RESUMO
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-ß signalling, VD has been proposed as an antifibrotic treatment. DESIGN: We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD. RESULTS: Treating phHSC with VD ameliorated TGF-ß-induced fibrogenesis via both VDR-dependent and VDR-independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of pro-fibrogenic genes was higher in patients carrying the G allele. CONCLUSIONS: VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.
Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Calcitriol/fisiologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Vitamina D/farmacologia , Adulto , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes/métodos , Células Estreladas do Fígado/fisiologia , Humanos , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/fisiologia , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/fisiologia , Vitamina D/sangue , Adulto JovemRESUMO
Samples of the secondary uranium minerals collected in the abandoned uranium mine at Pecs (Hungary) were investigated by two micro-techniques: scanning electron microscopy (SEM/EDX) and micro-Raman spectroscopy (MRS). They were applied to locate U-rich particles and identify the chemical form and oxidation state of the uranium compounds. The most abundant mineral was a K and/or Na uranyl sulphate (zippeite group). U(VI) was also present in the form showing intensive Raman scattering at 860 cm(-1) which can be attributed to uranium trioxide. This research has shown the successful application of micro-Raman spectroscopy for the identification of uranyl mineral species on the level of individual particles.