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1.
Nanotechnology ; 35(15)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38150723

RESUMO

Smart energy storage systems, such as electrochromic supercapacitor (ECSC) integrated technology, have drawn a lot of attention recently, and numerous developments have been made owing to their reliable performance. Developing novel electrode materials for ECSCs that embed two different technologies in a material is an exciting and emerging field of research. To date, the research into ECSC electrode materials has been ongoing with excellent efforts, which need to be systematically reviewed so that they can be used to develop more efficient ECSCs. This mini-review provides a general composition, main evaluation parameters and future perspectives for electrode materials of ECSCs as well as a brief overview of the published reports on ECSCs and performance statistics on the existing literature in this field.

2.
Am J Physiol Cell Physiol ; 325(1): C69-C78, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37212547

RESUMO

Cardiac calcification is a crucial but underrecognized pathological process, greatly increasing the risk of cardiovascular diseases. Little is known about how cardiac fibroblasts, as a central mediator, facilitate abnormal mineralization. Erythropoietin-producing hepatoma interactor B2 (EphrinB2), previously identified as an angiogenic regulator, is involved in fibroblast activation, while its role in the osteogenic differentiation of cardiac fibroblasts is unknown. Bioinformatics analysis was conducted to characterize the expression of the Ephrin family in human calcified aortic valves and calcific mouse hearts. The effects of EphrinB2 on cardiac fibroblasts to adopt osteogenic fate was determined by gain- and loss-of-function. EphrinB2 mRNA level was downregulated in calcified aortic valves and mouse hearts. Knockdown of EphrinB2 attenuated mineral deposits in adult cardiac fibroblasts, whereas overexpression of EphrinB2 promoted their osteogenic differentiation. RNA sequencing data implied that Ca2+-related S100/receptor for advanced glycation end products (RAGE) signaling may mediate EphrinB2-induced mineralization in cardiac fibroblasts. Moreover, L-type calcium channel blockers inhibited osteogenic differentiation of cardiac fibroblasts, implying a critical role in Ca2+ influx. In conclusion, our data illustrated an unrecognized role of EphrinB2, which functions as a novel osteogenic regulator in the heart through Ca2+ signaling and could be a potential therapeutic target in cardiovascular calcification.NEW & NOTEWORTHY In this study, we observed that adult cardiac fibroblasts but not neonatal cardiac fibroblasts exhibit the ability of osteogenic differentiation. EphrinB2 promoted osteogenic differentiation of cardiac fibroblasts through activating Ca2+-related S100/RAGE signaling. Inhibition of Ca2+ influx using L-type calcium channel blockers inhibited EphrinB2-mediated calcification of cardiac fibroblasts. Our data implied an unrecognized role of EphrinB2 in regulating cardiac calcification though Ca2+-related signaling, suggesting a potential therapeutic target of cardiovascular calcification.


Assuntos
Carcinoma Hepatocelular , Eritropoetina , Neoplasias Hepáticas , Adulto , Animais , Humanos , Camundongos , Cálcio , Bloqueadores dos Canais de Cálcio/farmacologia , Diferenciação Celular , Eritropoetina/farmacologia , Fibroblastos , Osteogênese/fisiologia , Receptor para Produtos Finais de Glicação Avançada
3.
Eur Radiol ; 33(1): 656-665, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35852578

RESUMO

OBJECTIVES: The current understanding of cerebral waste clearance (CWC) involves cerebrospinal fluid (CSF) participation but lacks convincing evidence for the direct participation of the parenchymal vascular system. The objective of this study was to evaluate the role of the parenchymal vascular system in CSF tracer clearance in rats. METHODS: We used superparamagnetic iron oxide-enhanced susceptibility-weighted imaging (SPIO-SWI) and quantitative susceptibility mapping (QSM) methods to simultaneously study 7 T MRI signal changes in parenchymal veins, arteries, and their corresponding para-vascular spaces in 26 rats, following intra-cisterna magna (ICM) infusion of different CSF tracers (FeREX, Ferumoxytol, Fe-Dextran) to determine the amount of tracer in the artery and vein quantitatively. RESULTS: We observed that the parenchymal venous system participated in CSF tracer clearance following ICM infusion of different MRI tracers with different concentrations of iron. Parenchymal venous participation was more obvious when 75 µg iron was injected. In the parenchymal veins, the relative mean (± SE) value of the susceptibility increased by 13.5 (± 1.0)% at 15 min post-tracer infusion (p < 0.01), and 33.6 (± 6.7)% at 45 min post-tracer infusion (p = 0.01), compared to baseline. In contrast to the parenchymal veins, a negligible amount of CSF tracer entered the parenchymal arteries: 1.3 (± 2.6)% at 15 min post-tracer infusion (p = 0.6), and 12 (± 19)% at 45 min post-tracer infusion (p = 0.5), compared to baseline. CONCLUSIONS: MRI tracers can enter the parenchymal vascular system and more MRI tracers were observed in the cerebral venous than arterial vessels, suggesting the direct participation of parenchymal vascular system in CWC. KEY POINTS: • MRI results revealed that the parenchymal venous system directly participates in cerebrospinal fluid tracer clearance following ICM infusion of MRI tracer. • Different sizes of MRI tracers can enter the parenchymal venous system.


Assuntos
Óxido Ferroso-Férrico , Imageamento por Ressonância Magnética , Animais , Ratos , Imageamento por Ressonância Magnética/métodos , Ferro , Líquido Cefalorraquidiano/diagnóstico por imagem
4.
Proc Natl Acad Sci U S A ; 116(13): 6298-6307, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30846549

RESUMO

Natural regulatory T cells (nTregs) ensure the control of self-tolerance and are currently used in clinical trials to alleviate autoimmune diseases and graft-versus-host disease after hematopoietic stem cell transfer. Based on CD39/CD26 markers, blood nTreg analysis revealed the presence of five different cell subsets, each representing a distinct stage of maturation. Ex vivo added microenvironmental factors, including IL-2, TGFß, and PGE2, direct the conversion from naive precursor to immature memory and finally from immature to mature memory cells, the latest being a no-return stage. Phenotypic and genetic characteristics of the subsets illustrate the structural parental maturation between subsets, which further correlates with the expression of regulatory factors. Regarding nTreg functional plasticity, both maturation stage and microenvironmental cytokines condition nTreg activities, which include blockade of autoreactive immune cells by cell-cell contact, Th17 and IL-10 Tr1-like activities, or activation of TCR-stimulating dendritic cell tolerization. Importantly, blood nTreg CD39/CD26 profile remained constant over a 2-y period in healthy persons but varied from person to person. Preliminary data on patients with autoimmune diseases or acute myelogenous leukemia illustrate the potential use of the nTreg CD39/CD26 profile as a blood biomarker to monitor chronic inflammatory diseases. Finally, we confirmed that naive conventional CD4 T cells, TCR-stimulated under a tolerogenic conditioned medium, could be ex vivo reprogrammed to FOXP3 lineage Tregs, and further found that these cells were exclusively committed to suppressive function under all microenvironmental contexts.


Assuntos
Microambiente Celular/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/fisiologia , Apirase/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Dinoprostona/metabolismo , Dipeptidil Peptidase 4/sangue , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Leucemia Mieloide , Células Th17/imunologia , Fator de Crescimento Transformador beta/metabolismo
5.
J Interv Cardiol ; 2021: 9934535, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34035674

RESUMO

INTRODUCTION: This network meta-analysis aimed to evaluate the efficacy and safety of different dual antiplatelet therapies (DAPTs) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). METHODS: Randomized controlled trials (RCTs) comparing longer-term (>12 months) DAPT (L-DAPT), 12-month DAPT (DAPT 12Mo), 6-month DAPT (DAPT 6Mo), 3-month DAPT followed by aspirin monotherapy (DAPT 3Mo + ASA), 3-month DAPT followed by a P2Y12 receptor inhibitor monotherapy (DAPT 3Mo + P2Y12), or 1-month DAPT with a P2Y12 receptor inhibitor monotherapy (DAPT 1Mo + P2Y12) were searched. Primary endpoints were all-cause mortality, cardiac death, myocardial infarction (MI), major bleeding, any bleeding, definite or probable stent thrombosis (ST), and net adverse clinical events (NACE). This Bayesian network meta-analysis was performed with the random-effects model. RESULTS: Twenty-four RCTs (n = 81339) were included. In comparison with L-DAPT, DAPT 6Mo (OR: 0.50, 95% CI: 0.29-0.83), DAPT 3Mo + P2Y12 (OR: 0.38, 95% CI: 0.18-0.82), DAPT 3Mo + ASA (OR: 0.44, 95% CI: 0.17-0.98), and DAPT 1Mo + P2Y12 (OR: 0.45, 95% CI: 0.14-0.93) were associated with a lower risk of major bleeding. DAPT 3Mo + P2Y12 (OR: 0.58, 95% CI: 0.38-0.88) reduced the risk of any bleeding when compared with DAPT 12Mo. L-DAPT decreased the risk of MI and definite or probable stent ST when compared with DAPT 6Mo. DAPT 3Mo + P2Y12 decreased the risk of NACE in comparison with DAPT 6Mo and DAPT 12Mo. No significant difference in all-cause mortality and cardiac death was observed. In patients with acute coronary syndrome, DAPT 6Mo was comparable to DAPT 12Mo. CONCLUSION: Short-term (1-3 months) DAPT is noninferior to DAPT 6Mo after DESs implantation, while L-DAPT reduces MI and definite or probable ST rates. DAPT 3Mo + P2Y12 might be a reasonable trade-off in patients with high risk of bleeding accompanied by ischemia.


Assuntos
Reestenose Coronária/prevenção & controle , Quimioterapia Combinada , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/farmacologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Metanálise em Rede , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Risco Ajustado/métodos
6.
BMC Endocr Disord ; 21(1): 78, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882907

RESUMO

BACKGROUND: Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. CASE PRESENTATION: A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. CONCLUSIONS: She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.


Assuntos
Diabetes Insípido Nefrogênico/congênito , Diabetes Insípido Neurogênico/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Adenoma/complicações , Adenoma/cirurgia , Adulto , China , Diabetes Insípido Nefrogênico/complicações , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/genética , Diabetes Insípido Neurogênico/diagnóstico , Feminino , Humanos , Mutação de Sentido Incorreto , Apoplexia Hipofisária/diagnóstico , Apoplexia Hipofisária/etiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Receptores de Vasopressinas/genética , Adulto Jovem
7.
NMR Biomed ; 33(5): e4256, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32045957

RESUMO

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non-invasive, non-radiation, and whole-body imaging techniques to investigate them. The aim of this study is to develop an ultra-small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro-vasculature in both animal (~10 µm in rat) and human brain. We hypothesized that the USPIO-SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10-fold compared with conventional MRI methods. Computer simulations were first performed with a double-cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO-SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO-SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3-fold and 19.9-fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO-SWI method exhibited its excellent ability to detect small vessels down to about 10 µm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10-fold increase in the USPIO-SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 µm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO-SWI method demonstrates higher potential in cerebrovascular disease investigations.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Meios de Contraste/química , Ferro/química , Imageamento por Ressonância Magnética , Animais , Arteríolas/diagnóstico por imagem , Arteríolas/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Simulação por Computador , Óxido Ferroso-Férrico/farmacologia , Humanos , Masculino , Imagens de Fantasmas , Ratos Wistar , Vênulas/diagnóstico por imagem , Vênulas/efeitos dos fármacos
8.
J Clin Lab Anal ; 34(5): e23191, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31901184

RESUMO

BACKGROUND: The differential diagnoses of patients hospitalized for respiratory infections due to influenza virus vs other pathogens are challenging. Our study investigated whether hematological parameters such as neutrophil (N), lymphocyte (L), platelet (PLT), and neutrophil-to-lymphocyte ratio (NLR) contributed in diagnosing influenza virus infections and in discriminating other respiratory infections. METHODS: We retrospectively analyzed the laboratory characteristics of 307 patients with respiratory infections caused by influenza/non-influenza virus and bacteria. The diagnostic abilities of hematological indexes were evaluated in the patients compared with 100 healthy people. RESULTS: The hematological parameters in patients with influenza virus infection were dramatically altered compared with those in the controls. Additionally, among the systemic inflammatory markers, the sensitivity of NLR for influenza detection was higher than that of N and L. PLT was significantly lower in influenza virus-positive infection than in influenza virus-negative infection. Moreover, when patients with influenza virus infection were cured, PLT returned to a normal level. The red blood cell (RBC) and hemoglobin (Hb) levels of influenza virus infection were higher than those of bacterial infection. Compared with traditional N and L, NLR and platelet-to-neutrophil (PNR) showed greater significance between influenza virus and bacterial infection (P < .01). CONCLUSION: Neutrophil-to-lymphocyte ratio with high sensitivity is a preferable diagnostic tool to screen influenza virus-infected patients than N and L. PLT accounts in the differential diagnoses of respiratory infections due to influenza virus and other pathogens among patients. In addition, RBC, Hb, NLR, and PNR can significantly differentiate between influenza virus infections and bacterial infections.


Assuntos
Contagem de Células Sanguíneas , Influenza Humana/sangue , Influenza Humana/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/sangue , Infecções Bacterianas/diagnóstico , Feminino , Hospitalização , Humanos , Influenza Humana/etiologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
9.
Neuroimage ; 200: 601-606, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158477

RESUMO

PURPOSE: To achieve sufficient precision of R1 (=1/T1) maps of the fetal brain in utero to perform QUEnch-assiSTed (QUEST) MRI in which a significant anti-oxidant-induced reduction in R1 indicates oxidative stress. METHODS: C57BL/6 mouse fetuses in utero were gently and non-surgically isolated and secured using a homemade 3D printed clip. Using a commercial receive-only surface coil, brain maps of R1, an index sensitive to excessive and continuous free radical production, were collected using either a conventional Cartesian or a non-Cartesian (periodically rotated overlapping parallel lines with enhanced reconstruction) progressive saturation sequence. Data were normalized to the shortest TR time to remove bias. To assess oxidative stress, brain R1 maps were acquired on the lipopolysaccharide (LPS) model of preterm birth ±â€¯rosiglitazone (ROSI, which has anti-oxidant properties); phosphate buffered saline (PBS) controls ±â€¯ROSI were similarly studied. RESULTS: Sufficient quality R1 maps were generated by a combination of the 3D printed clip, surface coil detection, non-Cartesian sequence, and normalization scheme ensuring minimal fetal movement, good detection sensitivity, reduced motion artifacts, and minimal baseline variations, respectively. In the LPS group, the combined caudate-putamen and thalamus region R1 was reduced (p < 0.05) with ROSI treatment consistent with brain oxidative stress; no evidence for oxidative stress was found in the pons region. In the PBS control group, brain R1's did not change with ROSI treatment. CONCLUSION: The sensitivity and reproducibility of the combined approaches described herein enabled first-time demonstration of regional oxidative stress measurements of the fetal brain in utero using QUEST MRI.


Assuntos
Encéfalo/diagnóstico por imagem , Embrião de Mamíferos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Estresse Oxidativo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Embrião de Mamíferos/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Diagnóstico Pré-Natal
10.
BMC Endocr Disord ; 19(1): 148, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883520

RESUMO

BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies. Patients with IAS usually complain of hypoglycemia without any previous insulin received. Glucocorticoids and immunosuppressants are used to treat IAS. CASE PRESENTATION: We report four patients with diabetes who were diagnosed with non-classical IAS and describe the treatment of these patients. Moreover, the differential diagnosis with hyperinsulinism is discussed. CONCLUSION: High levels of insulin autoantibodies, as well as hyperinsulinemic hypoglycemia, are found in patients with diabetes mellitus and prior exogenous insulin exposure. This situation that we classified as non-classical IAS should be attached importance to.


Assuntos
Doenças Autoimunes/induzido quimicamente , Insulina/administração & dosagem , Insulina/imunologia , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Injeções , Anticorpos Anti-Insulina/sangue , Masculino , Pessoa de Meia-Idade , Síndrome
11.
Mediators Inflamm ; 2019: 7659509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341422

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.


Assuntos
Ácidos e Sais Biliares/metabolismo , Disbiose/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Ensaios Clínicos como Assunto , Microbioma Gastrointestinal , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Camundongos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/terapia , Proteínas de Ligação a RNA/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Risco , Transdução de Sinais
12.
Nutr Cancer ; 70(7): 1075-1087, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30273070

RESUMO

Pancreatic cancer (PC) patients have poor prognosis and survival rate. Gemcitabine, the drug of choice has a dismal 15% response rate. Earlier, we reported that Garcinol alone and in combination with gemcitabine showed a dose-dependent favorable response on PC cell lines. This study probes the in vivo effects of dietary Garcinol on PC progression in transgenic PC mice (KPC; K-ras and p53 conditional mutant). KPC male mice were divided into: KC- Control diet; KGr-0.05% Garcinol diet; KGm-Gemcitabine injected; KGG - Garcinol diet + Gemcitabine injected groups. Changes in tumor progression, toxicity, or cell morphology were monitored by magnetic resonance imaging, Fore-stomach, and blood smear, respectively. Pancreatic Intraepithelial Neoplasia (mPanIN) grading with hematoxylin and eosin (H&E) staining was conducted on pancreas and validated by immunohistochemistry. The KGr group showed improved survival, no observable toxicity with marked reduction in papilloma formation in the fore-stomach, and a higher ratio of NK and NKT cells compared to Non-NK lymphocytes. Additionally, the KGr, KGm, and KGG groups showed reduction in tumor volumes and reduced number of advanced mouse PanIN3. Dietary Garcinol alone and in combination with gemcitabine retarded the progression of PC in transgenic PC mice, arresting the cancer in the earlier stages, improving prognosis and survival.


Assuntos
Neoplasias Pancreáticas/dietoterapia , Terpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Suplementos Nutricionais , Genes p53 , Genes ras , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos Transgênicos , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Subunidade beta da Proteína Ligante de Cálcio S100/imunologia , Proteína Smad4/imunologia , Taxa de Sobrevida , Terpenos/efeitos adversos , Gencitabina
13.
Bioorg Med Chem ; 26(19): 5274-5279, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-29653832

RESUMO

We report a screening procedure to predict ligand coordination to EuII and EuIII using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic GdIII is used as a surrogate for EuIII in the screening procedure to enable detection with magnetic resonance imaging. The screening procedure was tested using a set of eight ligands with known coordination to EuII and EuIII, and results were found to be consistent with expected binding. Validation of the screening procedure with known coordination chemistry enables use with new ligands in the future.


Assuntos
Európio/química , Ligantes , Imageamento por Ressonância Magnética , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Gadolínio/química , Oxirredução , Espectrometria por Raios X , Temperatura
14.
Chemistry ; 23(61): 15404-15414, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-28707809

RESUMO

EuII -containing complexes were studied with respect to properties relevant to their use as contrast agents for magnetic resonance imaging. The influences of molecular parameters and field strength on relaxivity were studied for a series of EuII -containing cryptates and their adducts with ß-cyclodextrins, poly-ß-cyclodextrins, and human serum albumin. Solid- and solution-phase characterization of EuII -containing complexes is presented that demonstrates the presence of inner-sphere molecules of water. Additionally, relaxivity, water-exchange rate, rotational correlation time, and electronic relaxation times were determined using variable-temperature 17 O NMR, nuclear magnetic relaxation dispersion, and electron paramagnetic resonance spectroscopic techniques. These results are expected to be instrumental in the design of future EuII -based contrast agents.

15.
Inflamm Res ; 66(12): 1075-1084, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28852776

RESUMO

OBJECTIVE: Malvidin is one of the most widespread anthocyanidins which exhibits significant antioxidant and anti-inflammatory activity. The aim of this paper is to investigate the effects of Malvidin on osteoarthritis (OA). MATERIALS AND METHODS: We created an animal model of OA using Wistar rats administered by monosodium iodoacetate (MIA). Effects of Malvidin on hyperalgesia were evaluated by paw pressure tests and compression threshold test. Articular chondrocytes were isolated from the OA rats to detect the apoptotic chondrocytes using senescence-associated ß-galactosidase (SA-ß-gal) staining kit. The expression levels of pro-inflammatory cytokines and matrix metalloproteinase (MMPs) were assessed by western blot and qPCR. Luciferase assay was used to determine the impact of Malvidin on nuclear factor-kappa B (NF-κB) pathway. RESULTS: Malvidin treatment exhibited significant pain-relieving effects in OA rats and decreased the expression level of apoptotic marker SA-ß-gal in chondrocytes. We found that the upregulated expressions of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and MMPs induced by MIA in cartilage tissues were significantly reversed by Malvidin. Furthermore, Malvidin inhibited NF-κB pathway via an NF-κB inhibitor (IκBα)-independent manner through suppressing p65 nuclear transportation in vitro. CONCLUSIONS: Our findings suggest that Malvidin significantly attenuates the OA-induced pain and inflammation by inhibiting NF-κB signaling pathway and suppressing pro-inflammatory cytokine expression and chondrocyte apoptosis.


Assuntos
Antocianinas/farmacologia , Anti-Inflamatórios/farmacologia , NF-kappa B/antagonistas & inibidores , Osteoartrite/metabolismo , Analgésicos , Animais , Antocianinas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Citocinas/genética , Citocinas/metabolismo , Células HEK293 , Humanos , Luciferases/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
16.
Inorg Chem ; 55(20): 9981-9988, 2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27244124

RESUMO

The 3+ and 2+ oxidation states of europium have drastically different magnetic and spectroscopic properties. Electrochemical measurements are often used to probe EuIII/II oxidation state changes, but a full suite of spectroscopic characterization is necessary to demonstrate conversion between these two oxidation states in solution. Here, we report the facile conversion of an europium(III) tetraglycinate complex into its EuII analogue. We present electrochemical, luminescence, electron paramagnetic resonance, UV-visible, and NMR spectroscopic data demonstrating complete reversibility from the reduction and oxidation of the 3+ and 2+ oxidation states, respectively. The EuII-containing analogue has kinetic stability within the range of clinically approved GdIII-containing complexes using an acid-catalyzed dissociation experiment. Additionally, we demonstrate that the 3+ and 2+ oxidation states provide redox-responsive behavior through chemical-exchange saturation transfer or proton relaxation, respectively. These results will be applicable to a wide range of redox-responsive contrast agents and Eu-containing complexes.

17.
Gynecol Obstet Invest ; 81(3): 193-201, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26336923

RESUMO

OBJECTIVE: To quantify gestation-dependent longitudinal changes in the magnetic resonance transverse relaxation time (T2) parameter of the major constituent regions of the mouse placenta and to evaluate their relative contributions to changes in overall placental T2. METHODS: Timed-pregnant CD-1 mice underwent magnetic resonance imaging at 7.0 T field strength, on gestational day 13 (GD13), GD15 and GD17. T2 of the placenta and its constituent high and low blood perfusion regions were quantified. A linear mixed-effects model was used to fit the T2 across gestation, and the significance of coefficients was tested. RESULTS: A decrease in the T2 values of the placenta and its constituent regions was observed across gestation. The temporal change in T2 was estimated to be -1.85 ms/GD (p < 0.0001) for the placenta, -1.00 ms/GD (p < 0.001) for the high-perfusion zones (HPZs) and -1.66 ms/GD (p < 0.0001) for the low-perfusion zones (LPZs). CONCLUSION: T2 of the constituent zones of the murine placenta decreases with advancing gestation. While the T2 of the LPZ is smaller than that of the HPZ, there is no difference in their decrease rate relative to that of the whole placenta (p = 0.24). The results suggest an increased role of constituent volume fractions in affecting overall gestation-dependent placental T2 decrease in mice.


Assuntos
Imageamento por Ressonância Magnética/veterinária , Placenta/diagnóstico por imagem , Placenta/fisiologia , Animais , Feminino , Idade Gestacional , Camundongos , Placenta/irrigação sanguínea , Gravidez
18.
Angew Chem Int Ed Engl ; 54(48): 14398-401, 2015 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-26428059

RESUMO

The Eu(II) ion rivals Gd(III) in its ability to enhance contrast in magnetic resonance imaging. However, all reported Eu(II)-based complexes have been studied in vitro largely because the tendency of Eu(II) to oxidize to Eu(III) has been viewed as a major obstacle to in vivo imaging. Herein, we present solid- and solution-phase characterization of a Eu(II)-containing cryptate and the first in vivo use of Eu(II) to provide contrast enhancement. The results indicate that between one and two water molecules are coordinated to the Eu(II) core upon dissolution. We also demonstrate that Eu(II)-based contrast enhancement can be observed for hours in a mouse.


Assuntos
Európio/química , Imageamento por Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/patologia , Animais , Cristalografia por Raios X , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Oxirredução
19.
Nucleic Acids Res ; 40(Web Server issue): W288-93, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22581768

RESUMO

In the context of the renewed interest of peptides as therapeutics, it is important to have an on-line resource for 3D structure prediction of peptides with well-defined structures in aqueous solution. We present an updated version of PEP-FOLD allowing the treatment of both linear and disulphide bonded cyclic peptides with 9-36 amino acids. The server makes possible to define disulphide bonds and any residue-residue proximity under the guidance of the biologists. Using a benchmark of 34 cyclic peptides with one, two and three disulphide bonds, the best PEP-FOLD models deviate by an average RMS of 2.75 Å from the full NMR structures. Using a benchmark of 37 linear peptides, PEP-FOLD locates lowest-energy conformations deviating by 3 Å RMS from the NMR rigid cores. The evolution of PEP-FOLD comes as a new on-line service to supersede the previous server. The server is available at: http://bioserv.rpbs.univ-paris-diderot.fr/PEP-FOLD.


Assuntos
Dissulfetos/química , Peptídeos Cíclicos/química , Peptídeos/química , Software , Internet , Conformação Proteica
20.
Gynecol Obstet Invest ; 78(1): 33-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24861575

RESUMO

OBJECTIVE: To evaluate gestational age-dependent changes in the T2 relaxation time in normal murine placentas in vivo. The role of susceptibility-weighted imaging (SWI) in visualization of the murine fetal anatomy was also elucidated. METHODS: Timed-pregnant CD-1 mice at gestational day (GD) 12 and GD17 underwent magnetic resonance imaging. Multi-echo spin echo and SWI data were acquired. The placental T2 values on GD12 and GD17 were quantified. To account for the influence of systemic maternal physiological factors on placental perfusion, maternal muscle was used as a reference for T2 normalization. A linear mixed-effects model was used to fit the normalized T2 values, and the significance of the coefficients was tested. Fetal SWI images were processed and reviewed for venous vasculature and skeletal structures. RESULTS: The average placental T2 value decreased significantly on GD17 (40.17 ± 4.10 ms) compared to the value on GD12 (55.78 ± 8.13 ms). The difference in normalized T2 values also remained significant (p = 0.001). Using SWI, major fetal venous structures like the cardinal vein, the subcardinal vein, and the portal vein were visualized on GD12. In addition, fetal skeletal structures could also be discerned on GD17. CONCLUSION: The T2 value of a normal murine placenta decreases with advancing gestation. SWI provided clear visualization of the fetal venous vasculature and bony structures. © 2014 S. Karger AG, Basel.


Assuntos
Feto/anatomia & histologia , Feto/irrigação sanguínea , Idade Gestacional , Imageamento por Ressonância Magnética , Animais , Feminino , Camundongos , Placenta/anatomia & histologia , Placenta/irrigação sanguínea , Gravidez , Veias/embriologia
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