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1.
J Colloid Interface Sci ; 607(Pt 1): 782-790, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34536935

RESUMO

HYPOTHESIS: Due to the intrinsic nature of the surface-enhanced Raman scattering (SERS), the detection of molecules with weak binding affinities toward metal substrates is critical for development of a universal SERS sensing platform. We hypothesized the physical trapping of small pesticide molecules for active hot spot generation using tyramine-mediated crosslinking chemistry and silver nanoparticles (Ag NPs) enhances SERS detection sensitivity. EXPERIMENTS: Tyramine-mediated crosslinking chemistry for sensor application was validated by ultraviolet-visible absorption spectroscopy, scanning electron microscopy, dynamic light scattering, and Raman spectroscopy. SERS sensing platform using tyramine-mediated crosslinking reaction was systematically studied for detection of 1,4-dyethylnylbenzene as a model analyte. This sensor system was applied to detect two other pesticides, thiabendazole and 1,2,3,5-tetrachlorobenzene, which have different binding affinities toward metal surfaces. FINDINGS: The SERS signal of 1,4-dyethylnylbenzene obtained using this sensor system was 3.6 times stronger than that obtained using the Ag colloidal due to the nanogap of approximately 1.3 nm within the generated hot spots. This sensor system based on tyramine-mediated crosslinked Ag NPs was evaluated as a promising tool to achieve a solution based sensitive detection of various pesticide molecules that cannot be adsorbed on the surfaces of typical SERS substrates such as metal nanoparticles.


Assuntos
Nanopartículas Metálicas , Praguicidas , Prata , Análise Espectral Raman , Tiramina
2.
Analyst ; 146(23): 7320-7326, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34762076

RESUMO

A new and simple surface-enhanced Raman scattering (SERS) biosensor based on the tyramine signal amplification (TSA)-triggered formation of horseradish peroxidase (HRP) repeats on a gold sensing chip was designed for the highly sensitive detection of hydrogen peroxide (H2O2). Initially, gold wafers were functionalized with HRP as sensing chips. Then, the HRP immobilized on the chips triggers the TSA reaction to transform the tyramine-HRP conjugate into a tyramine-HRP repeat array. With the aid of the target H2O2, the HRP repeats catalyze the oxidation of o-phenylenediamine (OPD) and produce an enzyme catalytic product with a different chemical structure, thus altering the fingerprint of the SERS spectra from that of OPD. H2O2 can be quantitatively analyzed according to the change in SERS signal intensity. On the basis of the TSA strategy, the proposed method allows the detection of H2O2 with a limit of detection (LOD) of 0.8 × 10-8 M. The as-prepared SERS sensor can achieve high-sensitivity H2O2 detection with a small amount of sample for each analysis. Therefore, this sensor exhibits significant potential for application in bioanalysis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Ouro , Peroxidase do Rábano Silvestre , Peróxido de Hidrogênio , Limite de Detecção , Análise Espectral Raman , Tiramina
3.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502468

RESUMO

In this paper, magnetic molecularly imprinted nano-conjugates were synthesized to serve as selective sorbents in a model study of tyramine determination in craft beer samples. The molecularly imprinted sorbent was characterized in terms of morphology, structure, and composition. The magnetic dispersive solid phase extraction protocol was developed and combined with liquid chromatography coupled with mass spectrometry to determine tyramine. Ten samples of craft beers were analyzed using a validated method, revealing tyramine concentrations in the range between 0.303 and 126.5 mg L-1. Tyramine limits of detection and quantification were 0.033 mg L-1 and 0.075 mg L-1, respectively. Therefore, the fabricated molecularly imprinted magnetic nano-conjugates with a fast magnetic responsivity and desirable adsorption performance could be an effective tool for monitoring tyramine levels in beverages.


Assuntos
Cerveja/análise , Fenômenos Magnéticos , Impressão Molecular , Nanoconjugados/química , Tiramina/análise
4.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445611

RESUMO

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice. Irrespective of genotype, systemic administration of o-PIT led to a similar increase in mouse brain concentrations. Consistent with the observation of a high density of TAAR1 in the medial preoptic area, o-PIT-induced hypothermia was significantly reduced in TAAR1-KO mice. Furthermore, the inhibition of a prepulse inhibition response by o-PIT, as well as its induction of striatal tyrosine hydroxylase phosphorylation and elevation of extracellular DA in prefrontal cortex, were all reduced in TAAR1-KO compared to wildtype mice. O-PIT was active in both forced-swim and marble-burying tests, and its effects were significantly blunted in TAAR1-KO mice. Conversely, the actions on behaviour and prefrontal cortex dialysis of a broad suite of clinically used antidepressants were unaffected in TAAR1-KO mice. In conclusion, o-PIT is a useful tool for exploring the hypothermic and other functional antidepressant roles of TAAR1. By contrast, clinically used antidepressants do not require TAAR1 for expression of their antidepressant properties.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/farmacologia , Receptores Acoplados a Proteínas G/fisiologia , Tiramina/análogos & derivados , Tiramina/farmacologia , Inibidores da Captação Adrenérgica/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
J Food Prot ; 84(9): 1539-1548, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375430

RESUMO

ABSTRACT: Essential foods as part of a daily meal may include numerous kinds of biogenic amines (BAs) at various concentrations. BAs have a variety of toxicological effects on human health and have been linked to multiple outbreaks of foodborne disease. BAs also are known to cause cancer based on their ability to react with nitrite salts, resulting in the production of carcinogenic organic compounds (nitrosamines). Ingestion of large quantities of BAs in food causes toxicological effects and health disorders, including psychoactive, vasoactive, and hypertensive effects and respiratory, gastrointestinal, cardiovascular, and neurological disorders. The toxicity of BAs is linked closely to the BAs histamine and tyramine. Other amines, such as phenylethylamine, putrescine, and cadaverine, are important because they can increase the negative effects of histamine. The key method for reducing BA concentrations and thus foodborne illness is management of the bacterial load in foods. Basic good handling and hygiene practices should be used to control the formation of histamine and other BAs and reduce the toxicity histamine and tyramine. A better understanding of BAs is essential to enhance food safety and quality. This review also includes a discussion of the public health implications of BAs in foods.


Assuntos
Aminas Biogênicas , Contaminação de Alimentos , Cadaverina , Histamina , Humanos , Putrescina , Tiramina
6.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361074

RESUMO

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1-20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 µM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.


Assuntos
Acetilcolinesterase/química , Alcaloides de Amaryllidaceae/química , Butirilcolinesterase/química , Inibidores da Colinesterase/farmacologia , Simulação de Acoplamento Molecular , Neuroblastoma/tratamento farmacológico , Tiramina/análogos & derivados , Proliferação de Células , Inibidores da Colinesterase/química , Simulação por Computador , Humanos , Neuroblastoma/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Tiramina/química
7.
J Neural Transm (Vienna) ; 128(11): 1741-1756, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34373944

RESUMO

The classic monoamine oxidase inhibitors (MAOIs) tranylcypromine (TCP) and phenelzine (PLZ) are powerful antidepressants that come with an equally powerful stigma, and are thus rarely prescribed-despite their well-established effectiveness. Some of these preconceptions appear to stem from unclarity, as the etiology of a rare but important side effect, 'spontaneous hypertension' (SH)-a significant increase in blood pressure absent dietary tyramine ingestion-remains improperly elucidated. This paper aims at uprooting some of the stigma surrounding MAOIs by advancing the trace amine (TA) theory as the causative underpinning of SH. This theory posits that SH results from the considerable influx of TAs observed following TCP- or PLZ-administration. TAs are known, albeit at greatly supraphysiological levels, to raise blood pressure on account of their propensity to exert potent indirect sympathomimetic effects; additionally, some research posits that TAs may induce vasoconstrictive effects partly or wholly separate therefrom, which would then constitute a second hypertensive mechanism. TAs are endogenous to the human body in low quantities. Both TCP and PLZ cause marked elevations of 2-phenylethylamine (PEA), meta- and para-tyramine (m-/p-TYR), octopamine (OA), and tryptamine (TRYP), following both acute and (sub)chronic administration. This paper holds that TYR plays a pivotal role in causing SH, due to its strong pressor effect. Cautious treatment of SH is advised, given its typically self-limiting nature. The risk of hypotensive overshoots must be taken into account. For severe cases, this paper urges reconsideration, following suitable confirmation trials, of antipsychotics (notably risperidone) as these agents may reduce striatal p-TYR levels.


Assuntos
Hipertensão , Inibidores da Monoaminoxidase , Antidepressivos , Humanos , Hipertensão/induzido quimicamente , Monoaminoxidase , Inibidores da Monoaminoxidase/efeitos adversos , Tranilcipromina , Tiramina
8.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298939

RESUMO

The present study deals with the mathematical modeling of crosslinking kinetics of polymer-phenol conjugates mediated by the Horseradish Peroxidase (HRP)-hydrogen peroxide (H2O2) initiation system. More specifically, a dynamic Monte Carlo (MC) kinetic model is developed to quantify the effects of crosslinking conditions (i.e., polymer concentration, degree of phenol substitution and HRP and H2O2 concentrations) on the gelation onset time; evolution of molecular weight distribution and number and weight average molecular weights of the crosslinkable polymer chains and gel fraction. It is shown that the MC kinetic model can faithfully describe the crosslinking kinetics of a finite sample of crosslinkable polymer chains with time, providing detailed molecular information for the crosslinkable system before and after the gelation point. The MC model is validated using experimental measurements on the crosslinking of a tyramine modified Hyaluronic Acid (HA-Tyr) polymer solution reported in the literature. Based on the rubber elasticity theory and the MC results, the dynamic evolution of hydrogel viscoelastic and molecular properties (i.e., number average molecular weight between crosslinks, Mc, and hydrogel mesh size, ξ) are calculated.


Assuntos
Ácido Hialurônico/química , Tiramina/química , Elasticidade , Peroxidase do Rábano Silvestre/química , Hidrogéis/química , Peróxido de Hidrogênio/química , Cinética , Modelos Teóricos , Método de Monte Carlo , Polímeros/química , Reologia
9.
Brain Behav Evol ; 96(1): 13-25, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265763

RESUMO

Sucrose represents an important carbohydrate source for most bee species. In the Western honeybee (Apis mellifera) it was shown that individual sucrose responsiveness correlates with the task performed in the colony, supporting the response threshold theory which states that individuals with the lowest threshold for a task-associated stimuli will perform the associated task. Tyramine was shown to modulate sucrose responsiveness, most likely via the tyramine 1 receptor. This receptor is located in brain areas important for the processing of gustatory stimuli. We asked whether the spatial expression pattern of the tyramine 1 receptor is a unique adaptation of honeybees or if its expression represents a conserved trait. Using a specific tyramine receptor 1 antibody, we compared the spatial expression of this receptor in the brain of different corbiculate bee species, including eusocial honeybees, bumblebees, stingless bees, and the solitary bee Osmia bicornis as an outgroup. We found a similar labeling pattern in the mushroom bodies, the central complex, the dorsal lobe, and the gnathal ganglia, indicating a conserved receptor expression. With respect to sucrose responsiveness this result is of special importance. We assume that the tyramine 1 receptor expression in these neuropiles provides the basis for modulation of sucrose responsiveness. Furthermore, the tyramine 1 receptor expression seems to be independent of size, as labeling is similar in bee species that differ greatly in their body size. However, the situation in the optic lobes appears to be different. Here, the lobula of stingless bees is clearly labeled by the tyramine receptor 1 antibody, whereas this labeling is absent in other species. This indicates that the regulation of this receptor is different in the optic lobes, while its function in this neuropile remains unclear.


Assuntos
Receptores de Amina Biogênica , Animais , Abelhas , Encéfalo/metabolismo , Corpos Pedunculados , Receptores de Amina Biogênica/metabolismo , Tiramina
11.
Food Microbiol ; 99: 103813, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34119100

RESUMO

Tyramine is one of the most toxic biogenic amines and it is produced commonly by lactic acid bacteria in fermented food products. In present study, we investigated the influence of selected nisin-producing Lactococcus lactis subsp. lactis strains and their cell-free supernatants (CFSs) on tyramine production by four Lactobacillus and two Lactiplantibacillus strains isolated from cheese and beer. Firstly, we examined the antimicrobial effect of the CFSs from twelve Lactococcus strains against tested tyramine producers by agar-well diffusion assay. Six Lactococcus strains whose CFSs showed the highest antimicrobial effect on tyramine producers were further studied. Secondly, we investigated the influence of the selected six Lactococcus strains and their respective CFSs on tyramine production by tested Lactobacillus and Lactiplantibacillus strains in MRS broth supplemented with 2 g.L-1 of l-tyrosine. Tyramine production was monitored by HPLC-UV. The tyramine formation of all tested Lactobacillus and Lactiplantibacillus strains was not detected in the presence of Lc. lactis subsp. lactis CCDM 71 and CCDM 702, and their CFSs. Moreover, the remainder of the investigated Lactococcus strains (CCDM 670, CCDM 686, CCDM 689 and CCDM 731) and their CFSs decreased tyramine production significantly (P < 0.05) - even suppressing it completely in some cases - in four of the six tested tyramine producing strains.


Assuntos
Antibacterianos/farmacologia , Cerveja/microbiologia , Queijo/microbiologia , Meios de Cultura/farmacologia , Lactobacillaceae/efeitos dos fármacos , Lactobacillus/efeitos dos fármacos , Lactococcus lactis/química , Tiramina/farmacologia , Antibacterianos/análise , Antibacterianos/metabolismo , Cromatografia Líquida de Alta Pressão , Meios de Cultura/química , Meios de Cultura/metabolismo , Lactobacillaceae/crescimento & desenvolvimento , Lactobacillaceae/isolamento & purificação , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/isolamento & purificação , Lactococcus lactis/metabolismo , Tiramina/análise , Tiramina/metabolismo
12.
Cell Death Dis ; 12(6): 603, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117215

RESUMO

We report the discovery of strong HNF4α agonists and their use to uncover a previously unknown pathway by which HNF4α controls the level of fat storage in the liver. This involves the induction of lipophagy by dihydroceramides, the synthesis and secretion of which is controlled by genes induced by HNF4α. The HNF4α activators are N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT), which are structurally related to the known drugs alverine and benfluorex, which we previously showed to be weak HNF4α activators. In vitro, NCT and NFT induced fat clearance from palmitate-loaded cells. In DIO mice, NCT led to recovery of hepatic HNF4α expression and reduction of steatosis. Mechanistically, increased dihydroceramide production and action downstream of HNF4α occurred through increased expression of HNF4α downstream genes, including SPNS2 and CYP26A1. NCT was completely nontoxic at the highest dose administered and so is a strong candidate for an NAFLD therapeutic.


Assuntos
Ácidos Cafeicos/farmacologia , Fator 4 Nuclear de Hepatócito/fisiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Tiramina/análogos & derivados , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Células Cultivadas , Ácidos Cumáricos/farmacologia , Células HeLa , Células Hep G2 , Fator 4 Nuclear de Hepatócito/agonistas , Fator 4 Nuclear de Hepatócito/genética , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tiramina/farmacologia
13.
PLoS Biol ; 19(5): e3001228, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33970909

RESUMO

The biogenic amine octopamine (OA) and its precursor tyramine (TA) are involved in controlling a plethora of different physiological and behavioral processes. The tyramine-ß-hydroxylase (tßh) gene encodes the enzyme catalyzing the last synthesis step from TA to OA. Here, we report differential dominance (from recessive to overdominant) of the putative null tßhnM18 allele in 2 behavioral measures in Buridan's paradigm (walking speed and stripe deviation) and in proboscis extension (sugar sensitivity) in the fruit fly Drosophila melanogaster. The behavioral analysis of transgenic tßh expression experiments in mutant and wild-type flies as well as of OA and TA receptor mutants revealed a complex interaction of both aminergic systems. Our analysis suggests that the different neuronal networks responsible for the 3 phenotypes show differential sensitivity to tßh gene expression levels. The evidence suggests that this sensitivity is brought about by a TA/OA opponent system modulating the involved neuronal circuits. This conclusion has important implications for standard transgenic techniques commonly used in functional genetics.


Assuntos
Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Alelos , Animais , Animais Geneticamente Modificados/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Feminino , Genótipo , Masculino , Mutação/genética , Octopamina/genética , Octopamina/metabolismo , Fenótipo , Receptores de Amina Biogênica/genética , Receptores de Amina Biogênica/metabolismo , Tiramina/metabolismo
14.
Food Chem ; 361: 130044, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049048

RESUMO

A method for the determination of 8 biogenic amines in aquatic products and their derived products was established by HPLC-MS/MS without derivatization. The samples were extracted by 5% perchloric acid solution. N-hexane was used to clean the extract. The analytes were separated by a column of ACQUITY UPLC HSS T3 (100 mm × 2.1 mm, 1.8 µm), and gradient eluted with a mixed solution of (0.5% formic acid) and acetonitrile. Good linearity was obtained with correlation coefficients (R2) >0.99. This method achieved higher sensitivity (from 0.1 mg/kg for tyramine, 2-phenylethylamine and tryptamine to 1.0 mg/kg for spermidine, spermine, cadaverin, histamine and putrescine). The average recoveries were demonstrated in the range of 70.9%-113.1%, with relative standard deviations (RSDs) from 0.33% to 10.81%. This method was suitable for the detection of BAs in aquatic products and their products.


Assuntos
Aminas Biogênicas/análise , Cromatografia Líquida de Alta Pressão/métodos , Alimentos Marinhos/análise , Espectrometria de Massas em Tandem/métodos , Cadaverina/análise , Histamina/análise , Fenetilaminas/análise , Putrescina/análise , Espermidina/análise , Espermina/análise , Triptaminas/análise , Tiramina/análise
15.
J Mater Chem B ; 9(20): 4211-4218, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33998627

RESUMO

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Dendrímeros/uso terapêutico , Dispositivos Lab-On-A-Chip , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anticorpos Monoclonais/química , Artrite Reumatoide/tratamento farmacológico , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Células Cultivadas , Dendrímeros/síntese química , Dendrímeros/química , Humanos , Hidrogéis/química , Inflamação/tratamento farmacológico , Nanopartículas/química , Polissacarídeos Bacterianos/química , Inibidores do Fator de Necrose Tumoral/síntese química , Inibidores do Fator de Necrose Tumoral/química , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Tiramina/química
16.
Anal Chim Acta ; 1164: 338489, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992221

RESUMO

An enzymatic method for the direct (without pretreatment) minimally invasive tyramine determination in cheese is proposed. Colorimetric test strips containing tyramine oxidase (TAO), peroxidase and 3,3',5,5'-tetramethylbenzidine (Q-TAO), allow tyramine determination through the RGB chromatic coordinates of the observed blue colour (LOD = 2.6·10-6 M, LOQ = 8.7·10-6 M, RSD% (n = 5; 1.8·10-4 M) = 3.2%). The strips are inserted in the sample for 2 min and then the RGB coordinates are measured using a smartphone. Previously, these Q-TAO strips have been also optimized for tyramine determination in cheese extract. To do that, a spectrophotometric method in solution for tyramine determination in cheese extracts has been developed, which included an in-depth study of the indicating reaction; this study has allowed to gain new information about the spectroscopic properties of different TMB species and, which it is more important, to detect cross-reactions between TAO and TMB species. A mathematical model has also been developed which relate the RGB signals obtained with the tyramine concentrations, the instrumental characteristics of the smartphone and the spectroscopic properties of the absorbing product of the enzymatic reaction.


Assuntos
Queijo , Análise de Alimentos/métodos , Tiramina/análise , Colorimetria , Peroxidase , Smartphone
17.
J Dermatol Sci ; 102(2): 78-84, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33836926

RESUMO

BACKGROUND: Psoriasis is an immune-mediated skin disease for which the crosstalk between genetic and environmental factors is responsible. To date, no definitive diagnostic criteria for psoriasis yet, and specific biomarkers are required. OBJECTIVE: We performed metabolome analysis to identify metabolite biomarkers of psoriasis and its subtypes such as psoriatic arthritis (PsA) and cutaneous psoriasis (PsC). METHODS: We constructed metabolomics profiling of 130 plasma samples (42 PsA patients, 50 PsC patients, and 38 healthy controls) using a nontargeted metabolomics approach. RESULTS: Psoriasis-control association tests showed that one metabolite (ethanolamine phosphate) was significantly increased in psoriasis samples than in the controls, whereas three metabolites decreased (false discovery rate [FDR] < 0.05; XA0019, nicotinic acid, and 20α-hydroxyprogesterone). In the association test between PsA and PsC, tyramine significantly increased in PsA than in PsC, whereas mucic acid decreased (FDR < 0.05). Molecular pathway analysis of the PsA-PsC association test identified enrichment of vitamin digestion and absorption pathway in PsC (P = 1.3 × 10-4). Correlation network analyses elucidated that a subnetwork centered on aspartate was constructed among the psoriasis-associated metabolites; meanwhile, the major subnetwork among metabolites with differences between PsA and PsC was primarily formed from saturated fatty acids. CONCLUSION: Our large-scale metabolome analysis highlights novel characteristics of plasma metabolites in psoriasis and the differences between PsA and PsC, which could be used as potential biomarkers of psoriasis and its clinical subtypes. These findings contribute to our understanding of psoriasis pathophysiology.


Assuntos
Artrite Psoriásica/diagnóstico , Psoríase/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/sangue , Artrite Psoriásica/metabolismo , Ácido Aspártico/sangue , Ácido Aspártico/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Psoríase/sangue , Psoríase/metabolismo , Índice de Gravidade de Doença , Açúcares Ácidos/sangue , Açúcares Ácidos/metabolismo , Tiramina/sangue , Tiramina/metabolismo , Adulto Jovem
18.
Elife ; 102021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890854

RESUMO

Ribonucleoprotein (RNP) granules are dynamic condensates enriched in regulatory RNA binding proteins (RBPs) and RNAs under tight spatiotemporal control. Extensive recent work has investigated the molecular principles underlying RNP granule assembly, unraveling that they form through the self-association of RNP components into dynamic networks of interactions. How endogenous RNP granules respond to external stimuli to regulate RNA fate is still largely unknown. Here, we demonstrate through high-resolution imaging of intact Drosophila brains that Tyramine induces a reversible remodeling of somatic RNP granules characterized by the decondensation of granule-enriched RBPs (e.g. Imp/ZBP1/IGF2BP) and helicases (e.g. Me31B/DDX-6/Rck). Furthermore, our functional analysis reveals that Tyramine signals both through its receptor TyrR and through the calcium-activated kinase CamkII to trigger RNP component decondensation. Finally, we uncover that RNP granule remodeling is accompanied by the rapid and specific translational activation of associated mRNAs. Thus, this work sheds new light on the mechanisms controlling cue-induced rearrangement of physiological RNP condensates.


Assuntos
Proteínas de Drosophila/metabolismo , Neurotransmissores/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/metabolismo , Ribonucleoproteínas/metabolismo , Tiramina/metabolismo , Animais , Encéfalo/metabolismo , Grânulos Citoplasmáticos , Drosophila melanogaster , Feminino , Masculino , Neurotransmissores/administração & dosagem , Tiramina/administração & dosagem
19.
Chem Res Toxicol ; 34(5): 1348-1354, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-33913699

RESUMO

Linezolid, the principal oxazolidinone antibiotic for therapy of Gram-positive infections, is limited by its myelosuppression and monoamine oxidase (MAO) inhibition, with the latter manifested as serotonergic neurotoxicity. The oral oxazolidinone contezolid and its injectable prodrug contezolid acefosamil are developed to overcome the above limitations. Serotonergic profiles for contezolid in vitro and for orally administered contezolid acefosamil in rodents are reported. Contezolid exhibited 2- and 148-fold reduction over linezolid reversible inhibition of MAO-A and MAO-B human enzyme isoforms. In the mouse head-twitch model, contezolid acefosamil was devoid of neurotoxicity at supratherapeutic oral doses of 40, 80, and 120 mg/kg. In the rat tyramine challenge model, no significant increase in arterial blood pressure was observed for contezolid acefosamil up to 120 mg/kg oral dosing. In these tests, the comparator linezolid has elicited serotonergic responses. Thus, contezolid and contezolid acefosamil exhibited an attenuated propensity to induce MAO-related serotonergic neurotoxicity. The data support a continued clinical evaluation of these agents, with potential to expand oxazolidinone therapies to patient populations on concurrent selective serotonin reuptake inhibitor medications or where MAO inhibitors are contraindicated.


Assuntos
Antibacterianos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Inibidores da Monoaminoxidase/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Oxazolidinonas/farmacologia , Piridonas/farmacologia , Administração Oral , Animais , Antibacterianos/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Estrutura Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/administração & dosagem , Oxazolidinonas/administração & dosagem , Piridonas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Tiramina/metabolismo
20.
Food Microbiol ; 98: 103762, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33875200

RESUMO

Harmful levels of biogenic amines (BAs) are frequently identified in sufu. The microorganisms and mechanisms responsible for BA production in sufu, however, are not well documented. In this study, sufu samples were randomly obtained from various regions of China. Putrescine, tyramine, and histamine were quantitated as the most abundant BAs. According to the metagenome sequencing, the abundances and diversities of genes encoding the critical enzymes in BA production were acquired. The results showed that genes encoding arginine-, ornithine-, tryptophan-, and histidine decarboxylases were the predominant amino acid decarboxylase genes. Furthermore, 34 metagenome-assembled genomes (MAGs) were generated, of which 23 encoded at least one gene involved in BA production. Genetic analysis of MAGs indicated genera affiliated with Enterococcus, Lactobacillus-related, and Lactococcus were the major histamine-synthesizing bacteria, and tyrosine may be utilized by Bacillus, Chryseobacterium, Kurthia, Lysinibacillus, Macrococcus, and Streptococcus to product tyramine. The critical species involved in two putrescine-producing pathways were also explored. In the ornithine decarboxylase pathway, Lactobacillus-related and Veillonella were predicted to be the main performers, whereas Sphingobacterium and unclassified Flavobacteriaceae were the dominant executors in the agmatine deiminase pathway. The present study not only explained the BAs formation mechanism in sufu but also identified specific bacteria used to control BAs in fermented soybean products.


Assuntos
Bactérias/genética , Bactérias/metabolismo , Aminas Biogênicas/metabolismo , Alimentos de Soja/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Aminas Biogênicas/análise , China , Fermentação , Histamina/análise , Histamina/metabolismo , Metagenoma , Metagenômica , Putrescina/análise , Putrescina/metabolismo , Alimentos de Soja/análise , Soja/metabolismo , Soja/microbiologia , Tiramina/análise , Tiramina/metabolismo
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