Rheumatic diseases are a group of chronic autoimmune disorders that involve multiple organs or systems and have high mortality. The mechanisms of these diseases are still ill-defined, and targeted therapeutic strategies are still challenging for physicians. Recent research indicates that cell metabolism plays important roles in the pathogenesis of rheumatic diseases. In this review, we mainly focus on lipid metabolism profiles (dyslipidaemia, fatty acid metabolism) and mechanisms in rheumatic diseases and discuss potential clinical applications based on lipid metabolism profiles.

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This study was designed to explore the effects of exosomal miR‐421 secreted by cancer‐associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF‐derived exos (CAF‐exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR‐421, sirtuin‐3 (SIRT3), and hypoxia duciblefactors‐1 alpha (HIF‐1α) levels. Cell counting kit‐8 (CCK‐8), wound‐healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual‐luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR‐421 and SIRT3. Chromatin immunoprecipitation (f)‐verified H3K9Ac enrichment in the HIF‐1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR‐421 from CAFs on PC. CAFs and exos were successfully isolated. CAF‐exo‐treated PC cells highly expressed miR‐421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR‐421 increased the expression of SIRT3. SIRT3 is a target of miR‐421, and inhibiting the expression of SIRT3 reversed the negative effects of miR‐421 knockdown on PC cell. Knocking down miR‐421 in CAF‐exo inhibited the expression of HIF‐1α in PC cells. Moreover, SIRT3‐mediated HIF‐1α expression by regulating H3K9Ac. HIF‐1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR‐421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR‐421 attenuated CAF‐exo induced tumor growth. Exosomal miR‐421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF‐1α axis. This study provided insights into the molecular mechanism of PC.

Background: Clinically, IgA nephropathy has a variety of symptoms including paroxysmal gross hematuria, nephritic and nephrotic syndrome. This study aimed at investigating hub geneand genes modular related to IgA nephropathy clinical characteristics by using weighted gene co-expression network analysis combining clinical, microarray and network database parameters. Methods: We collected 32 human samples from the European Renal cDNA Bank and used RMA method to preprocess the data and utilize the limma package to obtain differentially expressed gene in renal interstitium and glomeruli. We used the WGCNA package to construct the gene co-expression of differential expression genes and identify hub genes associated with clinical characteristics in renal interstitium and glomeruli, respectively. Gene ontology enrichment analysis and KEGG analysis for hub genes which associated with clinical characteristics were performed by DAVID. PPI information was acquired from STRING. Results: For glomeruli, 1470 genes differentially expressed between IgA nephropathy patients and healthy control, containing 10 hub genes associated with age, 8 hub genes associated with sex, 48 hub genes associated with Bp enrichd in ERK1 and ERK2 cascade and Rap1 signaling pathway, 223 hub genes associated with BMI enrich in organic acid catabolic process and fatty acid degradation pathway, 136 hub genes associated GFR enriched in immune response and PI3K-Akt signaling pathway, 82 hub genes associated with proteinuria enriched in extracellular matrix organization and PI3K-Akt signaling pathway. In tubulointerstitium, there were 480 genes differentially expressed between IgA nephropathy patients and healthy control. Among 480 DEGs, 6 hub genes associated with age, 15 hub genes associated with sex, 35 hub genes associated with Bp enrichd in positive regulation of apoptotic process, 87 hub genes associated with GFR enriched in negative regulation of macromolecule metabolic process and RNA transport, 33 hub genes associated with proteinuria enriched in regulation of apoptotic process and FoxO signaling pathway. PPI enrichment analysis shown that all hub genes sets are biologically connected cluster. Conclusions: We made a preliminary investigation on molecular mechanisms of relationship between IgA nephropathy and clinical characteristics and identified hub genes and pathways closely related with BMI, GFR and Proteinuria in IgA nephropathy by a series of bioinformatics analysis.