Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.324
Filtrar
1.
Food Chem ; 343: 128556, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183873

RESUMO

Dry and subsequent wet heating were used to glycate soy proteins with dextran or glucose, followed by fractionation based on size and solubility. Dry heating led to protein glycation (formation of furosine, Nε-(carboxymethyl)-l-lysine, Nε-(carboxyethyl)-l-lysine, and protein-bound carbonyls) and aggregation (increased particle size); while subsequent wet heating induced partial unfolding and de-aggregation. The measurable free amino group content of soy proteins changed from 0.77 to 0.14, then to 0.62 mmol/g upon dry and subsequent wet heating; this non-monotonic evolution is probably due to protein structural changes, and shows that this content should be interpreted with caution as a glycation marker. After both heating steps, the smaller-sized water-soluble fractions showed higher surface activity than the larger insoluble ones, and dextran conjugates exhibited a higher surface activity than their glucose counterparts. We thereby achieved a comprehensive understanding of the properties of various fractions in plant protein fractions, which is essential when targeting applications.


Assuntos
Proteínas de Soja/metabolismo , Cromatografia Líquida de Alta Pressão , Cor , Produtos Finais de Glicação Avançada/análise , Glicosilação , Interações Hidrofóbicas e Hidrofílicas , Lisina/análogos & derivados , Lisina/análise , Agregados Proteicos , Proteínas de Soja/química , Espectrometria de Massas em Tandem , Temperatura
2.
Food Chem ; 336: 127706, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768907

RESUMO

This research was aimed to investigate the formation of protein-bound Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) in ground pork at 121 °C (5-30 min) as affected by sugars (1-9% w/w, glucose, fructose, lactose, and sucrose).The addition of reducing sugar significantly (P < 0.05) increased the levels of CML and CEL in heat treated pork samples. Even adding 1% of glucose in pork could lead to 3.8 and 4.0 times increase in the formation rate constant (zero-order) of CML and CEL, respectively. In a typical commercial sterilization process (121 °C, 30 min), adding glucose, fructose or lactose in pork resulted in an average increase of 224-581%, 26-276%, and 8-189% CML, and 217-720%, 213%-15.8 times, and 20-150% CEL, respectively, depending on the sugar concentration. Sucrose did not promote the formation of CML and CEL in pork during heating.


Assuntos
Lisina/análogos & derivados , Carne de Porco , Esterilização/métodos , Açúcares/química , Animais , Indústria de Processamento de Alimentos/métodos , Produtos Finais de Glicação Avançada/química , Lisina/química , Carne de Porco/análise
3.
Food Chem ; 337: 127690, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795853

RESUMO

Climate and feeding influence the composition of bovine milk, which is further affected by thermal treatment inducing oxidation and Maillard reactions. This study aimed to evaluate season- and processing-related changes in the modified proteome of milk from two different feeding systems. Therefore, tryptic digests of regular and hay milk were analyzed by targeting 26 non-enzymatic modifications using LC-MS. Forty-five glycated, 48 advanced glycation endproduct (AGE-) modified, and 20 oxidized/carbonylated peptides representing 44 proteins were identified with lactosylation, formyllysine, and carboxymethyllysine being most common. The numbers and quantities of glycation- and oxidation-related modifications were similar between regular and hay milk and among seasons. The effects of pasteurization and ultra-high temperature (UHT) treatment were comparable for both milk types. In particular UHT treatment increased the numbers of identified modifications and the relative quantities of lactosylated peptides. The number of identified AGE-modified and oxidized residues increased slightly after UHT-treatment, but the contents were stable.


Assuntos
Proteínas do Leite/química , Pasteurização , Estações do Ano , Animais , Bovinos , Produtos Finais de Glicação Avançada/química , Glicosilação , Temperatura Alta , Lisina/análogos & derivados , Lisina/química , Reação de Maillard , Oxirredução
4.
J Dairy Sci ; 103(12): 11086-11093, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33069412

RESUMO

Because the conventional methods for furosine analysis are time-consuming, a modified method is presented to improve analysis efficiency. Microwave-assisted HCl hydrolysis was performed at 140, 150, and 160°C for 10 to 200 min, with 6, 8, or 9 M HCl. The hydrolysate purification process was carried out using only paper and membrane filtration. An ultra-performance liquid chromatography (UPLC) system was used to achieve rapid analysis of furosine. The results showed that microwave-assisted HCl hydrolysis at 8 M and 160°C led to a stable furosine yield and took only 40 min. The UPLC analysis was completed in 8 min. The modified method was validated and obtained limit of detection at 3 µg/L, limit of quantitation of 10 µg/L, linearity range of 0.2 to 5.0 mg/L, 80.5 to 94.2% recoveries from spiked samples, and coefficients of variation of 2.2 to 6.8%. The modified method is rapid and reliable for the determination of furosine in milk.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lisina/análogos & derivados , Micro-Ondas , Leite/química , Animais , Ácido Clorídrico , Hidrólise , Lisina/análise
5.
Parasitol Res ; 119(12): 4061-4071, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33057814

RESUMO

Lysine 2-hydroxyisobutyrylation (Khib) is a recently discovered and evolutionarily conserved form of protein post-translational modification (PTM) found in mammalian and yeast cells. Previous studies have shown that Khib plays roles in the activity of gene transcription and Khib-containing proteins are closely related to the cellular metabolism. In this study, a global Khib-containing analysis using the latest databases (ToxoDB 46, 8322 sequences, downloaded on April 16, 2020) and sensitive immune-affinity enrichment coupled with liquid chromatography-tandem mass spectrometry was performed. A total of 1078 Khib modification sites across 400 Khib-containing proteins were identified in tachyzoites of Toxoplasma gondii RH strain. Bioinformatics and functional enrichment analysis showed that Khib-modified proteins were associated with various biological processes, such as ribosome, glycolysis/gluconeogenesis, and central carbon metabolism. Interestingly, many proteins of the secretory organelles (e.g., microneme, rhoptry, and dense granule) that play roles in the infection cycle of T. gondii were found to be Khib-modified, suggesting the involvement of Khib in key biological process during T. gondii infection. We also found that histone proteins, key enzymes related to cellular metabolism, and several glideosome components had Khib sites. These results expanded our understanding of the roles of Khib in T. gondii and should promote further investigations of how Khib regulates gene expression and key biological functions in T. gondii.


Assuntos
Regulação da Expressão Gênica/genética , Lisina/análogos & derivados , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Acetilação , Animais , Carbono/metabolismo , Cromatografia de Afinidade , Cromatografia Líquida , Gluconeogênese/fisiologia , Glicólise/fisiologia , Histonas/metabolismo , Lisina/química , Espectrometria de Massas , Proteoma/análise , Proteínas de Protozoários/genética , Ribossomos/metabolismo , Toxoplasma/genética
6.
PLoS One ; 15(10): e0239414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33021980

RESUMO

PURPOSE: Radiolabeled Prostate-Specific Membrane Antigen (PSMA) PET/CT is the current standard-of-care for lesion detection in patients with biochemically recurrent (BCR) prostate cancer (PCa). However, rigorous verification of detected lesions is not always performed in routine clinical practice. To aid future 18F-radiolabeled PSMA PET/CT interpretation, we aimed to identify clinical/imaging characteristics that increase the likelihood that a PSMA-avid lesion is malignant. MATERIALS AND METHODS: 262 patients with BCR, who underwent 18F-DCFPyL PSMA PET/CT, were retrospectively analyzed. The malignant nature of 18F-DCFPyL PET-detected lesions was verified through any of the following metrics: (1) positive histopathological examination; (2) additional positive imaging; (3) a ≥50% decrease in Prostate-Specific Antigen (PSA) following irradiation of the lesion(s). RESULTS: In 226/262 PET scans (86.3%) at least one lesion suspicious for recurrent PCa was detected ('positive scan'). In 84/226 positive scans (37.2%), at least one independent verification metric was available. PSMA PET-detected lesions were most often confirmed to be malignant (PCa) in the presence of a CT-substrate (96.5% vs. 55.6% without CT-substrate), with SUVpeak ≥3.5 (91.4% vs. 60.0% with SUVpeak<3.5), in patients with a PSA-level ≥2.0 ng/mL (83.7% vs. 65.7% in patients with PSA <2.0ng/mL) and in patients with >2 PET-positive lesions (94.1% vs. 64.2% in patients with 1-2 PET-positive lesions; p<0.001-0.03). CONCLUSIONS: In this study, the clinical verification of 18F-DCFPyL PET-positive lesions in patients with BCR was performed. Diagnostic certainty of PET-detected lesions increases in the presence of characteristic abnormalities on CT, when SUVpeak is ≥3.5, when PSA-levels exceed 2.0 ng/mL or in patients with more than two PET-positive lesions.


Assuntos
Lisina/análogos & derivados , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Ureia/análogos & derivados , Idoso , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Int J Nanomedicine ; 15: 7719-7743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116497

RESUMO

Objective: The anticancer efficacy of orally administered chemotherapeutics is often constrained by low intestinal membrane permeability and oral bioavailability. In this context, we designed a solid oral formulation of oxaliplatin (OP), a third-generation cisplatin analog, to improve oral bioavailability and investigate its application in metronomic chemotherapy. Methods: An ion-pairing complex of OP with a permeation enhancer, N α-deoxycholyl-l-lysyl-methylester (DLM), was successfully prepared and then mixed with dispersing agents (including poloxamer 188 and Labrasol) to form the solid, amorphous oral formulation OP/DLM (OP/DLM-SF; hereafter, ODSF). Results: The optimized powder formulation was sized in the nanoscale range (133±1.47 nm). The effective permeability of OP increased by 12.4-fold after ionic complex formation with DLM and was further increased by 24.0-fold after incorporation into ODSF. ODSF exhibited respective increases of 128% and 1010% in apparent permeability across a Caco-2 monolayer, compared to OP/DLM and OP. Furthermore, inhibition of bile acid transporters by actinomycin D and caveola-mediated uptake by brefeldin in Caco-2 cell monolayers reduced the apparent permeability values of ODSF by 58.4% and 51.1%, respectively, suggesting predominant roles for bile acid transporters and caveola-mediated transport in intestinal absorption of ODSF. In addition, macropinocytosis and paracellular and transcellular passive transport significantly influenced the intestinal permeation of ODSF. The oral bioavailabilities of ODSF in rats and monkeys were 68.2% and 277% higher, respectively, than the oral bioavailability of free OP. In vivo analyses of anticancer efficacy in CT26 and HCT116 cell-bearing mice treated with ODSF demonstrated significant suppression of tumor growth, with respective maximal tumor volume reductions of 7.77-fold and 4.07-fold, compared to controls. Conclusion: ODSF exhibits therapeutic potential, constituting an effective delivery system that increases oral bioavailability, with applications to metronomic chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Oxaliplatina/administração & dosagem , Oxaliplatina/farmacocinética , Administração Metronômica , Administração Oral , Animais , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Células CACO-2 , Permeabilidade da Membrana Celular/efeitos dos fármacos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Feminino , Glicerídeos/química , Humanos , Absorção Intestinal/efeitos dos fármacos , Lisina/análogos & derivados , Lisina/química , Macaca fascicularis , Masculino , Camundongos Endogâmicos BALB C , Poloxâmero/química , Ratos Sprague-Dawley
8.
J Nutr ; 150(10): 2799-2805, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32840609

RESUMO

BACKGROUND: Although endogenous advanced glycation end products (AGEs) have been implicated in the development of various chronic diseases, whether AGEs in foods represent a risk to human health remains unknown. OBJECTIVES: We aimed to estimate the intake of Nε-carboxymethyl-lysine (CML), a major AGE product, using a database of CML contents on LC-MS methods, and to examine CML's association with total and cause-specific mortality in Japanese adults. METHODS: The analysis included 13,355 men and 15,724 women, aged 35 years and older, from the Takayama study. They responded to a self-administered questionnaire in 1992. Their diet, including the CML intake, was assessed using a food-frequency questionnaire at baseline. Mortality was ascertained during 16 years of follow-up. HRs and 95% CIs for mortality were estimated separately for men and women according to CMI quartiles. RESULTS: We noted 2901 deaths in men and 2438 deaths in women during the follow-up. In men, as compared with the lowest quartile of intake, the highest quartile of CML was inversely associated with the risks of both total and non-cancer, non-cardiovascular disease mortality after controlling for covariates [HR = 0.89 (95% CI, 0.79-1.00; P-trend = 0.047) and HR = 0.74 (95% CI, 0.58-0.94; P-trend = 0.03), respectively]. However, stratified analyses showed both inverse and positive associations between CML intake and cause-specific mortality in women, depending on their characteristics. For example, years of education had a modifying effect on both the CML intake and non-cancer, non-cardiovascular disease mortality in women. In men, the associations of CML intake with mortality depended on food sources. CONCLUSIONS: Overall, the present study does not support a positive association between CML intake and mortality in Japanese adults. The potential relevance of the food source of CML to the link between dietary CML and mortality warrants further attention.


Assuntos
Dieta , Produtos Finais de Glicação Avançada/efeitos adversos , Lisina/análogos & derivados , Mortalidade , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Japão , Lisina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
9.
Plant Physiol Biochem ; 155: 444-454, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32818792

RESUMO

Two Fabaceae exhibiting rapid osmocontractile pulvinar movements were used in this study because this activity is modified by natural auxin and dramatically by 2,4D. A short chain with a carboxylic group being required for auxinic properties, a critical point to analyze is whether the recently synthesized proherbicide ε-(2,4-dichlorophenoxyacetyl)-L-Lys (2-4D-L-Lys) maintains some biological activity despite the increase in length of the chain and the substitution of the carboxyl group by an α-amino acid function. No trace of 2,4D could be detected in the pulvinar tissues treated for 1 h with 2,4D-L-Lys. Complementary approaches (electrophysiology, pH measurements, use of plasma membrane vesicles) suggest that it was less efficient than 2,4D to activate the plasma membrane H+-ATPase (PM-H+-ATPase). However, it modified the various ion-driven reactions of Mimosa pudica and Cassia fasciculata pulvini in a similar way as 2,4D. Additionally, it was much more effective than fusicoccin to inhibit seismonastic movements of M. pudica leaves and, at low concentrations, to promote leaflet opening in dark, indicating that its mode of action is more complex than the only activation of the PM-H+-ATPase. Various substitutions on 2,4D-L-Lys affected its activity in correlation with the molecular descriptor "halogen ratio" of these derivatives. Conjugation with D-Lys also led to a decrease of pulvinar reaction, suggesting that 2,4D-Lys maintains the main signaling properties of 2,4D involved in pulvinar movements providing that the terminal zwitterion is in a suitable orientation. Our data guide future investigations on the effect of 2,4D and 2,4D-L-Lys on the vacuolar pump activity of motor cells.


Assuntos
Cassia/efeitos dos fármacos , Herbicidas/química , Mimosa/efeitos dos fármacos , Células Vegetais/efeitos dos fármacos , Ácido 2,4-Diclorofenoxiacético/química , Membrana Celular/metabolismo , Lisina/análogos & derivados , Lisina/química , ATPases Translocadoras de Prótons/metabolismo
10.
AJR Am J Roentgenol ; 215(3): 652-659, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755168

RESUMO

OBJECTIVE. The purpose of this study was to assess the utility of PET with (2S)-2-[[(1S)-1-carboxy-5-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]pentyl]carbamoylamino]pentanedioic acid (18F-DCFPyL), a prostate-specific membrane antigen (PSMA)-targeted radiotracer, in the detection of high-risk localized prostate cancer as compared with multiparametric MRI (mpMRI). SUBJECTS AND METHODS. This HIPAA-compliant prospective study included 26 consecutive patients with localized high-risk prostate cancer (median age, 69.5 years [range, 53-81 years]; median prostate-specific antigen [PSA] level, 18.88 ng/mL [range, 1.03-20.00 ng/mL]) imaged with 18F-DCFPyL PET/CT and mpMRI. Images from PET/CT and mpMRI were evaluated separately, and suspicious areas underwent targeted biopsy. Lesion-based sensitivity and tumor detection rate were compared for PSMA PET and mpMRI. Standardized uptake value (SUV) and PSMA PET parameters were correlated with histopathology score, and uptake in tumor was compared with that in nonmalignant tissue. On a patient level, SUV and PSMA tumor volume were correlated with PSA density. RESULTS. Forty-four tumors (one in Gleason grade [GG] group 1, 12 in GG group 2, seven in GG group 3, nine in GG group 4, and 15 in GG group 5) were identified at histopathology. Sensitivity and tumor detection rate of 18F-DCFPyL PET/CT and mpMRI were similar (PET/CT, 90.9% and 80%; mpMRI, 86.4% and 88.4%; p = 0.58/0.17). Total lesion PSMA and PSMA tumor volume showed a relationship with GG (τ = 0.27 and p = 0.08, τ = 0.30 and p = 0.06, respectively). Maximum SUV in tumor was significantly higher than that in nonmalignant tissue (p < 0.05). Tumor burden density moderately correlated with PSA density (r = 0.47, p = 0.01). Five true-positive tumors identified on 18F-DCFPyL PET/CT were not identified on mpMRI. CONCLUSION. In patients with high-risk prostate cancer, 18F-DCFPyL PET/CT is highly sensitive in detecting intraprostatic tumors and can detect tumors missed on mpMRI. Measured uptake is significantly higher in tumor tissue, and PSMA-derived tumor burden is associated with severity of disease.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Humanos , Lisina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Carga Tumoral , Ureia/análogos & derivados
11.
Sci Rep ; 10(1): 13046, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747680

RESUMO

Histone lysine acetyltransferase (KAT)-catalyzed acetylation of lysine residues in histone tails plays a key role in regulating gene expression in eukaryotes. Here, we examined the role of lysine side chain length in the catalytic activity of human KATs by incorporating shorter and longer lysine analogs into synthetic histone H3 and H4 peptides. The enzymatic activity of MOF, PCAF and GCN5 acetyltransferases towards histone peptides bearing lysine analogs was evaluated using MALDI-TOF MS assays. Our results demonstrate that human KAT enzymes have an ability to catalyze an efficient acetylation of longer lysine analogs, whereas shorter lysine analogs are not substrates for KATs. Kinetics analyses showed that lysine is a superior KAT substrate to its analogs with altered chain length, implying that lysine has an optimal chain length for KAT-catalyzed acetylation reaction.


Assuntos
Biocatálise , Histona Acetiltransferases/metabolismo , Lisina/química , Histonas/química , Histonas/metabolismo , Humanos , Cinética , Lisina/análogos & derivados
12.
Food Chem ; 333: 127499, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673957

RESUMO

This study was to examine the formation of advanced glycation end-products (AGEs) in black tea during drying process at 90, 120, and 150 °C for 1 h. Nine AGEs including Nɛ-(carboxyethyl)-l-lysine (CEL), Nɛ-(carboxymethyl)-l-lysine (CML), three isomers of methylglyoxal-hydroimidazolones (MG-Hs), three isomers of glyoxal-hydroimidazolones (GO-Hs), and argpyrimidine were quantified by using HPLC-MS/MS with isotope-labelled internal standard. Results showed that each AGE during the drying process of 150 °C was significantly higher (p < 0.05) than at 90 and 120 °C, and argpyrimidine was only found in the treatment of 150 °C. MG-H1/3 was first quantified as the major AGE during drying at 120-150 °C, the content respectively reached to (39.66 ± 2.61) µg/g and (58.88 ± 1.76) µg/g after 1 h drying, where CML content only had (19.86 ± 1.02) µg/g and (23.71 ± 1.40) µg/g. This study indicated that arginine derived-AGEs are the key components of black tea AGEs.


Assuntos
Camellia sinensis/química , Produtos Finais de Glicação Avançada/análise , Imidazóis/química , Lisina/análogos & derivados , Extratos Vegetais/química , Aldeído Pirúvico/química , Cromatografia Líquida de Alta Pressão , Dessecação , Manipulação de Alimentos , Humanos , Isomerismo , Lisina/química , Folhas de Planta/química , Espectrometria de Massas em Tandem , Chá
13.
Food Chem ; 332: 127387, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32629331

RESUMO

The simultaneous formation of acrylamide; ß-carboline heterocyclic amines (HAs): harmane and norharmane; and advanced glycation end products (AGEs) (Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL)) was analyzed based on an aqueous model system. The model systems included lysine-glucose (Lys/Glu), asparagine-glucose (Asn/Glu), tryptophan-glucose (Trp/Glu), and a mixture of these amino acids (Mix/Glu). Only AGEs were generated when heated at 100 °C, Asn and Trp competed with Lys for glucose and methylglyoxal (MGO), and glyoxal (GO) decreased AGE content. The k value of CML, CEL, and acrylamide decreased when heated at 130 °C, whereas that of harmane increased in the Mix/Glu, owing to the competition between Lys and Asn for glucose, GO, and MGO. Harmane preferably formed via the Pictet-Spengler condensation between Trp and acetaldehyde, which further reduced acrylamide formation via the acrolein pathway.


Assuntos
Acrilamida/análise , Aminas/análise , Produtos Finais de Glicação Avançada/análise , Reação de Maillard , Asparagina/química , Carbolinas/análise , Carbolinas/química , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Glucose/química , Harmina/análogos & derivados , Harmina/análise , Harmina/metabolismo , Temperatura Alta , Lisina/análogos & derivados , Lisina/análise , Modelos Biológicos , Aldeído Pirúvico/química
14.
Radiology ; 296(3): 564-572, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32633674

RESUMO

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of 18F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer. Materials and Methods Men were prospectively recruited after prostatectomy and/or radiation therapy with rising prostate-specific antigen level (median, 2.27 ng/mL; range, 0.2-27.45 ng/mL) and a negative result at conventional imaging (bone scan and/or CT). Participants underwent 18F-DCFPyL PET/CT imaging and 3.0-T pelvic multiparametric MRI. Statistical analysis included Wald and modified χ2 tests. Results A total of 323 lesions were visualized in 77 men by using 18F-DCFPyL or multiparametric MRI, with imaging detection concordance of 25% (82 of 323) when including all lesions in the MRI field of view and 53% (52 of 99) when only assessing prostate bed lesions. 18F-DCFPyL depicted more pelvic lymph nodes than did MRI (128 vs 23 nodes). Histologic validation was obtained in 80 locations with sensitivity, specificity, and PPV of 69% (25 of 36; 95% confidence interval [CI]: 51%, 88%), 91% (40 of 44; 95% CI: 74%, 98%), and 86% (25 of 29; 95% CI: 73%, 97%) for 18F-DCFPyL and 69% (24 of 35; 95% CI: 50%, 86%), 74% (31 of 42; 95% CI: 42%, 89%), and 69% (24 of 35; 95% CI: 50%, 88%) for multiparametric MRI (P = .95, P = .14, and P = .07, respectively). In the prostate bed, sensitivity, specificity, and PPV were 57% (13 of 23; 95% CI: 32%, 81%), 86% (18 of 21; 95% CI: 73%, 100%), and 81% (13 of 16; 95% CI: 59%, 100%) for 18F-DCFPyL and 83% (19 of 23; 95% CI: 59%, 100%), 52% (11 of 21; 95% CI: 29%, 74%), and 66% (19 of 29; 95% CI: 44%, 86%) for multiparametric MRI (P = .19, P = .02, and P = .17, respectively). The addition of 18F-DCFPyL to multiparametric MRI improved PPV by 38% overall (P = .02) and by 30% (P = .09) in the prostate bed. Conclusion Findings with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were histologically validated and demonstrated high specificity and positive predictive value. In the pelvis, 18F-DCFPyL depicted more lymph nodes and improved positive predictive value and specificity when added to multiparametric MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zukotynski and Rowe in this issue.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Próstata , Neoplasias da Próstata , Idoso , Meios de Contraste/uso terapêutico , Humanos , Lisina/análogos & derivados , Lisina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/química , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Sensibilidade e Especificidade , Ureia/análogos & derivados , Ureia/uso terapêutico
15.
Clin Nucl Med ; 45(9): 727-729, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32520499

RESUMO

A 51-year-old man diagnosed with high-grade, high-volume metastatic castration-sensitive prostate adenocarcinoma received pelvic radiation, androgen deprivation therapy, and intravenous docetaxel. Serum prostate-specific antigen became undetectable following treatment. Within a year, his cancer progressed to castration-resistant disease, and he was treated with oral abiraterone acetate 1000 mg and prednisone 10 mg daily. Despite this, the serum prostate-specific antigen rose from 0.03 to 1.39 µg/L, and F-DCFPyL and F-FDG PET/CT showed progression. While F-DCFPyL uptake may be seen in aggressive disease, F-FDG portends poor prognosis. Despite intravenous platinum-based chemotherapy, the patient died of respiratory failure 20 months after his initial diagnosis.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Lisina/análogos & derivados , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Ureia/análogos & derivados , Progressão da Doença , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico
16.
Neurol Neurochir Pol ; 54(4): 323-328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32510570

RESUMO

Atrial fibrillation (AF) and atherosclerotic disease are independent risk factors for acute ischaemic stroke (AIS). The optimal biological marker which could allow differentiation between AF and non-AF AIS patients is still not available. AIM OF THE STUDY: Aim of the present study was to investigate the role of pentosidine as a potential biological marker for AF in an AIS patient group. MATERIALS AND METHODS: Sixty-three acute ischaemic hemispheric stroke patients were recruited and divided into two groups according to the presumed underlying mechanism: with or without atrial rhythm disorders. Ten healthy volunteers were a reference group for serum level of pentosidine. Carotid artery ultrasound was performed, and common carotid artery stiffness and intima-media thickness were measured. Serum levels of pentosidine and selected routine biochemical risk factors for atherosclerosis (cholesterol and its lipoprotein fractions, homocysteine) were examined. RESULTS: A higher serum level of pentosidine was observed in patients without atrial fibrillation (1,509 ± 485.13pmol/ml); a statistically significant difference was observed compared to the reference group (1,041.52 ± 411.17pmol/ml; p = 0.01), but not the AF patients (1,438.19 ± 495.97pmol/ml; p = 0.59). No significant difference in the non-AF group compared to the AF group for carotid intima-media thickness (IMT)/stiffness and pentosidine serum level was recorded. CONCLUSIONS AND CLINICAL IMPLICATIONS: A higher serum level of pentosidine was observed in AIS patients without atrial fibrillation compared to the healthy volunteers. According to the results of the present study, no difference between these patients in the selected risk factors of atherosclerosis were observed. Further studies are needed to identify a reliable marker of AF that would bring added value to the standard diagnostic workup after acute ischaemic stroke.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , Acidente Vascular Cerebral , Arginina/análogos & derivados , Espessura Intima-Media Carotídea , Humanos , Lisina/análogos & derivados , Fatores de Risco
17.
Nat Commun ; 11(1): 3154, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572025

RESUMO

An orthogonal aminoacyl-tRNA synthetase/tRNA pair is a crucial prerequisite for site-specific incorporation of unnatural amino acids. Due to its high codon suppression efficiency and full orthogonality, the pyrrolysyl-tRNA synthetase/pyrrolysyl-tRNA pair is currently the ideal system for genetic code expansion in both eukaryotes and prokaryotes. There is a pressing need to discover or engineer other fully orthogonal translation systems. Here, through rational chimera design by transplanting the key orthogonal components from the pyrrolysine system, we create multiple chimeric tRNA synthetase/chimeric tRNA pairs, including chimera histidine, phenylalanine, and alanine systems. We further show that these engineered chimeric systems are orthogonal and highly efficient with comparable flexibility to the pyrrolysine system. Besides, the chimera phenylalanine system can incorporate a group of phenylalanine, tyrosine, and tryptophan analogues efficiently in both E. coli and mammalian cells. These aromatic amino acids analogous exhibit unique properties and characteristics, including fluorescence, post-translation modification.


Assuntos
Aminoácidos/biossíntese , Código Genético , RNA de Transferência , Biologia Sintética/métodos , Alanina/análogos & derivados , Quimera/genética , Quimera/metabolismo , Escherichia coli , Células HEK293 , Histidina/análogos & derivados , Humanos , Lisina/análogos & derivados , Fenilalanina/análogos & derivados , RNA de Transferência/genética , RNA de Transferência/metabolismo , Triptofano/análogos & derivados , Tirosina/análogos & derivados
18.
PLoS One ; 15(5): e0233052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413095

RESUMO

Severe influenza virus (IV) infections still represent a major challenge to public health. To combat IV infections, vaccines and antiviral compounds are available. However, vaccine efficacies vary with very limited to no protection against newly emerging zoonotic IV introductions. In addition, the development of resistant virus variants against currently available antivirals can be rapidly detected, in consequence demanding the design of novel antiviral strategies. Virus supportive cellular signaling cascades, such as the NF-κB pathway, have been identified to be promising antiviral targets against IV in in vitro and in vivo studies and clinical trials. While administration of NF-κB pathway inhibiting agents, such as LASAG results in decreased IV replication, it remained unclear whether blocking of NF-κB might sensitize cells to secondary bacterial infections, which often come along with viral infections. Thus, we examined IV and Staphylococcus aureus growth during LASAG treatment. Interestingly, our data reveal that the presence of LASAG during superinfection still leads to reduced IV titers. Furthermore, the inhibition of the NF-κB pathway resulted in decreased intracellular Staphylococcus aureus loads within epithelial cells, indicating a dependency on the pathway for bacterial uptake. Unfortunately, so far it is not entirely clear if this phenomenon might be a drawback in bacterial clearance during infection.


Assuntos
Antivirais/efeitos adversos , Aspirina/análogos & derivados , Infecções Bacterianas/etiologia , Glicina/efeitos adversos , Influenza Humana/tratamento farmacológico , Lisina/análogos & derivados , NF-kappa B/antagonistas & inibidores , Células A549 , Aspirina/efeitos adversos , Combinação de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Técnicas de Silenciamento de Genes , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/complicações , Influenza Humana/virologia , Lisina/efeitos adversos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Infecções Estafilocócicas/etiologia , Superinfecção/etiologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Replicação Viral/efeitos dos fármacos
19.
Nat Chem ; 12(6): 535-544, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32472101

RESUMO

Expanding and reprogramming the genetic code of cells for the incorporation of multiple distinct non-canonical amino acids (ncAAs), and the encoded biosynthesis of non-canonical biopolymers, requires the discovery of multiple orthogonal aminoacyl-transfer RNA synthetase/tRNA pairs. These pairs must be orthogonal to both the host synthetases and tRNAs and to each other. Pyrrolysyl-tRNA synthetase (PylRS)/PyltRNA pairs are the most widely used system for genetic code expansion. Here, we reveal that the sequences of ΔNPylRS/ΔNPyltRNA pairs (which lack N-terminal domains) form two distinct classes. We show that the measured specificities of the ΔNPylRSs and ΔNPyltRNAs correlate with sequence-based clustering, and most ΔNPylRSs preferentially function with ΔNPyltRNAs from their class. We then identify 18 mutually orthogonal pairs from the 88 ΔNPylRS/ΔNPyltRNA combinations tested. Moreover, we generate a set of 12 triply orthogonal pairs, each composed of three new PylRS/PyltRNA pairs. Finally, we diverge the ncAA specificity and decoding properties of each pair, within a triply orthogonal set, and direct the incorporation of three distinct non-canonical amino acids into a single polypeptide.


Assuntos
Aminoácidos/genética , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/genética , Código Genético , RNA de Transferência/genética , Aminoácidos/química , Evolução Molecular Direcionada , Escherichia coli/genética , Euryarchaeota/genética , Proteínas de Fluorescência Verde/genética , Lisina/análogos & derivados , Lisina/química , Lisina/genética , Modelos Moleculares , RNA de Transferência/química , Análise de Sequência de Proteína , Especificidade por Substrato
20.
J Stroke Cerebrovasc Dis ; 29(8): 104818, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439352

RESUMO

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.


Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Cinamatos/farmacologia , Depsídeos/farmacologia , Suplementos Nutricionais , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Aldeídos/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Camundongos Endogâmicos C57BL
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA