Analysis Of The Co-morbidity Mechanism And Prescriptions Of Psoriasis Vulgaris And Metabolic Syndrome Based On Bioinformatic

Background:There is a close relationship between psoriasis and metabolic syndrome,but the biological mechanisms underlying the comorbidity of psoriasis and metabolic syndrome are not fully understood.Traditional Chinese medicine(TCM)treatment has been shown to have a definite effect on improving psoriatic skin lesions and metabolic parameters in comorbid patients,but there is currently limited clinical research on TCM treatment for the comorbidity of psoriasis and metabolic syndrome,making it difficult to explore prescription patterns and pharmacological mechanisms through data mining.Objective:To investigate the comorbidity mechanism,traditional Chinese medicine prescription patterns,and potential pharmacological mechanisms of psoriasis and metabolic syndrome.Methods:1 Downloading GSE117239,GSE117468 and GSE136757 microarray datasets from GEO database as psoriasis vulgaris(hereinafter referred to as psoriasis)training set,GSE30999 microarray dataset as psoriasis validation set and GSE98895 microarray dataset as metabolic syndrome validation set;2 Differential analysis was performed on the samples of the psoriasis training set with|logFC|>1 and corrected P-value<0.05 to obtain the differential genes for psoriasis.Obtaining DisGeNETdifferential genes for metabolic syndrome from GeneCards,OMIM,and databases,and obtaining co-morbidity genes for multiple enrichment analysis after taking the intersection of the two;3 The characteristic crosstalk genes were screened by LASSO regression model and random forest tree model,and the genes with area under the ROC curve value>0.7 were selected for validation in two validation sets,respectively.Differential analysis of immune cell infiltration between psoriasis lesion samples and control samples using CIBERSORT and ssGSEA method,and correlation analysis of the screened characteristic co-morbid genes with immune cell infiltration;4 Analysis of the characteristic co-disease genes with PASI values and response after the use of biological agents;5 Collecting relevant literature on the use of Chinese herbal medicine for the treatment of psoriasis and metabolic syndrome through CNKI,Wanfang database,Chinese Biomedical Literature Database and VIP Datebase,respectively,for screening and prescription data normalization;6 Using the TCM Inheritage auxiliary platform(V3.0),drug frequency statistics,Siqi and Wu Wei attribution analysis,association analysis and cluster analysis were conducted.Taking the top 15%of drug frequencies for the treatment of psoriasis and metabolic syndrome to obtain the intersecting drugs;7 The active ingredients and targets of the intersecting drugs were obtained through the systemic pharmacology database of traditional Chinese medicine,BATMAN-TCM database and combined with literature research based on the screening conditions of oral bioavailability≥30%and drug-like properties≥0.18.The drug targets and co-disease genes were taken to intersect to obtain the intersecting targets.Using Cytoscape 3.9.2 software,construct"component-target-disease" network and protein-protein interaction network(PPI),and perform network topology analysis,and screen the top 10 core targets according to Degree value;8 Correlation analysis of gene expression of core targets with immune cell content to investigate their effect on immune cell infiltration.Molecular docking of the top 6 degree values and core targets and the top 2 ranked macromolecules in the PPI network was performed using the Autodock program to evaluate their binding ability;9 GO and KEGG enrichment analysis of the intersecting target genes was performed using R software to investigate the pathways of action of intersecting drugs for the treatment of psoriasis and metabolic syndrome co-morbidities.Results:1 A total of 802 co-morbid genes of psoriasis and metabolic syndrome were obtained,mainly enriched in gene sets related to cell division,immune inflammation and metabolism;2 Five characteristic co-morbid genes,NLRX1,KYNU,ABCC1,BTC,SERPINB4,were screened based on two machine learning algorithms,among which NLRX1 passed validation;3 The infiltration of multiple immune cells in psoriatic lesions and non-lesions differed and correlated with NLRX1;4 The expression of NLRX1 showed a threshold saturation effect with psoriasis PASI score.NLRX1 expression and PASI values were predictive of response or non-response after the use of biologics.5 A total of 322 TCM prescriptions involving 256 herbal medicines for psoriasis and 172 TCM prescriptions involving 200 herbal medicines for metabolic syndrome were collected.The efficacy of the drugs for the treatment of psoriasis and metabolic syndrome were all based on Heat-clearing,restore deficiency,Promoting blood circulation and removing blood stasis,Diaphoresis,and Inducing diuresis and Excreting dampness;the four natures of the drugs were all based on cold,calm and warm;the five flvors were all based on bitter and sweet;and the generalized meridians were all based on liver,heart,lung and spleen meridians;6 The co-morbid intersection drugs for the treatment of psoriasis and metabolic syndrome are:Di Huang,Dan Shen,Gan Cao,Chuan Xiong,Chi Shao,Fu Ling,Shu Dihuang,Huang Qin,Huang Qi,and Bai Shao.Network pharmacological analysis of co-disease genes and codisease intersecting drugs yielded 39 intersecting targets with co-disease genes and 13 active ingredients,among which IL1B,CXCL8,MYC,STAT3,EGF,MMP9,CCL2,PPARG,HMOX1,STAT1 were the core targets and the core targets were related to psoriasis immune cell infiltration;7 Molecular docking results showed that the degree-ranked top 6 targets IL1B,CXCL8,MYC,STAT3,EGF,MMP9 have good binding activity with the degree-ranked top 2 active ingredients quercetin and kaempferol;8 Intersectional target genes were mainly enriched in angiogenesis,cell proliferation and inflammation related gene sets as well as some disease pathways.Conclusion:The co-morbidity of psoriasis and metabolic syndrome is related to various factors such as inflammation and metabolism,and NLRX1 can be used as a characteristic comorbidity gene of psoriasis and metabolic syndrome with some clinical significance.The TCM treatment of psoriasis and metabolic syndrome co-morbidity can be started from liver,spleen and heart,using drugs such as Di Huang,Dan Shen,Gan Cao,Chuan Xiong,Chi Shao,Fu Ling,Shu Di Huang,Huang Qin,Huang Qi and Bai Shao,which may act on pathways related to angiogenesis,cell proliferation and immune inflammation through active ingredients such as quercetin and kaempferol.