RESUMO
Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.
Assuntos
Diospyros/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Estado Pré-Diabético/tratamento farmacológico , Biomarcadores/metabolismo , Western Blotting , Proteínas do Citoesqueleto/metabolismo , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Placebos , Extratos Vegetais/farmacologia , Estado Pré-Diabético/metabolismo , Análise de Componente Principal , Proteoma/metabolismo , Saliva/metabolismo , Espectrometria de Massas em TandemRESUMO
Corticotropin releasing factor (CRF) and its cognate receptors, defined as Type 1 and Type 2 have been localized within the cerebellum. The Type 2 CRF receptor (CRF-R2) is known to have both a full length (CRF-R2alpha) and a truncated (CRF-R2alpha-tr) isoform. A recent study documented CRF-R2alpha primarily in Bergann glia and astrocytes, as well as in populations of Purkinje cells in the adult cerebellum. The goal of the present study is to determine if CRF-R2alpha is present in the postnatal cerebellum, and if so to describe its cellular distribution. RT-PCR data showed that CRF-R2alpha is expressed in the mouse cerebellum from birth through postnatal day 21. Between birth and P14, CRF-R2alpha-immunoreactivity was localized within the somata of Purkinje cells, and migrating GABAergic interneurons. GFAP-immunoreactive astrocytes, including Bergmann glia, also expressed CRF-R2alpha-immunoreactivity from P3-P14. There is a change, however, in CRF-R2alpha immunolabeling within neurons as the cerebellum matures. Compared to its expression in the adult cerebellum, Purkinje cells, and GABAergic interneurons showed more extensive CRF-R2alpha immunolabeling during early postnatal development. We postulate that CRF-R2alpha could be involved in developmental events related to the survival and differentiation of Purkinje cells and GABAergic neurons, whereas in the adult, this isoform of the CRF receptor family is likely involved in modulating Bergmann glia that have been shown to play a role in regulating the synaptic environment around Purkinje neurons.
Assuntos
Córtex Cerebelar/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Animais , Córtex Cerebelar/crescimento & desenvolvimento , Hormônio Liberador da Corticotropina/metabolismo , Imunofluorescência , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Interneurônios/fisiologia , Isomerismo , Camundongos , Camundongos Endogâmicos C57BL , Neuroglia/metabolismo , Células de Purkinje/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ácido gama-Aminobutírico/fisiologiaRESUMO
PURPOSE: To prospectively evaluate the diagnostic performance of double-echo gradient-echo (GRE) chemical shift magnetic resonance (MR) imaging in the differentiation of angiomyolipoma (AML) with minimal fat from other renal neoplasms, with pathologic examination or follow-up data serving as the reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Double-echo GRE chemical shift MR imaging was performed in 55 patients (29 men and 26 women; mean age, 49 years +/- 14 [standard deviation]) with 55 renal tumors, including 37 (67%) pathologically proved tumors (23 renal cell carcinomas, nine AMLs, two oncocytomas, two lymphomas, and one reninoma) and 18 (33%) clinically diagnosed tumors (17 AMLs and one indeterminate malignancy). All tumors showed no intratumoral fat and had homogeneous enhancement and a prolonged or gradual enhancement pattern on biphasic helical computed tomographic scans. Signal intensity was measured in the renal tumor and spleen on in-phase and opposed-phase images. The signal intensity index and tumor-to-spleen ratio in AMLs and non-AMLs were calculated and compared with the Student t test. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the signal intensity index and tumor-to-spleen ratio and to extract the optimal cut-off values in the differentiation of AMLs and non-AMLs. RESULTS: The signal intensity index and tumor-to-spleen ratio were different between AMLs (42% +/- 11 and -43% +/- 17, respectively) and non-AMLs (5% +/- 14 and -4% +/- 16, respectively) (P < .001). The area under the ROC curve was 0.975 for the signal intensity index and 0.952 for the tumor-to-spleen ratio. For differentiation of AMLs from non-AMLs, sensitivity and specificity were (a) 96% and 93%, respectively, with a signal intensity index of 25% and (b) 88% and 97%, respectively, with a tumor-to-spleen ratio of -32%. CONCLUSION: Double-echo GRE chemical shift MR imaging can be used to differentiate AML with minimal fat from other renal neoplasms.
Assuntos
Angiomiolipoma/patologia , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Corticotropin releasing factor (CRF) is known to be involved in the stress response and in some degenerative brain disorders. In addition, CRF has a role as a neuromodulator in adult cerebellar circuits. Data from developmental studies suggest a putative role for CRF as a trophic factor during cerebellar development. In this study, we investigated the trophic role for CRF family of peptides by culturing cerebellar neurons in the presence of CRF, urocortin or urocortin II. Primary cell cultures of cerebella from embryonic day 18 mice were established, and cells were treated for either 1, 5 or 9 days with Basal Medium Eagles complete medium alone or complete medium with 1 microM CRF, urocortin, or urocortin II. The number of GABA-positive neurons in each treatment condition was counted at each culture age for monitoring the changes in neuronal survival. Treatment with 1 microM CRF or 1 microM urocortin increased the survival of GABAergic neurons at 6 days in vitro and 10 days in vitro, and this survival promoting effect was abolished by treatment with astressin in the presence of those peptides. Based on these data, we suggest that CRF or urocortin has a trophic role promoting the survival of cerebellar GABAergic neurons in cultures.