We have screened candidate marker genes for the diagnosis of osteoarthritis and predicted their regulatory mechanisms. Six expression chips of tissue samples and one expression chip of peripheral blood mononuclear cell (PMBC) samples were obtained from the GEO database. Differential analysis, GSEA, and WGCNA were performed on the integra-ted tissue sample data with batch correction. Can-didate genes were obtained from the intersection of the genes significantly related to osteoarthritis in the WGCNA and the differentially expressed genes. ROC analysis was performed on the candidate genes in the tissue and PMBC samples. Genes with AUC values greater than 0.6 were retained as final candidates, and their upstream regulatory miRNAs were predicted. A total of 106 genes with differential expression were found in osteoarthritis tissue samples, which were mainly enriched in cell cycle and p53 signalling pathways. WGCNA selected a gene module significantly correlated with the occurrence of osteoarthritis. Fourteen candidate genes were obtained from the intersection of the genes in the module and the differentially expressed genes. ROC analysis showed that among these 14 candidate genes, only ADM, CX3CR1 and GADD45A had AUC values greater than 0.6 in both tissue and PMBC samples. The AUC values of the gene set of these three genes were greater than 0.7. Multiple miRNAs were predicted to be regulators of these three genes. ADM, CX3CR1 and GADD45A have potential as diagnostic marker genes for osteoarthritis and may be regulated by multiple miRNAs.

• MeSH
• buněčné dělení MeSH
• buněčný cyklus MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• osteoartróza * diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Commonly studied in the context of legume-rhizobia symbiosis, biological nitrogen fixation (BNF) is a key component of the nitrogen cycle in nature. Despite its potential in plant breeding and many years of research, information is still lacking as to the regulation of hundreds of genes connected with plant-bacteria interaction, nodulation, and nitrogen fixation. Here, we compared root nodule transcriptomes of red clover (Trifolium pratense L.) genotypes with contrasting nitrogen fixation efficiency, and we found 491 differentially expressed genes (DEGs) between plants with high and low BNF efficiency. The annotation of genes expressed in nodules revealed more than 800 genes not yet experimentally confirmed. Among genes mediating nodule development, four nod-ule-specific cysteine-rich (NCR) peptides were confirmed in the nodule transcriptome. Gene duplication analyses revealed that genes originating from tandem and dispersed duplication are significantly over-represented among DEGs. Weighted correlation network analysis (WGCNA) organized expression profiles of the transcripts into 16 modules linked to the analyzed traits, such as nitrogen fixation efficiency or sample-specific modules. Overall, the results obtained broaden our knowledge about transcriptomic landscapes of red clover's root nodules and shift the phenotypic description of BNF efficiency on the level of gene expression in situ.

• Publikační typ
• časopisecké články MeSH

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption or a secondary cause of hepatic steatosis. The prevalence of NAFLD is increasing worldwide and its management has become a public health concern. Animal models are traditionally used to elucidate disease mechanisms and identify potential drug targets; however, their translational aspects in human diseases have not been fully established. This study aimed to clarify the utility of animal models for translational research by assessing their relevance to human diseases using gene expression analysis. Weighted gene co-expression network analysis of liver tissues from Western diet (WD)-induced NAFLD mice was performed to identify the modules associated with disease progression. Moreover, the similarity of the gene co-expression network across species was evaluated using module preservation analysis. Nineteen disease-associated modules were identified. The brown module was positively associated with disease severity, and functional analyses indicated that it may be involved in inflammatory responses in immune cells. Moreover, the gene co-expression network of the brown module was highly preserved in human NAFLD liver gene expression datasets. These results indicate that WD-induced NAFLD mice have similar gene co-expression networks (especially genes associated with inflammatory responses) to humans and are thought to be a useful experimental tool for preclinical research on NAFLD. Keywords: Nonalcoholic fatty liver disease (NAFLD), Weighted gene co-expression network analysis (WGCNA), Western diet (WD).

• MeSH
• játra metabolismus   patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• nealkoholová steatóza jater * genetika   metabolismus   etiologie   patologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• transkriptom * MeSH
• západní dieta * škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.

• MeSH
• bariatrická chirurgie MeSH
• dospělí MeSH
• genové regulační sítě MeSH
• lidé středního věku MeSH
• lidé MeSH
• morbidní obezita metabolismus   patologie   chirurgie   MeSH
• nitrobřišní tuk cytologie   metabolismus   patologie   MeSH
• omentum cytologie   metabolismus   patologie   chirurgie   MeSH
• podkožní břišní tuk cytologie   metabolismus   patologie   MeSH
• proteomika MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Brown adipose tissue (BAT) has been suggested to play an important role in lipid and glucose metabolism in rodents and possibly also in humans. In the current study, we used genetic and correlation analyses in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), to identify genetic determinants of BAT function. Linkage analyses revealed a quantitative trait locus (QTL) associated with interscapular BAT mass on chromosome 4 and two closely linked QTLs associated with glucose oxidation and glucose incorporation into BAT lipids on chromosome 2. Using weighted gene coexpression network analysis (WGCNA) we identified 1,147 gene coexpression modules in the BAT from BXH/HXB rats and mapped their module eigengene QTLs. Through an unsupervised analysis, we identified modules related to BAT relative mass and function. The Coral4.1 coexpression module is associated with BAT relative mass (includes Cd36 highly connected gene), and the Darkseagreen coexpression module is associated with glucose incorporation into BAT lipids (includes Hiat1, Fmo5, and Sort1 highly connected transcripts). Because multiple statistical criteria were used to identify candidate modules, significance thresholds for individual tests were not adjusted for multiple comparisons across modules. In summary, a systems genetic analysis using genomic and quantitative transcriptomic and physiological information has produced confirmation of several known genetic factors and significant insight into novel genetic components functioning in BAT and possibly contributing to traits characteristic of the metabolic syndrome.

• MeSH
• genetická predispozice k nemoci genetika   MeSH
• glukosa metabolismus   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• krysa rodu rattus MeSH
• lokus kvantitativního znaku genetika   MeSH
• metabolický syndrom genetika   metabolismus   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVES: This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode. METHODS: In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms. CONCLUSION: This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools. LIMITATIONS: The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.

• Publikační typ
• časopisecké články MeSH