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1.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 493-496, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964890

RESUMO

Hypoalbuminemia is one of the important clinical features of decompensated cirrhosis. As the disease progresses, not only does the total albumin concentration decrease, but so does the proportion of albumin that remains structurally and functionally intact. The structural and functional integrity of albumin is essential for its normal physiological role in the body. This led to the concept of "effective albumin concentration," which may be much lower than the total albumin concentration routinely measured clinically in patients with advanced cirrhosis. Liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance (EMR) are emerging technologies for effective albumin concentration detection, showing promising clinical application prospects, but research in patients with cirrhosis is still in the preliminary stage. Therefore, this article will comprehensively summarize the latest research on the aspects of effective albumin detection methods, liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance, as well as their applications.


Assuntos
Espectrometria de Massas em Tandem , Humanos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Albumina Sérica/análise , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/sangue
2.
BMC Vet Res ; 20(1): 292, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970022

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. RESULTS: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.


Assuntos
Cardiomiopatia Hipertrófica , Doenças do Gato , Produtos de Degradação da Fibrina e do Fibrinogênio , Proteômica , Animais , Gatos , Doenças do Gato/sangue , Cardiomiopatia Hipertrófica/veterinária , Cardiomiopatia Hipertrófica/sangue , Masculino , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Coagulação Sanguínea/fisiologia , Tempo de Protrombina/veterinária , Biomarcadores/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Espectrometria de Massas em Tandem/veterinária
3.
J Nippon Med Sch ; 91(3): 261-269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972738

RESUMO

BACKGROUND: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood. METHODS: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-ß2-microglobulin antibodies in 40 autopsy cases. RESULTS: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis. CONCLUSIONS: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.


Assuntos
Amiloidose , Imuno-Histoquímica , Proteômica , Espectrometria de Massas em Tandem , Humanos , Imuno-Histoquímica/métodos , Espectrometria de Massas em Tandem/métodos , Proteômica/métodos , Amiloidose/diagnóstico , Amiloidose/metabolismo , Amiloidose/patologia , Cromatografia Líquida/métodos , Feminino , Idoso de 80 Anos ou mais , Masculino , Idoso , Pessoa de Meia-Idade , Autopsia , Amiloide/metabolismo , Amiloide/análise , Estudos Retrospectivos , Microglobulina beta-2/análise , Microglobulina beta-2/metabolismo , Proteína Amiloide A Sérica/análise , Adulto
4.
World J Microbiol Biotechnol ; 40(9): 262, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972951

RESUMO

Pseudomonas aeruginosa PR23 isolated from the hydrocarbon contaminated soil can tolerate and degrade mixture of polyaromatic hydrocarbons (PAHs) at an initial concentration of 1300 ppm. The degradation and intermediates formed were assessed by gas chromatography-mass spectrometry (GC-MS) analysis. The isolated strain was able to degrade 59.2% of the mixture of PAHs in 3 days and 71.6% by day 15. Effect of PAHs on protein expression in Pseudomonas aeruginosa PR23 was studied using nano LC-MS/MS. Thirty-six proteins showed a more than 2-fold increase in expression in the presence of mixture of PAHs. Out of these proteins, 7 proteins have been reported for their role in degradation of naphthalene, phenanthrene, and pyrene. The data revealed the presence of 16 proteins that were uniquely expressed in the presence of mixture of PAHs. A twin-arginine translocation signal peptide (Tat system), known for the transportation of folded proteins across the cell membrane, showed more than 8-fold increased expression in the presence of mixture of PAHs. These results indicate that the isolated strain adopts the conditions in the presence of mixture of PAHs by modulating its metabolic and physiological processes. These findings suggest that Pseudomonas aeruginosa PR23 may be a suitable candidate for use in the development of strategies for bioremediation of mixtures of PAHs.


Assuntos
Proteínas de Bactérias , Biodegradação Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Pseudomonas aeruginosa , Microbiologia do Solo , Poluentes do Solo , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Poluentes do Solo/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Cromatografia Gasosa-Espectrometria de Massas , Fenantrenos/metabolismo , Espectrometria de Massas em Tandem , Naftalenos/metabolismo
5.
Nat Commun ; 15(1): 5627, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965283

RESUMO

Glycosphingolipids (GSLs) are essential components of cell membranes, particularly enriched in the nervous system. Altered molecular distributions of GSLs are increasingly associated with human diseases, emphasizing the significance of lipidomic profiling. Traditional GSL analysis methods are hampered by matrix effect from phospholipids and the difficulty in distinguishing structural isomers. Herein, we introduce a highly sensitive workflow that harnesses magnetic TiO2 nanoparticle-based selective enrichment, charge-tagging Paternò-Büchi reaction, and liquid chromatography-tandem mass spectrometry. This approach enables mapping over 300 distinct GSLs in brain tissues by defining sugar types, long chain bases, N-acyl chains, and the locations of desaturation and hydroxylation. Relative quantitation of GSLs across multiple structural levels provides evidence of dysregulated gene and protein expressions of FA2H and CerS2 in human glioma tissue. Based on the structural features of GSLs, our method accurately differentiates human glioma with/without isocitrate dehydrogenase genetic mutation, and normal brain tissue.


Assuntos
Encéfalo , Glioma , Glicoesfingolipídeos , Humanos , Glicoesfingolipídeos/metabolismo , Glicoesfingolipídeos/química , Glioma/metabolismo , Glioma/genética , Glioma/patologia , Encéfalo/metabolismo , Lipidômica/métodos , Espectrometria de Massas em Tandem/métodos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Cromatografia Líquida/métodos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Animais , Camundongos
6.
Sci Rep ; 14(1): 15388, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965296

RESUMO

Ectothermic animals that live in seasonally cold regions must adapt to seasonal variation and specific environmental conditions. During the winter, some amphibians hibernate on land and encounter limited environmental water, deficient oxygen, and extremely low temperatures that can cause the whole body freezing. These stresses trigger physiological and biochemical adaptations in amphibians that allow them to survive. Rana sylvatica, commonly known as the wood frog, shows excellent freeze tolerance. They can slow their metabolic activity to a near halt and endure freezing of 65-70% of their total body water as extracellular ice during hibernation, returning to normal when the temperatures rise again. To investigate the molecular adaptations of freeze-tolerant wood frogs, a comprehensive proteomic analysis was performed on frog liver tissue after anoxia, dehydration, or freezing exposures using a label-free LC-MS/MS proteomic approach. Quantitative proteomic analysis revealed that 87, 118, and 86 proteins were significantly upregulated in dehydrated, anoxic, and frozen groups, suggesting potential protective functions. The presence of three upregulated enzymes, glutathione S-transferase (GST), aldolase (ALDOA), and sorbitol dehydrogenase (SORD), was also validated. For all enzymes, the specific enzymatic activity was significantly higher in the livers of frozen and anoxic groups than in the controls. This study reveals that GST, ALDOA, and SORD might participate in the freeze tolerance mechanism by contributing to regulating cellular detoxification and energy metabolism.


Assuntos
Desidratação , Congelamento , Hipóxia , Fígado , Proteômica , Ranidae , Animais , Fígado/metabolismo , Proteômica/métodos , Ranidae/metabolismo , Desidratação/metabolismo , Hipóxia/metabolismo , Proteoma/metabolismo , Espectrometria de Massas em Tandem , Resposta ao Choque Frio
7.
Sci Rep ; 14(1): 15381, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965294

RESUMO

The antiviral properties of the flowering aerial extracts of Ruellia tuberosa and Ruellia patula were investigated through phytochemical profiling via LC-MS/MS and HPLC techniques. Qualitative LC-MS/MS analyses identified seventy-seven metabolites from both Ruellia species. R. tuberosa had the highest phenolic content (49.3%), whereas R. patula had the highest flavonoid content (57.8%). Additionally, quantitative HPLC investigations of the compounds identified by LC-MS/MS were performed using the available standard compounds. The main constituents in the R. tuberosa extract was found to be catechin (5321.63 µg/g), gallic acid (2878.71 µg/g), and ellagic acid (2530.79 µg/g), whereas the major compounds in the R. patula extract was found to be rutin (11,074.19 µg/g) and chlorogenic acid (3157.35 µg/g). Furthermore, the antiviral activities of both Ruellia species against HAdV-40, herpes simplex type 2 and H1N1 were evaluated. These findings demonstrated that R. tuberosa was more active than R. patula against all tested viruses, except for the HSV-2 virus, against which R. patula showed greater activity than R. tuberosa, with IC50 values of 20, 65, 22.59, and 13.13 µg/ml for R. tuberosa flowering aerial parts and 32.26, 11.66, and 23.03 µg/ml for R. patula flowering aerial parts, respectively for HAdV-40, herpes simplex type 2, and H1N1. Additionally, computational docking and molecular dynamics simulations were used to assess the molecular interactions between the bioactive compounds and specific viral targets. The combined findings from the in-vitro and in-silico experiments comprehensively evaluated the antiviral activities of both Ruellia species extracts.


Assuntos
Antivirais , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Extratos Vegetais , Antivirais/farmacologia , Antivirais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Apiaceae/química , Espectrometria de Massas em Tandem , Simulação de Dinâmica Molecular , Cromatografia Líquida de Alta Pressão , Fenóis/química , Fenóis/farmacologia , Flavonoides/química , Flavonoides/farmacologia
8.
Sci Rep ; 14(1): 15000, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951578

RESUMO

The primary objective of analyzing the data obtained in a mass spectrometry-based proteomic experiment is peptide and protein identification, or correct assignment of the tandem mass spectrum to one amino acid sequence. Comparison of empirical fragment spectra with the theoretical predicted one or matching with the collected spectra library are commonly accepted strategies of proteins identification and defining of their amino acid sequences. Although these approaches are widely used and are appreciably efficient for the well-characterized model organisms or measured proteins, they cannot detect novel peptide sequences that have not been previously annotated or are rare. This study presents PowerNovo tool for de novo sequencing of proteins using tandem mass spectra acquired in a variety of types of mass analyzers and different fragmentation techniques. PowerNovo involves an ensemble of models for peptide sequencing: model for detecting regularities in tandem mass spectra, precursors, and fragment ions and a natural language processing model, which has a function of peptide sequence quality assessment and helps with reconstruction of noisy sequences. The results of testing showed that the performance of PowerNovo is comparable and even better than widely utilized PointNovo, DeepNovo, Casanovo, and Novor packages. Also, PowerNovo provides complete cycle of processing (pipeline) of mass spectrometry data and, along with predicting the peptide sequence, involves the peptide assembly and protein inference blocks.


Assuntos
Peptídeos , Análise de Sequência de Proteína , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Análise de Sequência de Proteína/métodos , Peptídeos/química , Peptídeos/análise , Sequência de Aminoácidos , Software , Proteômica/métodos , Algoritmos
9.
BMC Vet Res ; 20(1): 280, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951817

RESUMO

BACKGROUND: Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples. RESULTS: Out of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted. CONCLUSION: The presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.


Assuntos
Biomarcadores Tumorais , Doenças do Gato , Neoplasias Mamárias Animais , Espectrometria de Massas em Tandem , Animais , Feminino , Doenças do Gato/sangue , Doenças do Gato/patologia , Gatos , Espectrometria de Massas em Tandem/veterinária , Neoplasias Mamárias Animais/sangue , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/metabolismo , Biomarcadores Tumorais/sangue , Cromatografia Líquida/veterinária , Estudos Transversais , Metástase Neoplásica , Proteômica
10.
Sci Rep ; 14(1): 15216, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956138

RESUMO

Here, we present the whole genome sequence of Bt S2160-1, a potential alternative to the mosquitocidal model strain, Bti. One chromosome genome and four mega-plasmids were contained in Bt S2160-1, and 13 predicted genes encoding predicted insecticidal crystal proteins were identified clustered on one plasmid pS2160-1p2 containing two pathogenic islands (PAIs) designed as PAI-1 (Cry54Ba, Cry30Ea4, Cry69Aa-like, Cry50Ba2-like, Cry4Ca1-like, Cry30Ga2, Cry71Aa-like, Cry72Aa-like, Cry70Aa-like, Cyt1Da2-like and Vpb4C1-like) and PAI-2 (Cyt1Aa-like, and Tpp80Aa1-like). The clusters appear to represent mosquitocidal toxin islands similar to pathogenicity islands. Transcription/translation of 10 of the 13 predicted genes was confirmed by whole-proteome analysis using LTQ-Orbitrap LC-MS/MS. In summary, the present study identified the existence of a mosquitocidal toxin island in Bacillus thuringiensis, and provides important genomic information for understanding the insecticidal mechanism of B. thuringiensis.


Assuntos
Bacillus thuringiensis , Proteínas de Bactérias , Inseticidas , Proteômica , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Proteômica/métodos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Inseticidas/farmacologia , Sequenciamento Completo do Genoma/métodos , Genoma Bacteriano , Endotoxinas/genética , Toxinas de Bacillus thuringiensis , Ilhas Genômicas , Proteoma , Plasmídeos/genética , Espectrometria de Massas em Tandem , Animais , Proteínas Hemolisinas/genética
11.
Sci Rep ; 14(1): 15186, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956313

RESUMO

Influenza A virus subtype H1N1 can cause severe acute respiratory distress syndrome and death in young children and elderly individuals. H1N1 initiates inflammatory responses that aim to contain and eliminate microbial invaders. Various lipid mediators (LMs) are biosynthesized and play a critical role in fighting viruses during inflammation; thus, by profiling the LMs in patients, researchers can obtain mechanistic insights into diseases, such as the pathways disrupted. To date, the relationship between molecular alterations in LMs and the pathogenesis of H1N1 influenza in children is poorly understood. Here, we employed a targeted liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS) to profile LMs in serum from children with H1N1 influenza (H1N1 children) and recovered children. We found that 22 LM species were altered in H1N1 children with mild symptoms. Analysis of the LM profiles of recovered children revealed a decrease in the levels of thromboxane B2 (TxB2) and thromboxane B3 (TxB3) and an increase in the levels of other 8 altered LM species associated with H1N1 influenza, including cytochrome P450 (CYP) enzyme-derived dihydroxyeicosatrienoic acids (DiHETrEs) and hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA), and epoxyoctadecamonoenoic acids (EpOMEs) from linoleic acid (LA). Taken together, the results of this study revealed that serum LMs change dynamically in H1N1 children with mild symptoms. The dramatically altered LMs in H1N1 children could serve as a basis for potential therapeutics or adjuvants against H1N1 influenza.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Espectrometria de Massas em Tandem , Humanos , Influenza Humana/sangue , Influenza Humana/virologia , Criança , Masculino , Feminino , Pré-Escolar , Lipídeos/sangue , Cromatografia Líquida , Lactente , Lipidômica/métodos
12.
BMC Pediatr ; 24(1): 424, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956494

RESUMO

OBJECTIVES: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age. DESIGN AND METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach. RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates. CONCLUSION: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.


Assuntos
Biomarcadores , Teste em Amostras de Sangue Seco , Recém-Nascido Prematuro , Triagem Neonatal , Espectrometria de Massas em Tandem , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Valores de Referência , Masculino , Feminino , Biomarcadores/sangue , Recém-Nascido Prematuro/sangue , Estudos Retrospectivos , Teste em Amostras de Sangue Seco/métodos , China , Carnitina/sangue , Carnitina/análogos & derivados , Peso ao Nascer , População do Leste Asiático
13.
Rapid Commun Mass Spectrom ; 38(17): e9855, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38988294

RESUMO

RATIONALE: Rivaroxaban is an anticoagulant prescribed to patients who are at risk of medical conditions such as deep-vein thrombosis, pulmonary embolisms, and strokes caused by blood clots. The administration of this drug is monitored to adjust the dosage and evaluate patients' blood concentration. Rapid quantification of this drug in plasma could make it possible to ensure that the dose present in the blood of patients does not represent a danger for the medical intervention to be carried out. METHODS: Liquid chromatography-tandem mass spectrometry is usually employed to quantify rivaroxaban in blood, plasma, and serum. Here, an alternative method of analysis based on laser diode thermal desorption-triple quadrupole mass spectrometry (LDTD-QqQMS) was developed and comprehensively validated. This new method allows the quantification of rivaroxaban in less than 13 s from sample to sample. The extraction of rivaroxaban in human serum was done by a salting-out liquid-liquid extraction with acetonitrile and a saturated sodium chloride solution. RESULTS: The proposed method allows the quantification of rivaroxaban in less than 13 s from sample to sample. During validation, all criteria were respected. The accuracy was <15% of the nominal value, the precision was <15%CV, and the recovery was ≥89.9%. There were no observed carryover or matrix effects. Analysis of the extracted samples established the stability of dry (24 h) and wet samples (1 week) when samples cannot be analyzed immediately, a considerable advantage in a clinical setting. CONCLUSIONS: This method improves sample throughput by more than 1200% compared to liquid chromatography-tandem mass spectrometry methods of analysis of rivaroxaban and decreases analysis costs by reducing solvent consumption and instrument time.


Assuntos
Rivaroxabana , Espectrometria de Massas em Tandem , Rivaroxabana/sangue , Humanos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Limite de Detecção , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Modelos Lineares
14.
J Mass Spectrom ; 59(8): e5069, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38989730

RESUMO

Cinnamomi ramulus (CR) is a common Chinese herbal medicine with a long history. It is often used to treat exogenous wind-cold diseases in clinic, but its chemical compositions remain to be studied. In this study, CR was extracted with 75% ethanol, and UPLC-Q-Orbitrap-MS combined with data post-processing method was used to identify the chemical components in the extract. Through this technology, the components in CR can be separated and accurately identified. A total of 61 compounds were identified, including 14 simple phenylpropanoids, 3 coumarins, 5 lignans, 14 flavonoids, 10 benzoic acids, 8 organic acids, and 7 others. This study confirmed the existence of these compounds in CR and speculated the cleavage pathways of each compound, which enriched the mass spectrometry data and cleavage rules. This study can provide a reference for CR and other research.


Assuntos
Cumarínicos , Medicamentos de Ervas Chinesas , Flavonoides , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Cumarínicos/química , Cumarínicos/análise , Flavonoides/análise , Flavonoides/química , Lignanas/análise , Lignanas/química , Espectrometria de Massas/métodos , Cinnamomum/química , Espectrometria de Massas em Tandem/métodos
15.
J Mass Spectrom ; 59(8): e5070, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38989742

RESUMO

Recently, our group has shown that fentanyl and many of its analogues form prototropic isomers ("protomers") during electrospray ionization. These different protomers can be resolved using ion mobility spectrometry and annotated using mobility-aligned tandem mass spectrometry fragmentation. However, their formation and the extent to which experimental variables contribute to their relative ratio remain poorly understood. In the present study, we systematically investigated the effects of mixtures of common chromatographic solvents (water, methanol, and acetonitrile) and pH on the ratio of previously observed protomers for 23 fentanyl analogues. Interestingly, these ratios (N-piperidine protonation vs. secondary amine/O = protonation) decreased significantly for many analogues (e.g., despropionyl ortho-, meta-, and para-methyl fentanyl), increased significantly for others (e.g., cis-isofentanyl), and remained relatively constant for the others as solvent conditions changed from 100% organic solvent (methanol or acetonitrile) to 100% water. Interestingly, pH also had significant effects on this ratio, causing the change in ratio to switch in many cases. Lastly, increasing conditions to pH ≥ 4.0 also prompted the appearance of new mobility peaks for ortho- and para-methyl acetyl fentanyl, where all previous studies had only showed one single distribution. Because these ratios have promise to be used qualitatively for identification of these (and emerging) fentanyl analogues, understanding how various conditions (i.e., mobile phase selection and/or chromatographic gradient) affect their ratios is critically important to the development of advanced ion mobility and mass spectrometry methodologies to identify fentanyl analogues.


Assuntos
Fentanila , Espectrometria de Mobilidade Iônica , Solventes , Fentanila/análogos & derivados , Fentanila/química , Fentanila/análise , Solventes/química , Espectrometria de Mobilidade Iônica/métodos , Concentração de Íons de Hidrogênio , Espectrometria de Massas por Ionização por Electrospray/métodos , Isomerismo , Metanol/química , Acetonitrilas/química , Espectrometria de Massas em Tandem/métodos , Água/química
16.
J Mass Spectrom ; 59(8): e5075, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38989744

RESUMO

Prinsepia utilis Royle, native to the Himalayas, is esteemed in Chinese and Indian folk medicine for its diverse medicinal benefits, targeting arthritis, pain relief, bone disorders, and joint discomfort. This study examined the 25% aqueous methanol extract of P. utilis leaves using UPLC-Q-TOF-MS/MS, identifying 78 metabolites, 76 of which were reported for the first time in P. utilis. These included 64 phenolics represented by 56 flavonoids, 5 phenolic acids, 3 phenolic glycosides, 4 terpenoids, 2 lignan glycosides, and 8 other compounds, expanding the knowledge of its chemical composition. These findings lay a foundation for further research, providing insights into potential bioactive compounds and opening avenues for applications in natural product drug discovery, traditional medicine, and nutraceutical development, leveraging the plant's established traditional uses.


Assuntos
Flavonoides , Metabolômica , Extratos Vegetais , Folhas de Planta , Espectrometria de Massas em Tandem , Folhas de Planta/química , Folhas de Planta/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Flavonoides/análise , Fenóis/análise , Glicosídeos/análise , Glicosídeos/metabolismo , Metaboloma , Terpenos/análise , Terpenos/metabolismo , Lignanas/análise , Lignanas/metabolismo , Hidroxibenzoatos
17.
Environ Monit Assess ; 196(8): 725, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990243

RESUMO

UV filters and benzotriazole UV stabilizers are considered emerging contaminants in the environment. LC-MS/MS and GC-MS methods, involving a single solid phase extraction protocol, were developed and validated to determine eight UV filters and seven UV stabilizers, respectively in wastewater from a wastewater treatment plant (WWTP) in Lüneburg, Germany. The LC-MS/MS method exhibited extraction recoveries of ≥ 71% at six different fortification levels with limits of detection (LODs) range of 0.02 ng mL-1 - 0.09 ng mL-1. Extraction recoveries of 47 to 119% at six different fortification levels were obtained for the GC-MS method with LODs range of 0.01 - 0.09 ng mL-1. Among the UV filters, the highest mean concentration was determined for octocrylene (OCR) in influent (3.49 ng mL-1) while the highest mean concentration was measured for 2-hydroxy-4-octyloxybenzophenone (UV 531) in influent (0.44 ng mL-1) among the UV stabilizers. Potential risk to aquatic organisms was assessed by the risk quotient approach. Only OCR presented a high risk to aquatic invertebrates whereas 2-ethylhexyl 4-methoxycinnamate (EHMC) and 2-ethylhexyl salicylate (EHS) posed high risks to algae. Benzotriazole UV stabilizers presented negligible risks to aquatic invertebrates and fish. This work reports the detection of rarely studied 4-aminobenzoic acid (PABA) and UV 531 in WWTP influent and effluent. The occurrence and risk assessment of target benzotriazole UV stabilizers in wastewater from a German WWTP was demonstrated for the first time.


Assuntos
Monitoramento Ambiental , Protetores Solares , Triazóis , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Poluentes Químicos da Água/análise , Alemanha , Protetores Solares/análise , Triazóis/análise , Medição de Risco , Espectrometria de Massas em Tandem , Eliminação de Resíduos Líquidos/métodos , Cromatografia Gasosa-Espectrometria de Massas , Acrilatos/análise , Cromatografia Líquida
18.
CNS Neurosci Ther ; 30(7): e14827, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38992878

RESUMO

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.


Assuntos
Anticonvulsivantes , Epilepsia , Levetiracetam , Saliva , Humanos , Levetiracetam/farmacocinética , Levetiracetam/sangue , Feminino , Saliva/química , Saliva/metabolismo , Gravidez , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangue , Anticonvulsivantes/análise , Adulto , Epilepsia/tratamento farmacológico , Epilepsia/sangue , Adulto Jovem , Monitoramento de Medicamentos/métodos , Piracetam/análogos & derivados , Piracetam/análise , Piracetam/farmacocinética , Piracetam/sangue , Estudos Prospectivos , Estudos de Coortes , Espectrometria de Massas em Tandem/métodos
19.
Pharmacol Res Perspect ; 12(4): e1241, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38992911

RESUMO

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6ß-hydroxycortisol, deoxycholic acid, and 1ß-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM.


Assuntos
Biomarcadores , Citocromo P-450 CYP3A , Monitoramento de Medicamentos , Compostos de Fenilureia , Quinolinas , Humanos , Compostos de Fenilureia/urina , Compostos de Fenilureia/farmacocinética , Compostos de Fenilureia/sangue , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Feminino , Quinolinas/urina , Quinolinas/uso terapêutico , Quinolinas/sangue , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Idoso , Pessoa de Meia-Idade , Masculino , Biomarcadores/urina , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos/urina , Antineoplásicos/uso terapêutico , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Inibidores de Proteínas Quinases/urina , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/sangue , Neoplasias/urina , Espectrometria de Massas em Tandem/métodos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/urina , Neoplasias do Endométrio/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/urina , Cromatografia Líquida/métodos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/urina , Neoplasias da Glândula Tireoide/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/urina , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/urina , Carcinoma de Células Renais/sangue
20.
Ren Fail ; 46(2): 2375033, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967135

RESUMO

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.


Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Flavonas , Rim , Panax notoginseng , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica , Transdução de Sinais , Animais , Camundongos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Panax notoginseng/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Rim/patologia , Rim/efeitos dos fármacos , Astrágalo/química , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão
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