Key genes and immune infiltration in chronic spontaneous urticaria: a study of bioinformatics and systems biology.

Background: Chronic spontaneous urticaria (CSU) is defined by the spontaneous occurrence of wheals and/or angioedema for >6 weeks. The pathogenesis involves skin mast cells, but the complex causes of their activation remain to be characterized in detail. Objectives: To explore disease-driving genes and biological pathways in CSU. Methods: Two microarray data sets, e.g., GSE57178 and GSE72540, with mRNA information of skin from CSU patients, were downloaded from the Gene Expression Omnibus (GEO) database. An integrated bioinformatics pipeline including identification of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, co-expression and drug prediction analysis, and immune and stromal cells deconvolution analyses were applied to identify hub genes and key drivers of CSU pathogenesis. Results: In total, we identified 92 up-regulated and 7 down-regulated genes in CSU lesions. These were significantly enriched in CSU-related pathways such as TNF, NF-κB, and JAK-STAT signaling. Based on PPI network modeling, four genes, i.e., IL-6, TLR-4, ICAM-1, and PTGS-2, were computationally identified as key pathogenic players in CSU. Immune infiltration analyses indicated that dendritic cells, Th2 cells, mast cells, megakaryocyte-erythroid progenitor, preadipocytes, and M1 macrophages were increased in lesional CSU skin. Conclusion: Our results offer new insights on the pathogenesis of CSU and suggest that TNF, NF-κB, JAK-STAT, IL-6, TLR-4, ICAM-1, and PTGS-2 may be candidate targets for novel CSU treatments.

Screening and identification of the core immune-related genes and immune cell infiltration in severe burns and sepsis.

Severe burns often have a high mortality rate due to sepsis, but the genetic and immune crosstalk between them remains unclear. In the present study, the GSE77791 and GSE95233 datasets were analysed to identify immune-related differentially expressed genes (DEGs) involved in disease progression in both burns and sepsis. Subsequently, weighted gene coexpression network analysis (WGCNA), gene enrichment analysis, protein-protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, coexpression network analysis and clinical correlation analysis were performed. A total of 282 common DEGs associated with burns and sepsis were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the following enriched pathways in burns and sepsis: metabolic pathways; complement and coagulation cascades; legionellosis; starch and sucrose metabolism; and ferroptosis. Finally, six core DEGs were identified, namely, IL10, RETN, THBS1, FGF13, LCN2 and MMP9. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. Of these, RETN upregulation was associated with a worse prognosis. The immune-related genes and dysregulated immune cells in severe burns and sepsis provide potential research directions for diagnosis and treatment.

Therapeutic targets and signaling mechanisms of dasatinib activity against radiation skin ulcer.

Objective: To reveal the potential targets and signaling pathways of dasatinib in the treatment of radiation ulcers through network pharmacology and molecular docking technology. Methods: Pathological targets of radiation ulcers were screened using GeneCards database. At the same time, the pharmacological targets of dasatinib were obtained through SwissTargetPrediction (STP), Binding DB and Drugbank databases. Subsequently, the potential targets of dasatinib for anti-radiation ulcers were obtained after intersection by Venn diagram. Next, a protein-protein interaction (PPI) network was constructed through the STRING database and core targets were screened. Finally, the identified core targets were subjected to GO and KEGG enrichment analysis, co-expression network analysis, and molecular docking technology to verify the reliability of the core targets. Results: A total of 76 potential targets for anti-radiation ulcer with dasatinib were obtained, and 6 core targets were screened, including EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These genes were mainly enriched in Adherens junction, EGFR tyrosine kinase inhibitor resistance, Focal adhesion, Bladder cancer and PI3K-Akt signaling pathway. Molecular docking results showed that dasatinib binds well to the core target. Conclusion: Dasatinib may play a role in the treatment of radiation ulcers by regulating EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These core targets may provide new insights for follow-up studies of radiation ulcers.

Data-driven analysis to identify prognostic immune-related biomarkers in BRAF mutated cutaneous melanoma microenvironment.

Skin cutaneous melanoma is one of the deadly diseases, and more than 50% of the patients have BRAF gene mutations. Evidence suggests that oncogenic BRAF modulates the immune system's ability to recognize SKCM cells. Due to the complexity of the tumor microenvironment (TME) and a lack of a rational mechanistic basis, it is urgent to investigate the immune infiltration and identify prognostic biomarkers in BRAF mutated SKCM patients. Multiple methods including ESTIMATE algorithm, differential gene analysis, prognostic analysis and immune infiltration analysis were performed to investigate the tumor microenvironment. Based on the patient's immune score and stromal score, immune-related genes DEGs were identified. Functional analysis revealed that these genes were mainly enriched in biological processes such as immune response, defense response and positive regulation of immune system. Furthermore, we analyzed the immune infiltrating cell components of BRAF mutated patients and revealed 4 hub genes associated with overall survival time. Several cells (Monocyte, Macrophage and Gamma delta cells) have been found to be significantly decreased in immune-high BRAF mutated SKCM group. While CD4+T, CD8+T, CD4 naïve, Tr1, Th2 and many T cell subsets were significantly increased in immune-high group. These immune cells and genes were closely related to each other. This study revealed that the dysregulation of immune function and immune cells may contribute to the poor outcomes of BRAF mutated patients. It is of great significance to our further understanding of the TME and immune dysfunction in BRAF mutated SKCM.

Exploring the alterations and function of skin microbiome mediated by ionizing radiation injury.

Background: Radiation-induced skin injury (RISI) is still the most common and severe side effect of radiotherapy. The role of the skin's microbial barrier in the pathogenesis and progression of RISI needs to be fully investigated. Methods: This study aimed to explore the alterations in and functions of the skin microbiota in RISI. We applied the unculturable approach to characterize the cutaneous microbiomes of a radiation-induced animal model by sequencing the V1-V3 regions of the 16S ribosomal RNA (rRNA) gene. Combined with the downloaded clinical data of patients, a comprehensive analysis was performed to identify potential radioprotective species and metabolic pathways. Results: There were no significant differences in the alpha diversity indices (Sobs, Shannon, Simpson, Ace, and Chao) between the acute radiation injury and control groups. Phylum-level analysis of the RISI microbiomes exhibited significant predominance of Firmicutes (mean abundance = 67%, corrected p = 0.0035). The high abundance of Firmicutes was significantly associated with rapid healing of RISI (average relative abundance = 52%; Kruskal-Wallis: p = 5.7E-4). Among its members, Streptococcus, Staphylococcus, Acetivibrio ethanolgignens group, Peptostreptococcus, Anaerofilum, and UCG-002 [linear discriminant analysis (LDA) > 3, p < 0.05] were identified as the core genera of Firmicutes. In addition, Lachnosiraceae and Lactobacillus occupied an important position in the interaction network (r > 0.6, p < 0.05). The differential metabolic pathways of RISI were mainly associated with carbohydrate metabolism (butanoate and propanoate metabolism), amino acid metabolism (tryptophan and histidine metabolism), energy metabolism, and lipid metabolism (fatty acid degradation and biosynthesis). Conclusion: This study provides new insights into the potential mechanism and skin microbial changes in the progression of RISI. The overwhelming predominance of members of Firmicutes, including Streptococcaceae, Staphylococcaceae, Lachnospiraceae, and Lactobacillus, is potentially related to rapid healing of RISI. The microbiota-metabolite axis plays a critical role in RISI and provides promising therapeutic targets for the treatment of adverse side effects.

Mechanisms underlying the therapeutic effects of 4-octyl itaconate in treating sepsis based on network pharmacology and molecular docking.

Objective: Through network pharmacology and molecular docking technology, the hub genes, biological functions, and signaling pathways of 4-Octyl itaconate (4-OI) against sepsis were revealed. Methods: Pathological targets of sepsis were screened using GeneCards and GEO databases. Similarly, the pharmacological targets of 4-OI were obtained through Swiss TargetPrediction (STP), Similarity ensemble approach (SEA), and TargetNet databases. Then, all the potential targets of 4-OI anti-sepsis were screened by the online platform Draw Venn diagram, and the hub genes were screened by Cytoscape software. The identified hub genes were analyzed by GO and KEGG enrichment analysis, protein interaction (PPI) network, and molecular and docking technology to verify the reliability of hub gene prediction, further confirming the target and mechanism of 4-OI in the treatment of sepsis. Results: After the target screening of 4-OI and sepsis, 264 pharmacological targets, 1953 pathological targets, and 72 genes related to 4-OI anti-sepsis were obtained, and eight hub genes were screened, namely MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2, and HSP90AA1. The enrichment analysis results indicated that 4-OI might be involved in regulating inflammatory imbalance, immunosuppression, and oxidative stress in developing sepsis. 4-OI protects multiple organ dysfunction in sepsis by acting on hub genes, and MMP9 is a reliable gene for the prognosis and diagnosis of sepsis. The molecular docking results showed that 4-OI binds well to the hub target of sepsis. Conclusion: 4-OI plays an antiseptic role by regulating MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2 and HSP90AA1. These Hub genes may provide new insights into follow-up research on the target of sepsis treatment.

WDR43 is a potential diagnostic biomarker and therapeutic target for osteoarthritis complicated with Parkinson's disease.

Osteoarthritis (OA) and Parkinson's disease (PD) are on the rise and greatly impact the quality of individuals' lives. Although accumulating evidence indicates a relationship between OA and PD, the particular interactions connecting the two diseases have not been thoroughly examined. Therefore, this study explored the association through genetic characterization and functional enrichment. Four datasets (GSE55235, GSE12021, GSE7621, and GSE42966) were chosen for assessment and validation from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was implemented to determine the most relevant genes for clinical features. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to explore the biological processes of common genes, and to display the interrelationships between common genes, the STRING database and the application Molecular Complex Detection Algorithm (MCODE) of Cytoscape software were leveraged to get hub genes. By intersecting the common genes with the differentially expressed genes (DEGs) acquired from GSE12021 and GSE42966, the hub genes were identified. Finally, we validated the diagnostic efficacy of hub genes and explored their correlation with 22 immune infiltrating cells. As a consequence, we discovered 71 common genes, most of which were functionally enriched in antigen processing and presentation, mitochondrial translation, the mRNA surveillance pathway, and nucleocytoplasmic transport. Furthermore, WDR43 was found by intersecting eight hub genes with 28 DEGs from the two validation datasets. Receiver Operating Characteristic (ROC) implied the diagnostic role of WDR43 in OA and PD. Immune infiltration research revealed that T-cell regulatory (Tregs), monocytes, and mast cells resting were associated with the pathogenesis of OA and PD. WDR43 may provide key insights into the relationship between OA and PD.

Genetic and immune crosstalk between severe burns and blunt trauma: A study of transcriptomic data.

Background: Severe burns and blunt trauma can lead to multiple organ dysfunction syndrome, the leading cause of death in intensive care units. In addition to infection, the degree of immune inflammatory response also affects prognosis. However, the characteristics and clinical relevance of the common mechanisms of these major diseases are still underexplored. Methods: In the present study, we performed microarray data analysis to identify immune-related differentially expressed genes (DEGs) involved in both disease progression in burns and blunt trauma. Six analyses were subsequently performed, including gene enrichment analysis, protein-protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, co-expression network analysis, and clinical correlation analysis. Results: A total of 117 common immune-related DEGs was selected for subsequent analyses. Functional analysis emphasizes the important role of Th17 cell differentiation, Th1 and Th2 cell differentiation, Cytokine-cytokine receptor interaction and T cell receptor signaling pathway in these two diseases. Finally, eight core DEGs were identified using cytoHubba, including CD8A, IL10, CCL5, CD28, LCK, CCL4, IL2RB, and STAT1. The correlation analysis showed that the identified core DEGs were more or less significantly associated with simultaneous dysregulation of immune cells in blunt trauma and sepsis patients. Of these, the downregulation of CD8A and CD28 had a worse prognosis. Conclusion: Our analysis lays the groundwork for future studies to elucidate molecular mechanisms shared in burns and blunt trauma. The functional roles of identified core immune-related DEGs and dysregulated immune cell subsets warrant further in-depth study.

Exploring Potential Biomarkers, Ferroptosis Mechanisms, and Therapeutic Targets Associated with Cutaneous Squamous Cell Carcinoma via Integrated Transcriptomic Analysis.

Background: Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with nonmelanoma skin cancers (NMSC). However, the unclear pathogenesis of cSCC limits the application of molecular targeted therapy. Methods: Three microarray datasets (GSE2503, GSE45164, and GSE66359) were downloaded from the Gene Expression Omnibus (GEO). After identifying the differentially expressed genes (DEGs) in tumor and nontumor tissues, five kinds of analyses, namely, functional annotation, protein-protein interaction (PPI) network, hub gene selection, TF-miRNA-mRNA regulatory network analysis, and ferroptosis mechanism, were performed. Results: A total of 146 DEGs were identified with significant differences, including 113 upregulated genes and 33 downregulated genes. The enriched functions and pathways of the DEGs included microtubule-based movement, ATP binding, cell cycle, P53 signaling pathway, oocyte meiosis, and PLK1 signaling events. Nine hub genes were identified (CDK1, AURKA, RRM2, CENPE, CCNB1, KIAA0101, ZWINT, TOP2A, and ASPM). Finally, RRM2, AURKA, and SAT1 were identified as significant ferroptosis-related genes in cSCC. The differential expression of these genes has been verified in two other independent datasets. Conclusions: By integrated bioinformatic analysis, the hub genes identified in this study elucidated the molecular mechanism of the pathogenesis and progression of cSCC and are expected to become future biomarkers or therapeutic targets.

The commonness in immune infiltration of rheumatoid arthritis and atherosclerosis: Screening for central targets via microarray data analysis.

Background: Although increasing evidence has reported an increased risk of atherosclerosis (AS) in rheumatoid arthritis (RA), the communal molecular mechanism of this phenomenon is still far from being fully elucidated. Hence, this article aimed to explore the pathogenesis of RA complicated with AS. Methods: Based on the strict inclusion/exclusion criteria, four gene datasets were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the communal differentially expressed genes (DEGs) and hub genes, comprehensive bioinformatics analysis, including functional annotation, co-expression analysis, expression validation, drug-gene prediction, and TF-mRNA-miRNA regulatory network construction, was conducted. Moreover, the immune infiltration of RA and AS was analyzed and compared based on the CIBERSORT algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in RA and AS respectively. Results: A total of 54 upregulated and 12 downregulated communal DEGs were screened between GSE100927 and GSE55457, and functional analysis of these genes indicated that the potential pathogenesis lies in immune terms. After the protein-protein interaction (PPI) network construction, a total of six hub genes (CCR5, CCR7, IL7R, PTPRC, CD2, and CD3D) were determined as hub genes, and the subsequent comprehensive bioinformatics analysis of the hub genes re-emphasized the importance of the immune system in RA and AS. Additionally, three overlapping infiltrating immune cells were found between RA and AS based on the CIBERSORT algorithm, including upregulated memory B cells, follicular helper T cells and γδT cells. Conclusions: Our study uncover the communal central genes and commonness in immune infiltration between RA and AS, and the analysis of six hub genes and three immune cells profile might provide new insights into potential pathogenesis therapeutic direction of RA complicated with AS.

Data mining reveal the association between diabetic foot ulcer and peripheral artery disease.

Background: Diabetic foot ulcer (DFU) and peripheral artery disease (PAD) are common diseases that seriously affect the quality of life and bring a huge economic burden to society. Although mounting evidence supports a close link between the two disorders, the mechanisms of comorbidity remain to be fully elucidated. Methods: The gene expression profiles of DFU (GSE80178) and PAD (GSE100927) were downloaded from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) performed pathway enrichment analysis for common differentially expressed genes (DEGs) present in DFU and PAD. Subsequently, we constructed a protein-protein interaction (PPI) network using the STRING database and detected core modules and hub genes in the network. Finally, we analyzed the co-expression network and the TF-miRNA-mRNA regulatory network of hub genes. Results: A total of 167 common DEGs (91 up-regulated genes and 76 down-regulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. Finally, six hub genes were identified using cytoHubba, including CXCL8, IL1RN, MMP1, CD68, CCR7 and CCL3. Conclusions: The hub genes and signaling pathways involved can regulate both diseases simultaneously, suggesting a close relationship between the molecular mechanisms of the two diseases and possible targets for drugs that intervene in both diseases.

Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3.

Background: Atopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (TH) 2/TH22polarization and cytokines.Galectin-9 (Gal-9), via its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote TH2/TH22 immunity. The relevance of this in AD is largely unclear. Objectives: To characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms. Methods: We assessed the expression of Gal-9 and TIM-3 in 30 AD patients, to compare them with those of 30 healthy controls (HC) and to explore possible links with disease features including AD activity (SCORAD), IgE levels, and circulating eosinophils and B cells. We also determined the effects of Gal-9 on T cells from the AD patients. Results: Our AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing TH1 and TH17 cells than HC. Gal-9 and TIM-3 were linked to high disease activity, IgE levels, and circulating eosinophils and/or B cells. The rates of circulating TIM-3-positive CD4+ cells were positively correlated with rates of TH2/TH22 cells and negatively correlated with rates of TH1/TH17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD. Conclusion: Our findings suggest thatGal-9, via TIM-3, contributes to the pathogenesis of AD by augmenting TH2/TH22 polarization through the downregulation of TH1/TH17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment.

Application of the Jigsaw Puzzle Flap Based on Freestyle Perforators to Repair Large and Deep Ulcers on the Buttocks.

Background: Decubitus ulcers are common skin injuries in plastic and burn surgery departments, usually occur in patients with a long disease course and poor underlying health. Designing a reconstruction procedure with safety blood supply to a large volume soft tissue and resulting in minimal trauma is a priority for surgeons. Methods: The free-style perforators on the potential donor sites surrounding the ulcers were detected by Doppler, and the area of the ulcer was divided into several sections based on the location of pre-design perforator flaps. According to the insertion point of the perforators, small V-Y advancement flaps, propeller flaps and rotation flaps pedicled with freestyle perforators were formed and moderately modified during surgery. All of the small flaps were transplanted from donor sites to the defect and reassembled into a new composite flap to repair the ulcer. The donor sites were directly closed. The area of the flaps ranged from 7.0 × 10.5 cm to 8.0 × 22.0 cm and the diameter of the pedicle perforators ranged from 0.5 to 4.0 mm. Results: In 30 patients, 65 flaps were constructed, and all of the flaps survived with direct closure of all donor sites. One case with effusion healed 1 month postoperatively through draining and application of a mild pressure dressing. After a 3-24 months follow-up period, all of the patients were satisfied with post-operative function and appearance, and only one case had a local recurrence 6 months postoperatively. Conclusion: The jigsaw puzzle flap based on freestyle perforators can repair the large skin and soft tissue defects caused by decubitus ulcers on the buttocks, with direct donor flap area closure. This method is easy to perform with a safe blood supply and minimal trauma resulting from the avoidance of microvascular anastomosis and the conventional myocutaneous flap.

Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis.

Background: Cardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis. Methods: Six datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)-mRNA-microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM. Results: We found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM. Conclusion: The identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

Exploration of comorbidity mechanisms and potential therapeutic targets of rheumatoid arthritis and pigmented villonodular synovitis using machine learning and bioinformatics analysis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Pigmented villonodular synovitis (PVNS) is a tenosynovial giant cell tumor that can involve joints. The mechanisms of co-morbidity between the two diseases have not been thoroughly explored. Therefore, this study focused on investigating the functions, immunological differences, and potential therapeutic targets of common genes between RA and PVNS. Methods: Through the dataset GSE3698 obtained from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) were screened by R software, and weighted gene coexpression network analysis (WGCNA) was performed to discover the modules most relevant to the clinical features. The common genes between the two diseases were identified. The molecular functions and biological processes of the common genes were analyzed. The protein-protein interaction (PPI) network was constructed using the STRING database, and the results were visualized in Cytoscape software. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression and random forest (RF) were utilized to identify hub genes and predict the diagnostic efficiency of hub genes as well as the correlation between immune infiltrating cells. Results: We obtained a total of 107 DEGs, a module (containing 250 genes) with the highest correlation with clinical characteristics, and 36 common genes after taking the intersection. Moreover, using two machine learning algorithms, we identified three hub genes (PLIN, PPAP2A, and TYROBP) between RA and PVNS and demonstrated good diagnostic performance using ROC curve and nomogram plots. Single sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the biological functions in which three genes were mostly engaged. Finally, three hub genes showed a substantial association with 28 immune infiltrating cells. Conclusion: PLIN, PPAP2A, and TYROBP may influence RA and PVNS by modulating immunity and contribute to the diagnosis and therapy of the two diseases.

Exploring the Pathogenesis of Psoriasis Complicated With Atherosclerosis via Microarray Data Analysis.

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

Identification of Hub Genes and Immune Infiltration in Psoriasis by Bioinformatics Method.

BACKGROUND: Psoriasis is a chronic, prolonged, and recurrent skin inflammatory disease. However, the pathogenesis of psoriasis is not completely clear, thus we aimed to explore potential molecular basis of it. METHODS: Two datasets were downloaded from the Gene Expression Omnibus database. After identifying the differentially expressed genes of psoriasis skin lesion samples and healthy controls, three kinds of analyses, namely functional annotation, protein-protein interaction (PPI) network, and immune infiltration analyses, were performed. RESULTS: A total of 152 up-regulated genes and 38 down-regulated genes were selected for subsequent analyses. Evaluation of the PPI network identified the most important module containing 13 hub genes. Gene ontology analysis showed that the hub genes have a significant enrichment effect on positive regulation of cell migration, defense response to the other organism and epithelial cell differentiation. KEGG signaling pathway analysis showed that the hub genes were significantly enriched in chemokine signaling, Toll-like receptor signaling pathway, and IL-17 signaling pathway. Compared with the normal control sample, naive B cells, CD8+ T cells, activated memory CD4+ T cells, follicular helper T cells, gamma delta T cells, resting NK cells, monocytes, M0 macrophages, M1 macrophages, activated dendritic cells and neutrophils infiltrated more, while memory B cells, naive CD4+ T cells, regulatory T cells (Tregs), activated NK cells, resting mast cells, and eosinophils infiltrated less. CONCLUSION: To conclude, the hub genes and pathways identified from psoriasis lesions and normal controls along with the immune infiltration profile may provide new insights into the study of psoriasis.

Bioinformatic analysis reveals hub genes and pathways that promote melanoma metastasis.

BACKGROUND: Melanoma has the highest mortality rate of all skin tumors, and metastases are the major cause of death from it. The molecular mechanism leading to melanoma metastasis is currently unclear. METHODS: With the goal of revealing the underlying mechanism, three data sets with accession numbers GSE8401, GSE46517 and GSE7956 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed gene (DEG) of primary melanoma and metastatic melanoma, three kinds of analyses were performed, namely functional annotation, protein-protein interaction (PPI) network and module construction, and co-expression and drug-gene interaction prediction analysis. RESULTS: A total of 41 up-regulated genes and 79 down-regulated genes was selected for subsequent analyses. Results of pathway enrichment analysis showed that extracellular matrix organization and proteoglycans in cancer are closely related to melanoma metastasis. In addition, seven pivotal genes were identified from PPI network, including CXCL8, THBS1, COL3A1, TIMP3, KIT, DCN, and IGFBP5, which have all been verified in the TCGA database and clinical specimens, but only CXCL8, THBS1 and KIT had significant differences in expression. CONCLUSIONS: To conclude, CXCL8, THBS1 and KIT may be the hub genes in the metastasis of melanoma and thus may be regarded as therapeutic targets in the future.

Comparisons of pollution characteristics, emission situations, and mass loads for heavy metals in the manures of different livestock and poultry in China.

The application of livestock and poultry manures was the predominant source of heavy metals in agricultural soils, particularly in China. It is important to systematically compare the pollution characteristics, emission situations and mass loads for heavy metals in the manures of different livestock and poultry in China. According to analysis and estimation based on the reported concentration levels of eight heavy metals (Zn, Cu, Pb, Cd, Cr, Hg, As, and Ni) and the feed quantities of livestock (pig, cattle, and sheep) and poultry in 2017, the concentrations of Zn and Cu and the over-standard frequencies of Zn, Cu, Cd, and As were much higher than those of other heavy metals, especially in pig manure. In 2017, the total emission of livestock and poultry manure in China was 1.64 × 109 t (FW), which was mainly excreted from cattle (45.77%); while the total emission of heavy metals sourced from manures was 2.86 × 105 t (DW), with the predominant contribution originating from pig manure (71.52%). The highest mass loads of manures and heavy metals were observed in Shandong, Tianjin, Henan, and Shanghai, where heavy metal contamination may be occurring (especially for Zn and Cu). The heavy metal concentrations in livestock and poultry manures of China were similar to other countries; however, more heavy metals were discharged into agricultural land through manure (especially for Zn and Cu). For many countries, abundant Zn and Cu exist in agricultural soils, principally contributed by livestock and poultry manures. These heavy metals originate from their addition to livestock and poultry feeds. Therefore, reducing the addition of Zn and Cu in feeds is an effective measure to lower their input into agricultural soils.