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1.
Int J Mol Sci ; 24(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37511236

RESUMO

Rectal cancer (RC) is a gastrointestinal cancer with a poor prognosis. While some studies have shown metabolic reprogramming to be linked to RC development, it is difficult to define biomolecules, like lipids, that help to understand cancer progression and response to therapy. The present study investigated the relative lipid abundance in tumoral tissue associated with neoadjuvant therapy response using untargeted liquid chromatography-mass spectrometry lipidomics. Locally advanced rectal cancer (LARC) patients (n = 13), clinically staged as T3-4 were biopsied before neoadjuvant chemoradiotherapy (nCRT). Tissue samples collected before nCRT (staging) and afterwards (restaging) were analyzed to discover lipidomic differences in RC cancerous tissue from Responders (n = 7) and Non-responders (n = 6) to nCRT. The limma method was used to test differences between groups and to select relevant feature lipids from tissue samples. Simple glycosphingolipids and differences in some residues of glycerophospholipids were more abundant in the Non-responder group before and after nCRT. Oxidized glycerophospholipids were more abundant in samples of Non-responders, especially those collected after nCRT. This work identified potential lipids in tissue samples that take part in, or may explain, nCRT failure. These results could potentially provide a lipid-based explanation for nCRT response and also help in understanding the molecular basis of RC and nCRT effects on the tissue matrix.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Lipidômica , Quimiorradioterapia , Neoplasias Retais/metabolismo , Lipídeos , Resultado do Tratamento
2.
Am J Reprod Immunol ; 89(3): e13673, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36585861

RESUMO

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.


Assuntos
Aborto Habitual , Ácidos Graxos Ômega-3 , Humanos , Feminino , Gravidez , Fosfolipídeos , Aborto Habitual/terapia , Aborto Habitual/etiologia , Ácidos Graxos Ômega-3/uso terapêutico , Emulsões Gordurosas Intravenosas , Cromatografia Líquida
3.
Biology (Basel) ; 11(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36552244

RESUMO

The main aim of this study was to compare the performance over different distances, the critical velocity (CV), and plasma acylcarnitines/amino acids of male and female adolescent swimmers. Moreover, we applied the complex network approach to identify which molecules are associated with athletes' performances. On the first day under a controlled environment, blood samples were collected after 12 h of overnight fasting. Performance trials (100, 200, 400, and 800-m) were randomly performed in the subsequent four days in a swimming pool, and CV was determined by linear distance versus time mathematical function. Metabolomic analyses were carried out on a triple quadrupole mass spectrometer performing electrospray ionization in the positive ionization mode. No difference was observed between the performance of male and female swimmers. Except for 200-m distance (p = 0.08), plasma tyrosine was positively and significantly associated with the female times during the trials (100-m, p = 0.04; 400-m, p = 0.04; 800-m, p = 0.02), and inversely associated with the CV (p = 0.02). The complex network approach showed that glycine (0.406), glutamine (0.400), arginine (0.335), free carnitine (0.355), tryptophan (0.289), and histidine (0.271) were the most influential nodes to reach tyrosine. These results revealed a thread that must be explored in further randomized/controlled designs, improving the knowledge surrounding nutrition and the performance of adolescent swimmers.

4.
Metabolites ; 12(11)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36355139

RESUMO

The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection-tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines. We adapted a method that is widely used for newborn screening tests on dried blood for urine samples in order to detect metabolites related to COVID-19 infection. We analyzed samples from 246 volunteers with diagnostic confirmation via PCR. Urine samples were self-collected, diluted, and analyzed with a run time of 4 min. A Lasso statistical classifier was built using 75/25% data for training/validation sets and achieved high diagnostic performances: 97/90% sensitivity, 95/100% specificity, and 95/97.2% accuracy. Additionally, we predicted on two withheld sets composed of suspected hospitalized/symptomatic COVID-19-PCR negative patients and patients out of the optimal time-frame collection for PCR diagnosis, with promising results. Altogether, we show that the benchmarked FIA-MS/MS method is promising for COVID-19 screening and diagnosis, and is also potentially useful after the peak viral load has passed.

5.
Biomed Chromatogr ; 35(9): e5147, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33885176

RESUMO

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC-MS/MS for rivaroxaban quantification in human plasma using an one-step liquid-liquid extraction. The linear concentration range was 1-600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.


Assuntos
Cromatografia Líquida/métodos , Rivaroxabana/sangue , Rivaroxabana/farmacocinética , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Humanos , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Rivaroxabana/química , Rivaroxabana/isolamento & purificação , Adulto Jovem
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