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1.
Nat Immunol ; 19(8): 809-820, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29967452

RESUMO

Regulatory factor X 7 (Rfx7) is an uncharacterized transcription factor belonging to a family involved in ciliogenesis and immunity. Here, we found that deletion of Rfx7 leads to a decrease in natural killer (NK) cell maintenance and immunity in vivo. Genomic approaches showed that Rfx7 coordinated a transcriptional network controlling cell metabolism. Rfx7-/- NK lymphocytes presented increased size, granularity, proliferation, and energetic state, whereas genetic reduction of mTOR activity mitigated those defects. Notably, Rfx7-deficient NK lymphocytes were rescued by interleukin 15 through engagement of the Janus kinase (Jak) pathway, thus revealing the importance of this signaling for maintenance of such spontaneously activated NK cells. Rfx7 therefore emerges as a novel transcriptional regulator of NK cell homeostasis and metabolic quiescence.


Assuntos
Interleucina-15/metabolismo , Células Matadoras Naturais/metabolismo , Fator Regulador X1/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Quimera , Metabolismo Energético , Redes Reguladoras de Genes , Imunidade Celular/genética , Imunidade Inata/genética , Janus Quinases/metabolismo , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator Regulador X1/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
2.
EMBO J ; 32(4): 566-82, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23376921

RESUMO

Selective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We show that the human transmembrane protein TMEM59 contains a minimal 19-amino-acid peptide in its intracellular domain that promotes LC3 labelling and lysosomal targeting of its own endosomal compartment. Interestingly, this peptide defines a novel protein motif that mediates interaction with the WD-repeat domain of ATG16L1, thus providing a mechanistic basis for the activity. The motif is represented with the same ATG16L1-binding ability in other molecules, suggesting a more general relevance. We propose that this motif may play an important role in targeting specific membranous compartments for autophagic degradation, and therefore it may facilitate the search for adaptor proteins that promote selective autophagy by engaging ATG16L1. Endogenous TMEM59 interacts with ATG16L1 and mediates autophagy in response to Staphylococcus aureus infection.


Assuntos
Autofagia , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteólise , Motivos de Aminoácidos , Proteínas Relacionadas à Autofagia , Proteínas de Transporte/genética , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/metabolismo
3.
Rapid Commun Mass Spectrom ; 30(20): 2228-36, 2016 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-27472302

RESUMO

RATIONALE: Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. METHODS: Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. RESULTS: In the CID-MS/MS spectra of [M+H](+) ions of XH1, XH2 and XH4 the product ions formed due to H2 O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2 O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64 Da (concomitant loss of two molecules of H2 O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. CONCLUSIONS: A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Xantonas/química , Estrutura Molecular , Transição de Fase , Espectrometria de Massas por Ionização por Electrospray
4.
Cureus ; 16(1): e52590, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38371149

RESUMO

Ranula is a benign cystic lesion caused by the escape and collection of salivary mucus. Classically, it is divided into simple ranulas, a cystic mass in the floor of the mouth, and diving/plunging/cervical ranulas, a submandibular mass without apparent intraoral involvement. Although plunging ranula is a well-documented cause of neck swelling, its association with the presence of ectopic sublingual glands is extremely rare, with less than five cases reported. Other cervical cystic lesions may have the same clinical aspect; therefore, advanced diagnostic techniques like a CT scan or MRI play a critical role in early diagnosis. Different approaches have been used to treat ranulas, including non-invasive, minimally invasive, and surgical techniques. The purpose of this paper is to highlight a case report of a giant plunging ranula due to an anatomical aberration of the right sublingual gland, along with a significant literature review.

5.
Rapid Commun Mass Spectrom ; 27(12): 1303-10, 2013 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-23681807

RESUMO

RATIONALE: Several methylenedioxy chalcones, flavanones and flavones substituted with mono-, di- and trimethoxy groups have been used in the treatment of proliferative conditions like cancer and inflammatory diseases. The application of these flavonoids in biology requires an analytical method to ensure a detailed knowledge of their structures after drug metabolism. METHODS: Electrospray ionization mass (ESI-MS) and tandem mass (ESI-MS/MS) spectra were acquired using a Q-TOF 2 instrument. Fragmentation patterns and their pathways were analyzed by CID-MS(2-3) spectra acquired in a LXQ linear ion trap mass spectrometer using standard isolation and excitation procedures (activation q value of 0.25, activation time of 30 ms). ESI-MS and ESI-MS(n) conditions: spray voltage 5 kV, nitrogen 8.00 sheath gas flow rate (arb), heated capillary temperature 275°C, capillary voltage 10.99 V; tube lens voltage 75.01 V. RESULTS: The ESI-MS/MS spectra of chalcones were nearly identical to their corresponding isomeric flavanones with (0,α)A(+)/(1,3)A(+) and (0,1')B(+)/(1,4)B(+) cleavages. Other common losses are of (•)CH3, H2O, HCHO and C2H2O. The characteristic loss of C2H2O and absence of a (0,α)B(+)/(1,3)B(+) product ion allows to distinguish between the 2- or 4-methoxy-substituted chalcones and flavanones. Common losses of (•)CH3, (•)CH3 and (•)H, and C2H2O2 characteristic for the presence of methylenedioxy groups were observed in flavones. CONCLUSIONS: The substitution pattern on the B-ring leads to distinct base peak formation in the flavones. In addition, differentiation of isomers with methoxy substituents in ortho and para positions of the B-ring was achieved using MS/MS in chalcones and flavanones. This method will be helpful for identification of these compounds in biological mixtures.


Assuntos
Chalconas/análise , Flavanonas/análise , Flavonas/análise , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos
6.
Hemoglobin ; 37(2): 183-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23368878

RESUMO

Hb Plasencia is a thalassemic hemoglobin (Hb) mutation caused by a leucine to arginine replacement at residue 125 of the α2-globin chain (HBA2:c.377T>G). This variant was first described in the heterozygous state in association with a very mild α-thalassemic phenotype in three members of a Spanish family from Plasencia, Western Spain. Reviewing the molecular characterization of 308 Portuguese individual suspected of having α-thalassemia (α-thal) we found Hb Plasencia to be the second most frequent mutation after the -α(3.7) deletion.


Assuntos
Hemoglobinas Anormais/genética , Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Testes Genéticos , Humanos , Reação em Cadeia da Polimerase , Portugal , Talassemia alfa/diagnóstico
7.
Cureus ; 15(1): e33313, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36741627

RESUMO

Hurler syndrome (HS) belongs to the category of mucopolysaccharidosis (MPS), a spectrum of rare genetic disorders of the mucopolysaccharides metabolism. This syndrome is due to a defect in α-iduronidase, an enzyme responsible for the degradation of the glycosaminoglycans (GAGs) heparin and dermatan sulfate. Intra and extracellular accumulation of these non-metabolized substances may lead to multisystemic dysfunction, with severe stomatognathic involvement that may often need treatment. The aim of this article is to present the heterogeneity of orofacial and radiographic findings observed in two patients with HS with long-term follow-up, who were referred to our Stomatology department.

8.
Cureus ; 14(8): e27874, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36110449

RESUMO

Lesch-Nyhan syndrome (LNS) is an inherited recessive X-related disorder caused by a deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase. It is characterized by dystonia and compulsive self-mutilation, in particular, biting behavior on the oral mucosa, tongue, lips, fingers, and shoulders, typically before one year of age. The majority of these patients require several procedures, including dental extractions, to prevent significant secondary lesions. This article aims to report a clinical case of a 12-year-old boy with an LNS diagnosis who was referred to the Paediatric Stomatology Department of Central Lisbon University Hospital. Since the age of eight, the patient had displayed self-harm behavior, with arm and oral injuries. On evaluation, he presented with deep ulcerated lesions on the lips and tongue, with substance loss associated with a significant decrease in food intake and consequent weight loss. The management included conservative therapy with gabapentin, lorazepam, and botulinum toxin injections. A successful reduction of self-mutilation with no signs of new lesions in the oral cavity and an improvement in nutritional status were reported. The therapeutic approach is essential to provide the best quality of life for patients and their caregivers. To delay radical treatments, multiple therapeutic options can be used. The oral pathology team considered that the most appropriate therapy was botulinum toxin A injections along with therapeutic adjustment, which was effective in wound healing and self-mutilation behavior ceasing at the two-month follow-up.

9.
J Am Soc Mass Spectrom ; 33(5): 793-802, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35438496

RESUMO

Cholesteryl esters (CE) are prone to oxidation under increased oxidative stress conditions, but little is known about oxidized CE species (oxCE). To date, only a few oxCE have been identified, however, mainly based on the detection of molecular ions by mass spectrometry (MS) or target approaches for specific oxCE. The study of oxCE occurring from radical oxidation is still scarcely addressed. In this work, we made a comprehensive assessment of oxCE derivatives and their specific fragmentation patterns to identify detailed structural features and isomer differentiation using high-resolution C18 HPLC-MS- and MS/MS-based lipidomic approaches. The LC-MS/MS analysis allowed us to pinpoint oxCE structural isomers of long-chain and short-chain species, eluting at different retention times (tR). Data analysis revealed that oxCE can be modified either in the fatty acyl moiety or in the cholesterol ring. The location of the hydroxy/hydroperoxy group originates characteristic fragment ions, namely the unmodified cholestenyl cation (m/z 369) for the isomer with oxidation in the fatty acyl chain or ions at m/z 367 and m/z 385 (369 + 16) when oxygenation occurs in the cholesterol ring. Additionally, we identified CE 18:2 and 20:4 aldehydic and carboxylic short-chain products that showed a clear fragmentation pattern that confirmed the modification in the fatty acyl chain. Specific fragmentation fingerprinting allowed discrimination of the isobaric short-chain species, namely carboxylic short-chain products, from hydroxy aldehyde short-chain products, with a hydroxycholesterol moiety. This new information is important to identify different oxCE in biological samples and will contribute to unraveling their role in biological conditions and diseases such as cardiovascular disease.


Assuntos
Ésteres do Colesterol , Espectrometria de Massas em Tandem , Aldeídos , Ésteres do Colesterol/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida/métodos , Oxirredução , Espectrometria de Massas em Tandem/métodos
10.
Food Chem X ; 16: 100468, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36281231

RESUMO

The accumulation of advanced glycation end-products (AGEs) in the body is implicated in numerous diseases, being methylglyoxal (MGO) one of the main precursors. One of the strategies to reduce AGEs accumulation might be acting in an early stage of glycation by trapping MGO. Thus, this work aimed to evaluate, for the first time, the potential of elderberries polyphenols to trap MGO, access the formation of MGO adducts, and evaluate the cytoprotection effect in HepG2 and Caco-2 cells. The results demonstrated that monoglycosylated anthocyanins (cyanidin-3-glucoside and cyanidin-3-sambubioside) are very efficient in trapping MGO, forming mono- and di-adducts. Quercetin-3-glucoside and quercetin-3-rutinoside reacted slowly, while diglycosylated anthocyanins did not react. The trapping of MGO by elderberry monoglycosylated anthocyanins significantly decreased the MGO cytotoxicity in HepG2 cells (∼70 % of cell viability), while the effect in Caco-2 cells was lower (∼50 %). Thus, elderberry phenolics present antiglycation potential by trapping MGO.

11.
Sci Rep ; 12(1): 12226, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35851408

RESUMO

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils' counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.


Assuntos
Esofagite Eosinofílica , Refluxo Gastroesofágico , Criança , Cromatografia Líquida , Enterite , Proteína Catiônica de Eosinófilo , Eosinofilia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/patologia , Eosinófilos/metabolismo , Gastrite , Refluxo Gastroesofágico/complicações , Humanos , Ligantes , Muco/metabolismo , Peptídeos , Proteômica , Espectrometria de Massas em Tandem
12.
Rapid Commun Mass Spectrom ; 25(20): 3185-95, 2011 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-21953975

RESUMO

Cinnamylideneacetophenones have been extensively used as versatile starting materials in numerous different transformations. The structural characterization of this type of compounds is, therefore, of crucial importance since it can give information on the chemistry, reactivity and also the potential biological activity of this type of compounds. Thus, 24 derivatives were systematically studied by tandem mass spectrometry (MS(2)) with electrospray ionization (ESI), in positive ion mode. The protonated molecules, [M + H](+), formed under ESI conditions were induced to dissociate and the fragmentation patterns were studied. The information collected provided important structural information on the type of substituents present and constitute an important database concerning this family of compounds. Overall, it was found that the substitution pattern of the cinnamylideneacetophenone derivatives changes the ESI-MS(2) fragmentation considerably. These results indicate that ESI-MS(2) is a useful technique for distinguishing positional isomers of these cinnamylideneacetophenone derivatives.

13.
J Agric Food Chem ; 69(11): 3466-3478, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33721493

RESUMO

Frying allows cooking food while promoting their organoleptic properties, imparting crunchiness and flavor. The drawback is the oxidation of triacylglycerides (TAGs), leading to the formation of primary oxidized TAGs. Although they have been associated with chronic and degenerative diseases, they are precursors of pleasant flavors in fried foods. Nevertheless, there is a lack of knowledge about the oxidation species present in foods and their involvement in positive/negative health effects. In this work, high-resolution (HR) C30 reversed-phase (RP)-liquid chromatography (LC)-tandem HR mass spectrometry (MS/MS) was used to identify primary oxidation TAGs resulting from heating triolein (160 °C, 5 min). This allows simulating the initial heating process of frying oils usually used to prepare fried foods, such as chips, crisps, and snacks. Beyond hydroxy, dihydroxy, hydroperoxy, and hydroxy-hydroperoxy derivatives, already reported in phospholipids oxidized by Fenton reaction, new compounds were identified, such as dihydroxy-hydroperoxy-triolein derivatives and positional isomers (9/10- and 9/12-dihydroxy-triolein derivatives). These compounds should be considered when proposing flavor formation pathways and/or mitigating lipid-derived reactive oxygen species occurring during food frying.


Assuntos
Espectrometria de Massas em Tandem , Trioleína , Culinária , Temperatura Alta , Oxirredução , Temperatura
15.
Anal Bioanal Chem ; 396(2): 887-97, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19902191

RESUMO

In this study, an ethanolic extract from Portuguese propolis was prepared, fractionated by high-performance liquid chromatography, and the identification of the phenolic compounds was done by electrospray mass spectrometry in the negative mode. This technical approach allowed the identification of 37 phenolic compounds, which included not only the typical phenolic acids and flavonoids found in propolis from temperate zones but also several compounds in which its occurrence have never been referred to in the literature. Four of the novel phenolic compounds were methylated and/or esterified or hydroxylated derivatives of common poplar flavonoids, although six peculiar derivatives of pinocembrin/pinobanksin, containing a phenylpropanoic acid derivative moiety in their structure, were also identified. Furthermore, the Portuguese propolis sample was shown to contain a p-coumaric ester derivative dimer.


Assuntos
Fenóis/análise , Extratos Vegetais/análise , Própole/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Portugal , Espectrometria de Massas por Ionização por Electrospray
16.
Eur J Mass Spectrom (Chichester) ; 15(5): 605-16, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19679941

RESUMO

Isomeric 2'-hydroxychalcones bearing nitro and methoxy groups in different positions of their skeleton were analyzed by tandem mass spectrometry (MS/MS) with electrospray ionization (ESI), in positive mode. Collision-induced dissociation of the protonated molecules, [M + H](+), formed under electrospray conditions were studied and it was found that the product ion spectra of these chalcones presented different fragmentation patterns depending on the position of the substituents on the molecule. The product ion spectra (ESI- MS/MS) of the B ring ortho-nitro substituted 2'-hydroxychalcone and of the 4'-methoxychalcones showed loss of OH, 2OH and combined losses of OH and H(2)O. These fragment ions were absent in the spectra of the respective meta- and para isomers. The observed differences in the product ion spectra of these nitrochalcones allowed identification of the o-nitro derivatives. Distinction between the meta- and para derivatives was not achieved. Chalcones bearing 6'-methoxy substituents showed distinct fragmentation from the one observed for their isomers, 4'-methoxychalcones, since they present only one fragment ion, a typical ((0,alpha)A - H)(+) and, therefore, do not allow detailed structural information to be obtained, nor to differentiate between the o-, m- or p-nitro isomers. Overall, it was found that small changes in the substitution pattern of chalcones change their fragmentation considerably in the ESI-MS/MS, and that these features permit the differentiation of specific isomers of these 2'-hydroxynitrochalcones.

17.
J Pediatr (Rio J) ; 94(6): 642-651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29112859

RESUMO

OBJECTIVES: To translate and culturally adapt the Pediatric Eosinophilic Esophagitis Symptom Score (version 2.0), a tool used to assess pediatric eosinophilic esophagitis symptoms reported by patients and/or their parents/caregivers. METHODS: The Pediatric Eosinophilic Esophagitis Symptom Score was translated through the following stages: initial translation, back-translation, and consensus of independent reviewers through the Delphi technique. The pre-final version of the Pediatric Eosinophilic Esophagitis Symptom Score was applied to five 8-to-18-year-old patients and to ten parents of two-to-18-year-old patients from an outpatient pediatric gastroenterology service (pre-test). RESULTS: During the translation process, no translations presenting with difficult consensus in the review process or grammar inconsistencies were observed. During the pre-test, difficulties in comprehension of some unconventional terms, e.g., "náusea", were observed. Adverbs of frequency, such as "quase nunca" were also identified as being of difficult understanding by patients and parents, and the substitution by the term "raramente" was suggested. Such difficulties may be inherent to the pediatric age group. Age 8 years or above should be considered adequate for the self-reporting of symptoms. CONCLUSIONS: The study presents the Brazilian version of the Pediatric Eosinophilic Esophagitis Symptom Score, which is adapted to the Brazilian culture. This version may be introduced as a clinical and research tool for the assessment of patients with esophagic disease symptoms. The Pediatric Eosinophilic Esophagitis Symptom Score is a breakthrough in the evaluation of symptoms of pediatric eosinophilic esophagitis, since it reinforces the importance of self-reporting by patients who experience this disease.


Assuntos
Esofagite Eosinofílica/diagnóstico , Autorrelato/normas , Traduções , Adolescente , Brasil , Cuidadores , Criança , Pré-Escolar , Comparação Transcultural , Feminino , Humanos , Masculino , Pais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
J Pharm Biomed Anal ; 151: 227-234, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29367160

RESUMO

Collision induced dissociation of triple quadrupole mass spectrometer (CID-QqQ) and high-energy collision dissociation (HCD) of Orbitrap were compared for four neuropeptides Y Y1 (NPY Y1) receptor antagonists and showed similar qualitative fragmentation and structural information. Orbitrap high resolution and high mass accuracy HCD fragmentation spectra allowed unambiguous identification of product ions in the range 0.04-4.25 ppm. Orbitrap mass spectrometry showed abundant analyte-specific product ions also observed on CID-QqQ. These results show the suitability of these product ions for use in quantitative analysis by MRM mode. In addition, it was found that all compounds could be determined at levels >1 µg L-1 using the QqQ instrument and that the detection limits for this analyzer ranged from 0.02 to 0.6 µg L-1. Overall, the results obtained from experiments acquired in QqQ show a good agreement with those acquired from the Orbitrap instrument allowing the use of this relatively inexpensive technique (QqQ) for accurate quantification of these compounds in clinical and academic applications.


Assuntos
Arginina/análogos & derivados , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Espectrometria de Massas em Tandem/métodos , Arginina/análise , Arginina/química , Limite de Detecção , Espectrometria de Massas em Tandem/economia , Espectrometria de Massas em Tandem/instrumentação
19.
Cell Rep ; 23(1): 39-49, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29617671

RESUMO

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8+ T lymphocytes expanded moderately better but were less polyfunctional than control cells. Mice with Shp-2-deficient T cells also showed no significant improvement in controlling immunogenic tumors and responded similarly to controls to α-PD-1 treatment. We therefore showed that Shp-2 is dispensable in T cells for globally establishing exhaustion and for PD-1 signaling in vivo. These results reveal the existence of redundant mechanisms downstream of inhibitory receptors and represent the foundation for defining these relevant molecular events.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Neoplasias Experimentais/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Transdução de Sinais , Viroses/imunologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/imunologia
20.
J Am Soc Mass Spectrom ; 18(2): 218-25, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17070697

RESUMO

Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) have been used to differentiate the 2- and 4-methylpyridyl isomers of free-base and metallated cationic beta-vinylpyridylporphyrins. The analysis by ESI-MS/MS of the deuterated analogs and semiempirical calculations of structural and electronic parameters were also undertaken. The two free-base isomers are easily differentiated by ESI-MS/MS but the presence of a metallic center renders differentiation of the metallated isomers less effective. The data acquired show that of all the studied compounds, the free-base 2-methylpyridyl isomer, which was operative in the in vitro photoinactivation of Herpes simples virus, has a different gas-phase behavior. Local distortion of the macrocycle due to the presence of the beta-vinylpyridyl substituent occurs for all the compounds, but a different electron density distribution can account for the observed gas-phase behavior of this potential virus photoinactivator.


Assuntos
Antivirais/química , Porfirinas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Compostos de Vinila/química , Antivirais/análise , Cátions/química , Isomerismo , Fotoquímica , Porfirinas/análise , Compostos de Vinila/análise , Inativação de Vírus
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