the inhibition of heterocyclic amines activation due in part to the inhibition of CYP1A subfamily activity.
Assuntos
Piper , Extratos Vegetais , Salmonella typhimurium , Animais , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Piper/química , Antimutagênicos/farmacologia , Masculino , Mutagênicos/toxicidade , Mutagênicos/farmacologia , Quinoxalinas/farmacologia , Folhas de Planta/química , Aminas/farmacologia , Aminas/química , Etanol/química , Safrol/farmacologia , Testes de Mutagenicidade , Cromatografia Gasosa-Espectrometria de Massas , Monoterpenos Bicíclicos/farmacologiaRESUMO
Wireless communication technologies, particularly radio frequency (RF), have been widely explored for wearable electronics with secure and user-friendly information transmission. By exploiting the operational principle of chemically actuated resonant devices (CARDs) and the electrical response observed in chemiresistive materials, we propose a simple and hands-on alternative to design and manufacture RF tags that function as CARDs for wireless sensing of meat freshness. Specifically, the RF antennas were meticulously designed and fabricated by lithography onto a flexible substrate with conductive tape, and the RF signal was characterized in terms of amplitude and peak resonant frequency. Subsequently, a single-walled carbon nanotube (SWCNT)/MoS2/In2O3 chemiresistive composite was incorporated into the RF tag to convey it as CARDs. The RF signal was then utilized to establish a correlation between the sensor's electrical response and the RF attenuation signal (reflection coefficient) in the presence of volatile amines and seafood (shrimp) samples. The freshness of the seafood samples was systematically assessed throughout the storage time by utilizing the CARDs, thereby underscoring their effective potential for monitoring food quality. Specifically, the developed wireless tags provide cumulative amine exposure data within the food package, demonstrating a gradual decrease in radio frequency signals. This study illustrates the versatility of RF tags integrated with chemiresistors as a promising pathway toward scalable, affordable, and portable wireless chemical sensors.
Assuntos
Qualidade dos Alimentos , Carne , Carne/análise , AminasRESUMO
BACKGROUND: Studies suggest an interplay between maternal metabolome and mental health. OBJECTIVE: We investigated the association of maternal serum metabolome at pregnancy with anxiety scores during pregnancy and throughout the first year postpartum. METHODS: A prospective cohort of Brazilian women collected 119 serum metabolome at pregnancy (28-38 weeks) and anxiety scores measured by the State-Trait Anxiety Inventory (STAI) at pregnancy (n = 118), 1 (n = 83), 6 (n = 68), and 12 (n = 57) months postpartum. Targeted metabolomics quantified metabolites belonging to amino acids (AA), biogenic amines/amino acid-related compounds, acylcarnitines, lysophosphatidylcholines, diacyl phosphatidylcholines, alkyl:acyl phosphatidylcholines, non-hydroxylated and hydroxylated sphingomyelins [SM(OH)], and hexoses classes. Linear mixed-effect models were used to evaluate the association of metabolites and STAI scores. Hierarchical clustering and principal component analyses were employed to identify clusters and metabolites, which drove their main differences. Multiple comparison-adjusted p-values (q-value) ≤ 0.05 were considered significant. RESULTS: AA (ß = -1.44) and SM(OH) (ß = -1.49) classes showed an association with STAI scores trajectory (q-value = 0.047). Two clusters were identified based on these classes. Women in cluster 2 had decreased AA and SM(OH) concentrations and higher STAI scores (worse symptoms) trajectory (ß = 2.28; p-value = 0.041). Isoleucine, leucine, valine, SM(OH) 22:1, 22:2, and 24:1 drove the main differences between the clusters. LIMITATIONS: The target semiquantitative metabolome analysis and small sample size limited our conclusions. CONCLUSIONS: Our results suggest that AA and SM(OH) during pregnancy play a role in anxiety symptoms throughout the first year postpartum.
Assuntos
Aminoácidos , Esfingomielinas , Gravidez , Humanos , Feminino , Estudos Prospectivos , Ansiedade , Aminas , FosfatidilcolinasRESUMO
In this study, twenty free amino acids (FAA) were investigated in samples of bracatinga (Mimosa scabrella) honeydew honey (BHH) from Santa Catarina (n = 15) and Paraná (n = 13) states (Brazil), followed by chemometric analysis for geographic discrimination. The FAA determination was performed by gas chromatography-mass spectrometry (GC-MS) after using a commercial EZ:faast™ kits for GC. Eight FAA were determined, being proline, asparagine, aspartic and glutamic acids found in all BHH, with significant differences (p < 0.05). In addition, with the exception of proline, the others FAA (asparagine, aspartic and glutamic) normally showed higher concentrations in samples from Santa Catarina state, being that in these samples it was also observed higher FAA sums (963.41 to 2034.73 mg kg-1) when compared to samples from Paraná state. The variability in the results did not show a clear profile of similarity when the heatmap and hierarchical grouping were correlated with the geographic origin and the concentration of eight determined FAA. However, principal component analysis (PCA) demonstrated that serine, asparagine, glutamic acid, and tryptophan were responsible for the geographic discrimination among samples from Santa Catarina and Paraná states, since they were the dominant variables (r > 0.72) in the PCA. Therefore, these results could be useful for the characterization and authentication of BHH based on their FAA composition and geographic origin.
Assuntos
Mel , Mimosa , Mel/análise , Aminoácidos , Mimosa/química , Quimiometria , Brasil , Asparagina , Aminas , ProlinaRESUMO
Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.
Assuntos
Leishmania mexicana , Leishmaniose Cutânea , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Apoptose , Arginase , Benzimidazóis/farmacologia , AminasRESUMO
BACKGROUND: The clinical picture of coronavirus disease 2019 (COVID-19)-associated sepsis is similar to that of sepsis of other aetiologies. The present study aims to analyse the role of syndecan-1 (SDC-1) as a potential predictor of septic shock in critically ill patients with COVID-19. METHODS: This is a prospective study of 86 critically ill patients due to COVID-19 infection. Patients were followed until day 28 of hospitalization. Vascular biomarkers, such as vascular cell adhesion protein-1, SDC-1, angiopoietin-1 and angiopoietin-2, were quantified upon admission and associated with the need for vasopressors in the first 7 d of hospitalization. RESULTS: A total of 86 patients with COVID-19 (mean age 60±16 y; 51 men [59%]) were evaluated. Thirty-six (42%) patients died during hospitalization and 50 (58%) survived. The group receiving vasopressors had higher levels of D-dimer (2.46 ng/ml [interquartile range {IQR} 0.6-6.1] vs 1.01 ng/ml [IQR 0.62-2.6], p=0.019) and lactate dehydrogenase (929±382 U/l vs 766±312 U/l, p=0.048). The frequency of deaths during hospitalization was higher in the group that received vasoactive amines in the first 24 h in the intensive care unit (70% vs 30%, p=0.002). SDC-1 levels were independently associated with the need for vasoactive amines, and admission values >269 ng/ml (95% CI 0.524 to 0.758, p=0.024) were able to predict the need for vasopressors during the 7 d following admission. CONCLUSIONS: Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.
Assuntos
COVID-19 , Sepse , Choque Séptico , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Sindecana-1 , Estado Terminal , COVID-19/complicações , AminasRESUMO
Masticatory myositis is an autoimmune neuromuscular disorder that affects the muscles of mastication. The affected individual has difficulties in opening or closing the mouth, pain, and swelling in the acute phase, and significant atrophy of the affected musculature in the chronic phase. A guinea pig (Cavia porcellus) with a history of chronic hyporexia, recurrent cheek teeth overgrowth, and loss of facial silhouette, was suspected of having masticatory myositis. The disease was confirmed by computed tomography and histopathological examination of muscle fragments. The patient was treated with a protocol involving corticosteroids and gabapentin, and occlusal correction procedures.
Assuntos
Músculos da Mastigação , Miosite , Animais , Cobaias , Miosite/veterinária , Miosite/diagnóstico , Miosite/etiologia , Músculos da Mastigação/patologia , Gabapentina/uso terapêutico , Masculino , Ácidos Cicloexanocarboxílicos/uso terapêutico , Aminas/uso terapêutico , Doenças dos Roedores/diagnóstico , Doenças dos Roedores/patologia , Ácido gama-Aminobutírico/uso terapêutico , Tomografia Computadorizada por Raios X/veterinária , Corticosteroides/uso terapêutico , FemininoRESUMO
Organic electrochemical transistors (OECTs) are important devices for the development of flexible and wearable sensors due to their flexibility, low power consumption, sensitivity, selectivity, ease of fabrication, and compatibility with other flexible materials. These features enable the creation of comfortable, versatile, and efficient portable devices that can monitor and detect a wide range of parameters for various applications. Herein, we present OECTs based on PEDOT-polyamine thin films for the selective monitoring of phosphate-containing compounds. Our findings reveal that supramolecular single phosphate-amino interaction induces higher changes in the OECT response compared to ATP-amino interactions, even at submillimolar concentrations. The steric character of binding anions plays a crucial role in OECT sensing, resulting in a smaller shift in maximum transconductance voltage and threshold voltage for bulkier binding species. The OECT response reflects not only the polymer/solution interface but also events within the conducting polymer film, where ion transport and concentration are affected by the ion size. Additionally, the investigation of enzyme immobilization reveals the influence of phosphate species on the assembly behavior of acetylcholinesterase (AchE) on PEDOT-PAH OECTs, with increasing phosphate concentrations leading to reduced enzyme anchoring. These findings contribute to the understanding of the mechanisms of OECT sensing and highlight the importance of careful design and optimization of the biosensor interface construction for diverse sensing applications.
Assuntos
Acetilcolina , Técnicas Biossensoriais , Compostos Bicíclicos Heterocíclicos com Pontes , Técnicas Eletroquímicas , Fosfatos , Polímeros , Transistores Eletrônicos , Acetilcolina/análise , Acetilcolina/química , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Aminas/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Compostos Bicíclicos Heterocíclicos com Pontes/química , Técnicas Eletroquímicas/métodos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Fosfatos/química , Poliaminas/química , Polímeros/químicaRESUMO
The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing Salmonella/microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and in silico for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. In silico predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.
Assuntos
Aminas , Cafeína , Suplementos Nutricionais , Camundongos , Animais , Humanos , Cafeína/farmacologia , Camundongos Endogâmicos C3H , Suplementos Nutricionais/toxicidade , Estresse Oxidativo , Glutationa , Mutagênicos/toxicidade , Dano ao DNARESUMO
The skin of anuran species is a protective barrier against predators and pathogens, showing also chemical defense by substances that represent a potential source for bioactive substances. This review describes the current chemical and biological knowledge from the skin secretions of Leptodactylidae species, one of the most diverse neotropical frog families. These skin secretions reveal a variety of substances such as amines (12), neuropeptides (16), and antimicrobial peptides (72). The amines include histamine and its methylated derivatives, tryptamine derivatives and quaternary amines. The peptides of Leptodactylidae species show molecular weight up to 3364 Da and ocellatins are the most reported. The peptides exhibit commonly glycine (G) or glycine-valine (GV) as C-terminal amino acids, and the most common N-terminal amino acids are glutamic acid (E), lysine (K), and valine (V). The substances from Leptodactylidae species have been evaluated against pathogenic microorganisms, particularly Escherichia coli and Staphylococcus aureus, and the most active peptides showed MIC of 1-15 µM. Furthermore, some compounds showed also pharmacological properties such as immunomodulation, treatment of degenerative diseases, anticancer, and antioxidant. Currently, only 9% of the species in this family have been properly studied, highlighting a large number of unstudied species such as an entire subfamily (Paratelmatobiinae). The ecological context, functions, and evolution of peptides and amines in this family are poorly understood and represent a large field for further exploration.(AU)
Assuntos
Animais , Anuros/fisiologia , Secreções Corporais/fisiologia , Neuropeptídeos/química , Aminas/química , Peptídeos Antimicrobianos/químicaRESUMO
Monoaminergic systems are conserved in vertebrates, yet they present variations in neuroanatomy, genetic components and functions across species. MonoAmine Oxidase, or MAO, is the enzyme responsible for monoamine degradation. While mammals possess two genes, MAO-A and MAO-B, fish possess one single mao gene. To study the function of MAO and monoamine homeostasis on fish brain development and physiology, here we have generated a mao knockout line in Astyanax mexicanus (surface fish), by CRISPR/Cas9 technology. Homozygote mao knockout larvae died at 13 days post-fertilization. Through a time-course analysis, we report that hypothalamic serotonergic neurons undergo fine and dynamic regulation of serotonin level upon loss of mao function, in contrast to those in the raphe, which showed continuously increased serotonin levels - as expected. Dopaminergic neurons were not affected by mao loss-of-function. At behavioral level, knockout fry showed a transient decrease in locomotion that followed the variations in the hypothalamus serotonin neuronal levels. Finally, we discovered a drastic effect of mao knockout on brain progenitors proliferation in the telencephalon and hypothalamus, including a reduction in the number of proliferative cells and an increase of the cell cycle length. Altogether, our results show that MAO has multiple and varied effects on Astyanax mexicanus brain development. Mostly, they bring novel support to the idea that serotonergic neurons in the hypothalamus and raphe of the fish brain are different in nature and identity, and they unravel a link between monoaminergic homeostasis and brain growth.
Assuntos
Encéfalo , Serotonina , Animais , Serotonina/metabolismo , Serotonina/farmacologia , Encéfalo/metabolismo , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Monoaminoxidase/farmacologia , Aminas/farmacologia , Peixes/metabolismo , Homeostase , Mamíferos/metabolismoRESUMO
Amyloids are cytotoxic protein aggregates that deposit in human tissues, leading to several health disorders. Their aggregates can also exhibit catalytic properties, and they have been used as candidates for the development of functional biomaterials. Despite being polymorphic, amyloids often assemble as cross-ß fibrils formed by in-register ß sheet layers. Recent studies of some amyloidogenic protein segments revealed that they crystallize as antiparallel out-of-register ß sheets. Such arrangement has been proposed to be responsible for the cytotoxicity in amyloid diseases, however, there is still no consensus on the molecular mechanism. Interestingly, two amyloidogenic peptide segments, NFGAILS and FGAILSS, arrange into out-of-register and in-register ß sheets, respectively, even though they solely differ by one aminoacid residue at both termini. In this work, we used density functional theory (DFT) to address how the strand register contributes into the packing and molecular properties of the NFGAILS and FGAILSS crystals. Our results show that the out-of-register structure is substantially more stable, at 0 K, than the in-register one due to stronger inter-strand contacts. Based on an analysis of the electrostatic potential of the crystal slabs, it is suggested that the out-of-register may potentially interact with negatively charged groups, like those found in cell membranes. Moreover, calculated reactivity descriptors indicate a similar outcome, where only the out-of-register peptide exhibits intrinsic reactive surface sites at the exposed amine and carboxylic groups. It is therefore suggested that the out-of-register arrangement may indeed be crucial for amyloid cytotoxicity. The findings presented here could help to further our understanding of amyloid aggregation, function, and toxicity.
Assuntos
Amiloide , Peptídeos , Humanos , Proteínas Amiloidogênicas , Aminas , AminoácidosRESUMO
Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by motor, psychiatric, cognitive, and peripheral symptoms without effective therapy. Evidence suggests that lifestyle factors can modulate disease onset and progression, and environmental enrichment (EE) has emerged as a potential approach to mitigate the progression and severity of neurodegenerative processes. Wild-type (WT) and yeast artificial chromosome (YAC) 128 mice were exposed to different EE conditions. Animals from cohort 1 were exposed to EE between postnatal days 21 and 60, and animals from cohort 2 were exposed to EE between postnatal days 60 and 120. Motor and non-motor behavioral tests were employed to evaluate the effects of EE on HD progression. Monoamine levels, hippocampal cell proliferation, neuronal differentiation, and dendritic arborization were also assessed. Here we show that EE had an antidepressant-like effect and slowed the progression of motor deficits in HD mice. It also reduced monoamine levels, which correlated with better motor performance, particularly in the striatum. EE also modulated neuronal differentiation in the YAC128 hippocampus. These results confirm that EE can impact behavior, hippocampal neuroplasticity, and monoamine levels in YAC128 mice, suggesting this could be a therapeutic strategy to modulate neuroplasticity deficits in HD. However, further research is needed to fully understand EE's mechanisms and long-term effects as an adjuvant therapy for this debilitating condition.
Assuntos
Transtornos Heredodegenerativos do Sistema Nervoso , Doença de Huntington , Animais , Camundongos , Doença de Huntington/genética , Doença de Huntington/terapia , Aminas , Proliferação de Células , Terapia CombinadaRESUMO
Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.
Assuntos
Poluição por Fumaça de Tabaco , Gravidez , Humanos , Feminino , 8-Hidroxi-2'-Desoxiguanosina , Brasil , Placenta/química , Compostos de Anilina/análise , Aminas/toxicidade , Aminas/urina , Dano ao DNA , Fumaça/análise , Compostos Azo , Estilo de Vida , Fatores Socioeconômicos , Variação GenéticaRESUMO
Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.
Assuntos
Lisina , Proteína-Lisina 6-Oxidase , Animais , Proteína-Lisina 6-Oxidase/metabolismo , Lisina/metabolismo , Polifenóis/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Homeostase , Aminas/metabolismo , Mamíferos/metabolismoRESUMO
Amino acids (AAs) are a class of important metabolites in metabolomics methodology that investigates metabolite changes in a cell, tissue, or organism for early diagnosis of diseases. Benzo[a]pyrene (BaP) is considered a priority contaminant by different environmental control agencies because it is a proven carcinogenic compound for humans. Therefore, it is important to evaluate the BaP interference in the metabolism of amino acids. In this work, a new amino acid extraction procedure (derivatized with propyl chloroformate/propanol) using functionalized magnetic carbon nanotubes was developed and optimized. A hybrid nanotube was used followed by desorption without heating, and excellent extraction of analytes was obtained. After exposure of Saccharomyces cerevisiae, the BaP concentration of 25.0 µmol L-1 caused changes in cell viability, indicating metabolic changes. A fast and efficient GC/MS method using a Phenomenex ZB-AAA column was optimized, enabling the determination of 16 AAs in yeasts exposed or not to BaP. A comparison of AA concentrations obtained in the two experimental groups showed that glycine (Gly), serine (Ser), phenylalanine (Phe), proline (Pro), asparagine (Asn), aspartic acid (Asp), glutamic acid (Glu), tyrosine (Tyr), and leucine (Leu) statistically differentiated, after subsequent application of ANOVA with Bonferroni post-hoc test, with a confidence level of 95%. This amino acid pathway analysis confirmed previous studies that revealed the potential of these AAs as toxicity biomarker candidates.