Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.

• MeSH
• COVID-19 * MeSH
• Humans MeSH
• Matrix Metalloproteinase 9 genetics   metabolism   MeSH
• Intercellular Signaling Peptides and Proteins MeSH
• Mitochondria metabolism   MeSH
• Signal Transduction MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Expression features of genetic landscape which predispose an individual to the type 1 diabetes are poorly understood. We addressed this question by comparing gene expression profile of freshly isolated peripheral blood mononuclear cells isolated from either patients with type 1 diabetes (T1D), or their first-degree relatives or healthy controls. Our aim was to establish whether a distinct type of 'prodiabetogenic' gene expression pattern in the group of relatives of patients with T1D could be identified. Whole-genome expression profile of nine patients with T1D, their ten first-degree relatives and ten healthy controls was analysed using the human high-density expression microarray chip. Functional aspects of candidate genes were assessed using the MetaCore software. The highest number of differentially expressed genes (547) was found between the autoantibody-negative healthy relatives and the healthy controls. Some of them represent genes critically involved in the regulation of innate immune responses such as TLR signalling and CCR3 signalling in eosinophiles, humoral immune reactions such as BCR pathway, costimulation and cytokine responses mediated by CD137, CD40 and CD28 signalling and IL-1 proinflammatory pathway. Our data demonstrate that expression profile of healthy relatives of patients with T1D is clearly distinct from the pattern found in the healthy controls. That especially concerns differential activation status of genes and signalling pathways involved in proinflammatory processes and those of innate immunity and humoral reactivity. Thus, we posit that the study of the healthy relative's gene expression pattern is instrumental for the identification of novel markers associated with the development of diabetes.

• MeSH
• Molecular Sequence Annotation MeSH
• Autoimmunity MeSH
• Autoantibodies biosynthesis   genetics   MeSH
• Antigens, CD genetics   immunology   MeSH
• Genome-Wide Association Study MeSH
• Diabetes Mellitus, Type 1 genetics   immunology   pathology   MeSH
• Child MeSH
• Adult MeSH
• Immunity, Humoral MeSH
• Interleukin-1 genetics   immunology   MeSH
• Infant MeSH
• Leukocytes, Mononuclear immunology   metabolism   pathology   MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Primary Cell Culture MeSH
• Immunity, Innate MeSH
• Receptors, CCR3 genetics   immunology   MeSH
• Gene Expression Regulation immunology   MeSH
• Family MeSH
• Signal Transduction MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Toll-Like Receptors genetics   immunology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH