• Cellular proliferation
• JAK-STAT
• Lipid metabolism
• MAPK
• OASL
• Psoriasis

• Humans
• Animals
• Mice
• Psoriasis/drug therapy
• Psoriasis/metabolism
• Psoriasis/pathology
• Inflammation/metabolism
• Inflammation/drug therapy
• Inflammation/pathology
• Flavonols/pharmacology
• Male
• Keratinocytes/metabolism
• Keratinocytes/drug effects
• Imiquimod
• Cell Proliferation/drug effects
• Female
• STAT1 Transcription Factor/metabolism
• MAP Kinase Signaling System/drug effects
• Lipid Metabolism/drug effects
• Janus Kinase 1/metabolism
• HaCaT Cells

• Alternative method
• Co-culture system
• Crosstalk
• Gene expression
• Reconstructed human epidermis (RhE) model
• Skin sensitization

• Humans
• Coculture Techniques
• Dinitrochlorobenzene/toxicity
• THP-1 Cells
• Keratinocytes/metabolism
• Keratinocytes/drug effects
• Epidermis/metabolism
• Epidermis/drug effects
• Culture Media
• Monocytes/metabolism
• Monocytes/drug effects
• Gene Expression/drug effects
• Gene Expression Regulation/drug effects

• Psoriasis
• immunology
• inflammation
• metabolism
• proteomics

• IRF1
• Inflammation
• Proliferation
• Psoriasis
• RSAD2

• Psoriasis/metabolism
• Psoriasis/pathology
• Animals
• MAP Kinase Kinase Kinases/metabolism
• MAP Kinase Kinase Kinases/genetics
• Keratinocytes/metabolism
• Keratinocytes/pathology
• Keratinocytes/drug effects
• Mice
• NF-kappa B/metabolism
• Humans
• Down-Regulation/physiology
• Cell Proliferation/physiology
• Male
• Signal Transduction/physiology
• Mice, Inbred C57BL
• Imiquimod/toxicity
• Skin/metabolism
• Skin/pathology

• Biomarker
• Breast cancer
• OAS genes
• Prognosis
• Treatment

• Humans
• Breast Neoplasms/genetics
• Breast Neoplasms/diagnosis
• 2',5'-Oligoadenylate Synthetase/genetics
• Female
• Cell Line, Tumor
• DNA Methylation
• Gene Expression Regulation, Neoplastic
• Promoter Regions, Genetic
• Biomarkers, Tumor/genetics
• Computer Simulation
• Cell Proliferation
• Computational Biology/methods
• Clinical Relevance

• bioinformatics
• gene signature
• hub genes
• immune grouping
• immune infiltration
• immune-targeted therapy

• research was supported by the Transversal Research Project of Kuntuo Xincheng Pharmaceutical Research & Development

• HIF-1α signalling pathway
• ISG15
• cell multiplication
• psoriasis

• Animals
• Mice
• Antiviral Agents
• Cell Proliferation
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Interferons/metabolism
• Keratinocytes/metabolism
• Psoriasis/metabolism
• Vascular Endothelial Growth Factor C/metabolism

• SIRT1
• dermatology
• oxidative stress
• psoriasis
• sirtuins

• trpm8
• corneal wound healing
• interferon
• squamous metaplasia

• Mice
• Animals
• Mice, Inbred C57BL
• Corneal Injuries/metabolism
• Cornea/metabolism
• Epithelium, Corneal/metabolism
• Wound Healing/physiology
• Corneal Opacity/metabolism
• TRPM Cation Channels/genetics
• TRPM Cation Channels/metabolism

• bioinformatics
• biomarkers
• diabetes complications
• ulcer

• Bladder cancer
• Expression signature
• Immune cell infiltration
• OAS gene family
• Prognosis

• 2',5'-Oligoadenylate Synthetase/genetics
• Adenine Nucleotides
• Humans
• Ligases
• Oligoribonucleotides
• Prognosis
• Tumor Microenvironment/genetics
• Urinary Bladder Neoplasms/genetics

• 202103021223238 Basic Research Program of Shanxi Province
• 22007063 National Natural Science foundation of China
• 82170523 National Natural Science foundation of China
• 2020XM01 Key Medical Science and Technology Program of Shanxi Province
• 1331KFC Shanxi "1331" Project Quality and Efficiency Improvement Plan
• Shanxi “1331” Project Quality and Efficiency Improvement Plan

Psoriasis is a common inflammatory skin disease that has a great impact on patients’ physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown.

The expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated via the sva software package, and differentially expressed genes (DEGs) between psoriasis and healthy skin were screened by the limma package. Furthermore, GO and KEGG pathway enrichments for the DEGs were performed using the Clusterprofiler package. Protein–protein interaction (PPI) networks for the DEGs were then constructed to identify hub genes. scGESA analysis was performed on a single-cell RNA sequencing dataset via irGSEA. In order to find the cytokines correlated with the hub genes expression, single cell weighted gene co-expression network analyses (scWGCNA) were utilized to build a gene co-expression network. Furthermore, the featured genes of psoriasis found in suprabasal keratinocytes were intersected with hub genes. We then analyzed the expression of the intersection genes and cytokines in the integrated dataset. After that, we used other datasets to reveal the changes in the intersection genes’ expression levels during biological therapy. The relationship between intersection genes and PASI scores was also explored.

We identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines—IL36G, MIF, and IL17RA—were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate.

IL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.

• Antiviral Agents
• Computational Biology
• Cytokines/genetics
• Gene Expression Profiling
• Humans
• Interleukin-1/genetics
• Interleukins/genetics
• Methotrexate
• Psoriasis/genetics

• National Natural Science Foundation of China

• Adenosine monophosphate-activated protein kinase
• Inflammation
• Nicotinamide phosphoribosyltransferase
• Psoriasis
• Silent information regulator 1

Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis.

To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis.

The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The “WGCNA” R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01).

A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences.

The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis. This may also provide new research ideas for the prevention and treatment of psoriasis in the future.

• Psoriasis
• MicroRNAs
• Weighted gene co-expression network analysis
• Functional enrichment
• MicroRNA-mRNA regulatory network

Psoriasis is a condition in which skin cells build up and form itchy scales and dry patches. It is also considered a common lifelong disease with an unclear pathogenesis. Furthermore, an effective cure for psoriasis is still unavailable. Reductive apoptosis of keratinocytes and immune infiltration are common in psoriasis. This study aimed to explore underlying functions of key apoptosis-related genes and the characteristics of immune infiltration in psoriasis. We used GSE13355 and GSE30999 to screen differentially expressed apoptosis related genes (DEARGs) in our study. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene set enrichment analysis (GSEA) were performed using clusterProfiler package. Protein–protein interaction (PPI) network was constructed to acquire key DEARGs. Transcription factor (TF)–target and miRNA–mRNA network analyses, drug sensitivity prediction, and immune infiltration were applied. Key DEARGs were validated using real-time quantitative PCR (RT-qPCR).

We identified 482 and 32 DEARGs from GSE13355 and GSE30999, respectively. GO analysis showed that DEARGs were commonly enriched in cell chemotaxis, receptor ligand activity, and signaling receptor activator activity. KEGG pathway analysis indicated that viral protein interaction with cytokine and cytokine receptor was maximally enriched pathway. The GSEA analysis of GSE13355 and GSE30999 demonstrated a high consistency degree of enriched pathways. Thirteen key DEARGs with upregulation were obtained in the PPI network. Eleven key DEARGs were confirmed using RT-qPCR. Additionally, 5 TFs and 553 miRNAs were acquired, and three novel drugs were predicted. Moreover, Dendritic.cells.activated exhibited high levels of immune infiltration while Mast.cells.resting showed low levels of immune infiltration in psoriasis groups.

Results of this study may reveal some insights into the underlying molecular mechanism of psoriasis and provide novel targeted drugs.

The online version contains supplementary material available at 10.1186/s41065-022-00233-0.

• DEARGs
• Immune infiltration
• Pathogenesis
• Psoriasis

OAS gene family plays an important role in antiviral process, but its role in pancreatic cancer has not yet been studied.

We analyzed the expression, prognostic value and biological function of the OAS gene family in human pancreatic cancer through comprehensive bioinformatic analysis and cellular level validation.

OAS family was highly expressed in pancreatic cancer, and this high expression significantly affected the clinical stage and prognosis of the tumor. OAS gene family was closely related to the immune infiltration of pancreatic cancer, especially neutrophils and dendritic cells, and many immune-related factors and pathways are enriched in the tumor, such as type I interferon signaling pathway and NOD-like receptor signaling pathway.

Taken together, high expression of OAS family is closely related to poor prognosis of pancreatic cancer. OAS gene family may serve as the biomarker and even therapeutic target of pancreatic cancer.

• OAS gene family
• biomarker
• immune infiltration
• pancreatic cancer
• prognosis

Psoriasis is a worldwide chronic inflammatory skin disease. The treatment of disease is usually designed according to its severity. In this research, RNA-seq was performed on 37 patients with psoriasis treated with guselkumab before and after treatment, and the patients were divided into fast responder and slow responder according to PASI score to analyze the differentially expressed genes (DEGs) between them. Moreover, The biological mechanism of psoriasis was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and Gene Set Enrichment Analysis (GSEA) analysis. And then, this protein-protein interaction network was constructed and 17 DEGs including IL-1β, CXCL8, S100A12 and MMP9 were analyzed by GSVA. DEGs were detected by GO and KEGG analysis of target genes, which were primarily associated with immune response, neutrophil activation, neutrophil degranulation. GSEA reminded that fast responders were mainly involved in low-density neutrophils and abundant NK cells. And the GSVA showed that the DEGs were down-regulated after the early stage of the fast responder and the reverse in the slow responder by GSVA analysis. On the whole, these results indicated that these DEGs may serve as a psoriasis potential diagnostic and predictive biomarkers after been treated by guselkumab.

• Antibodies, Monoclonal, Humanized/genetics
• Antibodies, Monoclonal, Humanized/therapeutic use
• Gene Expression
• Humans
• Neutrophils/metabolism
• Psoriasis/drug therapy
• Psoriasis/genetics
• Psoriasis/metabolism

• bioinformatics
• biomarkers
• cxcl10
• key genes
• psoriasis

• Biomarkers/metabolism
• Case-Control Studies
• Chemokine CXCL10/metabolism
• Computational Biology
• HaCaT Cells
• Humans
• Protein Interaction Maps
• Psoriasis/genetics
• Psoriasis/metabolism
• Skin/metabolism

Although more and more evidence has supported psoriasis is prone to atherosclerosis, the common mechanism of its occurrence is still not fully elucidated. The purpose of this study is to further explore the molecular mechanism of the occurrence of this complication.

The gene expression profiles of psoriasis (GSE30999) and atherosclerosis (GSE28829) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis and atherosclerosis, three kinds of analyses were performed, namely functional annotation, protein‐protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis.

A total of 94 common DEGs (24 downregulated genes and 70 upregulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. In addition, lipopolysaccharide-mediated signaling pathway is closely related to both. Finally, 16 important hub genes were identified using cytoHubba, including LYN, CSF2RB, IL1RN, RAC2, CCL5, IRF8, C1QB, MMP9, PLEK, PTPRC, FYB, BCL2A1, LCP2, CD53, NCF2 and TLR2.

Our study reveals the common pathogenesis of psoriasis and atherosclerosis. These common pathways and hub genes may provide new ideas for further mechanism research.

• atherosclerosis
• bioinformatics
• differentially expressed genes
• hub genes
• psoriasis