ABSTRACT
AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A ¹H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R²Y of 0.784 and a Q²Y of 0.598. Twelve metabolites, such as pyruvate, phenylalanine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: ¹H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future.
Subject(s)
Liver Cirrhosis/metabolism , Liver Cirrhosis/physiopathology , Metabolome , Nuclear Magnetic Resonance, Biomolecular/methods , Adult , Aged , Female , Humans , Liver Cirrhosis/pathology , Male , Middle Aged , Models, Statistical , Pilot Projects , Principal Component Analysis , Reproducibility of ResultsABSTRACT
OBJECTIVE: To investigate the aberrance of histone H3 lysine 4 trimethylation (H3K4me3) in patients with IgA nephropathy (IgAN). METHODS: In 15 patients with IgAN and 15 healthy volunteers, H3K4me3 variations in peripheral blood mononuclear cells (PBMCs) were analyzed using chromatin immunoprecipitation and microarray analysis (ChIP-chip). ChIP real-time PCR was used to validate the microarray results. Quantitative real-time PCR (qRT-PCR) was carried out to examine the correlations between the mRNA expression profiles and H3K4me3 levels. RESULTS: We identified 83 genes that displayed significant H3K4me3 differences in IgAN patients compared with healthy subjects. Among them, 39 genes showed increased H3K4me3 and 44 genes had decreased H3K4me3 levels. The results of ChIP real-time PCR were well consistent with the microarray data. Quantitative RT-PCR revealed the correlations between the mRNA expressions and the methylation levels of H3K4me3. CONCLUSION: IgAN patients have significant alterations in H3K4me3, and the genes with aberrant H3K4me3 may provide insights into the pathogenesis of IgAN.
Subject(s)
CpG Islands/genetics , DNA Methylation , Glomerulonephritis, IGA/genetics , Histones/genetics , Case-Control Studies , Female , Glomerulonephritis, IGA/metabolism , Histones/metabolism , Humans , Leukocytes, Mononuclear/metabolism , Lysine/genetics , Lysine/metabolism , MaleABSTRACT
OBJECTIVE: To evaluate the correlation between multiple resistance of Neisseria gonorrhoeae and mutations in the inverted sequence within the mtrR promoter region. METHODS: The susceptibilities of 56 Neisseria gonorrhoeae to 5 antibiotic agents were tested by disc diffusion method. 13 bp inverted sequences positioned within the mtrR promoter region were amplified by PCR and examined by single strand conformation polymorphism technology. According to the results of SSCP, 12 strains were selected and were directly sequenced, and their nucleotide sequences were compared with those of susceptible strain ATCC19 424. RESULTS: In the 56 strains of Neisseria gonorrhea, 5 strains were susceptible to all antibiotics and 22 strains were resistant to one antibiotic agent. In the 19 strains that were resistant to 2 antibiotic agents, 2 had mutations in a 13 bp inverted sequence positioned within the mtrR promoter region. Another 7, 2 and 1 strain which was resistant to 3,4 and 5 antibiotic agents respectively all had mutations in a 13 bp inverted sequence positioned within the mtrR promoter region. All of the 12 strains which contained the same mutation exhibited a single base pair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region. CONCLUSION: Deletions in the 13 bp inverted sequence positioned within the mtrR promoter region mediate multiple resistances in Neisseria gonorrhoeae. A single base pair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region is associated with multiple resistance.
