Anti-FN1 monoclonal antibody, clone CD-2

Increased cytokine and inflammatory-related transcripts are found in the ventral midbrain, a dopamine neuron-rich region associated with schizophrenia symptoms. In fact, half of schizophrenia cases can be defined as having a "high inflammatory/immune biotype." Recent studies implicate both complement and macrophages in cortical neuroinflammation in schizophrenia. Our aim was to determine whether measures of transcripts related to phagocytosis/macrophages (CD163, CD64, and FN1), or related to macrophage adhesion [intercellular adhesion molecule 1 (ICAM1)], or whether CD163+ cell density, as well as protein and/or gene expression of complement pathway activators (C1qA) and mediators (C3 or C4), are increased in the midbrain in schizophrenia, especially in those with a high inflammatory biotype. We investigated whether complement mRNA levels correlate with macrophage and/or microglia and/or astrocyte markers. We found CD163+ cells around blood vessels and in the parenchyma and increases in ICAM1, CD163, CD64, and FN1 mRNAs as well as increases in all complement transcripts in the midbrain of schizophrenia cases with high inflammation. While we found positive correlations between complement transcripts (C1qA and C3) and microglia or astrocyte markers across diagnostic and inflammatory subgroups, the only unique strong positive correlation was between CD163 and C1qA mRNAs in schizophrenia cases with high inflammation. Our study is the first to suggest that more circulating macrophages may be attracted to the midbrain in schizophrenia, and that increased macrophages are linked to increased complement pathway activation in tissue and may contribute to dopamine dysregulation in schizophrenia. Single-cell transcriptomic studies and mechanistic preclinical studies are required to test these possibilities.

Papillary thyroid carcinoma (PTC) has been increasing across the world with incomplete understanding of its pathogenesis. We aimed to investigate gene alterations and biomarkers contributing to PTC development. A total of five eligible microarray datasets including 94 PTC and 81 normal thyroid samples were included to identify gene expression signatures. Using integrative meta-analysis of expression data (INMEX) program, we identified a total of 2699 differentially expressed genes (DEGs) (1333 overexpressed and 1366 underexpressed genes) in PTC relative to normal thyroid samples. The top 100 upregualted and downregulated DEGs identified in the meta analysis were further validated in The Cancer Genome Atlas (TCGA) dataset for PTC with high consistency. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed pathways in cancer, proteoglycans in cancer, focal adhesion, axon guidance, and ECM-receptor interaction among the top 5 most enriched pathways. Network-based meta-analysis identified FN1 and TRAF6 to be the most highly ranked hub genes among the overexpressed and underexpressed genes, respectively, both of which are involved in pathways in cancer. The most enriched terms for Gene Ontology (GO) of biological processes, cellular component, and molecular function were signal transduction, cytoplasm, and protein binding, respectively. Our meta-analysis comprehensively investigated DEGs, hub genes, enriched pathways and GO terms for PTC, which might provide additional approaches to explore the molecular mechanisms underlying the pathophysiology of PTC, and identify biomarkers and therapeutic targets toward PTC.