Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis.

Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc. Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration. Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-ß receptor inhibitor (SB-525334), and so on. Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.

Transcriptome-based analyses reveal venom diversity in two araneomorph spiders, Psechrus triangulus and Hippasa lycosina.

The spiders Psechrus triangulus and Hippasa lycosina are widely distributed in Yunnan Province, China, and are important natural enemies of agricultural pests, yet studies regarding the composition of their venom are lacking. In this study, cDNA libraries were constructed from venom gland tissue of P. triangulus and H. lycosina and used for transcriptomic analysis. From the analysis, 39 and 31 toxin-like sequences were predicted for P. triangulus and H. lycosina, respectively. The predicted neurotoxin sequences were categorized according to cysteine sequence motifs, and the predicted neurotoxin sequences of P. triangulus and H. lycosina could be classified into 9 and 6 toxin families, respectively. In addition, potential acetylcholinesterase, hyaluronidase, and astaxanthin-like metalloproteinases were identified through annotation. In summary, transcriptomic techniques were invaluable in mining the gene expression information from these two spider species to explore the toxin composition of their venom and determine how they differ. Studies of this type provide essential baseline data for studying the evolution and physiological activities of spider toxins and for the potential development of medicinal compounds.

[Relationship of serum levels of HGF and MMP-9 with disease activity of patients with systemic lupus erythematosus].

OBJECTIVE: To determine the relationship of serum hepatocyte growth factor (HGF) and matrix metalloproteinase-9 (MMP-9) levels with the disease activity of systemic lupus erythematosus (SLE). METHODS: Serum levels of HGF and MMP-9 were measured by ELISA in 36 patients with SLE and 30 healthy subjects as controls. RESULT: (1)Significantly increased serum level of HGF was found in SLE patients as compared with that in healthy controls (P<0.001), but serum level of MMP-9 in SLE patients decreased (P<0.001). Serum level of HGF was significantly decreased after treatment in SLE patients (P<0.05), but serum level of MMP-9 was increased (P<0.05). (2)Serum level of HGF was markedly higher in patients with active disease (24 cases) than those with inactive disease (P<0.05), but serum level of MMP-9 was lower (P<0.05). (3)Significantly increased serum level of HGF was found in patients with renal damage (16 cases) than those without (P<0.001), but serum level of MMP-9 was lower in patients with renal damage than those without (P<0.005). (4)Serum level of HGF was higher in patients with arthritis (23 cases) than those without (P<0.01), but serum level of MMP-9 had no significant difference in two groups (P>0.05). (5)The area of ROC curve was 0.707 and the sensitivity was 66.7% if serum level of HGF was served as diagnostic standard. The area of ROC curve was 0.984 and the sensitivity was 97.2% if serum level of MMP-9 was served as diagnostic standard. The sensitivity was 66.7% (24/36) if the two markers were examined simultaneously. CONCLUSION: The data suggest that HGF and MMP-9 could be involved in the pathogenesis of SLE, and serum levels of HGF and MMP-9 be used as markers to monitor disease activity, renal damage, disease progression and amelioration in SLE.