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  1. Article ; Online: IFI44 is an immune evasion biomarker for SARS-CoV-2 and

    Zheng, Qingcong / Wang, Du / Lin, Rongjie / Lv, Qi / Wang, Wanming

    Frontiers in immunology

    2022  Volume 13, Page(s) 1013322

    Abstract: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19). : Methods: The RA dataset (GSE93272) and the : Results: A total of 199 DEGs were extracted from the ... ...

    Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe coronavirus disease 2019 (COVID-19).
    Methods: The RA dataset (GSE93272) and the
    Results: A total of 199 DEGs were extracted from the GSE93272 and GSE33341 datasets. KEGG analysis of enrichment pathways were NLR signaling pathway, cell membrane DNA sensing pathway, oxidative phosphorylation, and viral infection. Positive/negative regulation of the immune system, regulation of the interferon-I (IFN-I; IFN-α/β) pathway, and associated pathways of the immunological response to viruses were enriched in GO and ClueGO analyses. PPI network and Cytoscape platform identified the top 10 hub genes: RSAD2, IFIT3, GBP1, RTP4, IFI44, OAS1, IFI44L, ISG15, HERC5, and IFIT5. The pathways are mainly enriched in response to viral and bacterial infection, IFN signaling, and 1,25-dihydroxy vitamin D3. IFI44, OAS1, IFI44L, ISG15, and HERC5 are the five hub genes shared by RA, COVID-19, and SAB. The pathways are primarily enriched for response to viral and bacterial infections. The TF-hub gene network and miRNA-hub gene network identified YY1 as a key TF and hsa-mir-1-3p and hsa-mir-146a-5p as two important miRNAs related to IFI44. IFI44 was identified as a hub gene by validating GSE17755, GSE55235, and GSE13670. Immune cell infiltration analysis showed a strong positive correlation between activated dendritic cells and IFI44 expression.
    Conclusions: IFI144 was discovered as a shared biomarker and disease target for RA, COVID-19, and SAB by this study. IFI44 negatively regulates the IFN signaling pathway to promote viral replication and bacterial proliferation and is an important molecular target for SARS-CoV-2 and
    MeSH term(s) Antigens ; Arthritis, Rheumatoid/genetics ; Biomarkers ; COVID-19/genetics ; Cholecalciferol ; Cytoskeletal Proteins ; Humans ; Immune Evasion ; Interferons ; MicroRNAs/genetics ; SARS-CoV-2 ; Staphylococcal Infections ; Staphylococcus aureus/metabolism
    Chemical Substances Antigens ; Biomarkers ; Cytoskeletal Proteins ; IFI44 protein, human ; MicroRNAs ; Cholecalciferol (1C6V77QF41) ; Interferons (9008-11-1)
    Language English
    Publishing date 2022-09-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1013322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Quercetin is a Potential Therapy for Rheumatoid Arthritis via Targeting Caspase-8 Through Ferroptosis and Pyroptosis.

    Zheng, Qingcong / Wang, Du / Lin, Rongjie / Chen, Yuchao / Xu, Zixing / Xu, Weihong

    Journal of inflammation research

    2023  Volume 16, Page(s) 5729–5754

    Abstract: Background: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases. However, the underlying molecular mechanisms of its pathogenesis are unknown. This study aimed to identify the common biomarkers of ferroptosis and ...

    Abstract Background: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases. However, the underlying molecular mechanisms of its pathogenesis are unknown. This study aimed to identify the common biomarkers of ferroptosis and pyroptosis in RA and screen potential drugs.
    Methods: The RA-related differentially expressed genes (DEGs) in GSE55235 were screened by R software and intersected with ferroptosis and pyroptosis gene libraries to obtain differentially expressed ferroptosis-related genes (DEFRGs) and differentially expressed pyroptosis-related genes (DEPRGs). We performed Gene Ontology (GO), Kyoto Encyclopedia of the Genome (KEGG), ClueGO, and Protein-Protein Interaction (PPI) analysis for DEFRGs and DEPRGs and validated them by machine learning. The microRNA/transcription factor (TF)-hub genes regulatory network was further constructed. The key gene was validated using the GSE77298 validation set, cellular validation was performed in in vitro experiments, and immune infiltration analysis was performed using CIBERSORT. Network pharmacology was used to find key gene-targeting drugs, followed by molecular docking and molecular dynamics simulations to analyze the binding stability between small-molecule drugs and large-molecule proteins.
    Results: Three hub genes (CASP8, PTGS2, and JUN) were screened via bioinformatics, and the key gene (CASP8) was validated and obtained through the validation set, and the diagnostic efficacy was verified to be excellent through the receiver operating characteristic (ROC) curves. The ferroptosis and pyroptosis phenotypes were constructed by fibroblast-like synoviocytes (FLS), and caspase-8 was detected and validated as a common biomarker for ferroptosis and pyroptosis in RA, and quercetin can reduce caspase-8 levels. Quercetin was found to be a potential target drug for caspase-8 by network pharmacology, and the stability of their binding was further verified using molecular docking and molecular dynamics simulations.
    Conclusion: Caspase-8 is an important biomarker for ferroptosis and pyroptosis in RA, and quercetin is a potential therapy for RA via targeting caspase-8 through ferroptosis and pyroptosis.
    Language English
    Publishing date 2023-12-01
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2494878-0
    ISSN 1178-7031
    ISSN 1178-7031
    DOI 10.2147/JIR.S439494
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Identification of Important Modules and Biomarkers That Are Related to Immune Infiltration Cells in Severe Burns Based on Weighted Gene Co-Expression Network Analysis.

    Zhang, Zexin / He, Yan / Lin, Rongjie / Lan, Junhong / Fan, Yueying / Wang, Peng / Jia, Chiyu

    Frontiers in genetics

    2022  Volume 13, Page(s) 908510

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2022-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2022.908510
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis.

    Zheng, Qingcong / Wang, Du / Lin, Rongjie / Chen, Yuchao / Huang, Haoen / Xu, Zixing / Zheng, Chunfu / Xu, Weihong

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1299122

    Abstract: Background: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus ...

    Abstract Background: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.
    Methods: The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.
    Results: In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154;
    Conclusion: According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.
    Language English
    Publishing date 2023-12-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1299122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Osteopontin induces atrial fibrosis by activating Akt/GSK-3β/β-catenin pathway and suppressing autophagy.

    Lin, Rongjie / Wu, Shaohui / Zhu, Dan / Qin, Mu / Liu, Xu

    Life sciences

    2020  Volume 245, Page(s) 117328

    Abstract: Aims: Atrial fibrosis is a common feature of atrial fibrillation (AF). Recently, it is reported that osteopontin (OPN) can induce fibrosis in lungs, livers and kidneys. However, its role in atrial fibrosis remains unclear. Here, we sought to determine ... ...

    Abstract Aims: Atrial fibrosis is a common feature of atrial fibrillation (AF). Recently, it is reported that osteopontin (OPN) can induce fibrosis in lungs, livers and kidneys. However, its role in atrial fibrosis remains unclear. Here, we sought to determine the involvement of OPN in atrial fibrosis and the underlying mechanisms during this pathological remodeling process.
    Materials and methods: Protein expressions were determined by enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining and immunoblotting. mRNA expressions were detected by qRT-PCR. Cell proliferation was assessed by CCK-8. Left atrial electroanatomical voltage maps were created using PentaRay catheters and a 3-dimensional mapping system.
    Key findings: OPN was highly expressed in the circulation of AF patients and was further increased with the progression of AF. In addition, correlation analysis showed that circulating OPN positively related with low-voltage areas (LVAs, a marker of atrial fibrosis) in AF patients. Immunohistological staining and immunoblotting revealed an increased expression of OPN in AF patients who present a higher degree of atrial fibrosis. Furthermore, in vitro studies in cultured human atrial fibroblasts (hAFs) demonstrated that OPN promoted the proliferation of fibroblasts and increased production of collagen I and fibronectin. Mechanistically, the profibrotic effects of OPN on atrial fibroblasts were determined via activating Akt/GSK-3β/β-catenin signaling and suppressing autophagy.
    Significance: This study uncovered a previously unrecognized profibrotic role of OPN in atrial fibrosis, which was achieved through activation of Akt/GSK-3β/β-catenin signaling pathway and suppression of autophagy, implying a promising therapeutic target in atrial fibrosis and AF.
    MeSH term(s) Aged ; Atrial Fibrillation/metabolism ; Atrial Fibrillation/pathology ; Autophagy/physiology ; Case-Control Studies ; Collagen/metabolism ; Female ; Fibronectins/metabolism ; Fibrosis ; Glycogen Synthase Kinase 3 beta/metabolism ; Heart Atria/metabolism ; Heart Atria/pathology ; Humans ; Male ; Middle Aged ; Osteopontin/physiology ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/physiology ; beta Catenin/metabolism
    Chemical Substances Fibronectins ; SPP1 protein, human ; beta Catenin ; Osteopontin (106441-73-0) ; Collagen (9007-34-5) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2020-01-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2020.117328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Combining a CDK4/6 Inhibitor With Pemetrexed Inhibits Cell Proliferation and Metastasis in Human Lung Adenocarcinoma.

    Ke, Yuan / Liao, Cheng-Gong / Zhao, Zheng-Qing / Li, Xiao-Min / Lin, Rong-Jie / Yang, Long / Zhang, He-Long / Kong, Ling-Min

    Frontiers in oncology

    2022  Volume 12, Page(s) 880153

    Abstract: Background: Recent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about ... ...

    Abstract Background: Recent clinical trials of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in human lung adenocarcinoma (LUAD) have not achieved satisfactory results. The disappointing results of single-drug treatments have prompted studies about synergistic therapies of CDK4/6i with other drugs. We aimed to test the anti-tumor effect of ribociclib (a CDK4/6i) combined with pemetrexed on LUAD and the potential mechanisms.
    Methods: Cell lines were exposed to ribociclib and pemetrexed at different doses. Antitumor effects were measured using growth inhibition. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Cell migration and invasion were measured using wound healing and transwell invasion assays, respectively. The expression levels of proteins were analyzed using western blotting. Mice xenograft models were used for validation
    Results: Synergism was associated with a combination of cell cycle effects from both agents. Cell cycle analysis revealed that pemetrexed blocked cells in the S phase, whereas ribociclib arrested cells in the G1 phase. Concomitant treatment with pemetrexed and ribociclib resulted in a significantly stronger antitumor ability than treatment alone. We also found that ribociclib strongly enhanced the pro-apoptotic activity of pemetrexed
    Conclusions: Combining ribociclib and pemetrexed showed a powerful ability to inhibit cancer proliferation, invasion, and metastasis, and it holds potential as a novel effective combinative therapy for patients with LUAD.
    Language English
    Publishing date 2022-05-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.880153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Osteopontin induces atrial fibrosis by activating Akt/GSK-3β/β-catenin pathway and suppressing autophagy

    Lin, Rongjie / Wu, Shaohui / Zhu, Dan / Qin, Mu / Liu, Xu

    Life sciences. 2020 Mar. 15, v. 245

    2020  

    Abstract: Atrial fibrosis is a common feature of atrial fibrillation (AF). Recently, it is reported that osteopontin (OPN) can induce fibrosis in lungs, livers and kidneys. However, its role in atrial fibrosis remains unclear. Here, we sought to determine the ... ...

    Abstract Atrial fibrosis is a common feature of atrial fibrillation (AF). Recently, it is reported that osteopontin (OPN) can induce fibrosis in lungs, livers and kidneys. However, its role in atrial fibrosis remains unclear. Here, we sought to determine the involvement of OPN in atrial fibrosis and the underlying mechanisms during this pathological remodeling process.Protein expressions were determined by enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining and immunoblotting. mRNA expressions were detected by qRT-PCR. Cell proliferation was assessed by CCK-8. Left atrial electroanatomical voltage maps were created using PentaRay catheters and a 3-dimensional mapping system.OPN was highly expressed in the circulation of AF patients and was further increased with the progression of AF. In addition, correlation analysis showed that circulating OPN positively related with low-voltage areas (LVAs, a marker of atrial fibrosis) in AF patients. Immunohistological staining and immunoblotting revealed an increased expression of OPN in AF patients who present a higher degree of atrial fibrosis. Furthermore, in vitro studies in cultured human atrial fibroblasts (hAFs) demonstrated that OPN promoted the proliferation of fibroblasts and increased production of collagen I and fibronectin. Mechanistically, the profibrotic effects of OPN on atrial fibroblasts were determined via activating Akt/GSK-3β/β-catenin signaling and suppressing autophagy.This study uncovered a previously unrecognized profibrotic role of OPN in atrial fibrosis, which was achieved through activation of Akt/GSK-3β/β-catenin signaling pathway and suppression of autophagy, implying a promising therapeutic target in atrial fibrosis and AF.
    Keywords atrial fibrillation ; autophagy ; beta catenin ; catheters ; cell proliferation ; collagen ; enzyme-linked immunosorbent assay ; fibroblasts ; fibronectins ; fibrosis ; humans ; immunoblotting ; in vitro studies ; kidneys ; liver ; lungs ; messenger RNA ; osteopontin ; patients ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; signal transduction ; staining ; therapeutics
    Language English
    Dates of publication 2020-0315
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2020.117328
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Endowing Polyetheretherketone with Anti-Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection.

    Bai, Xinxin / Zhang, Xintian / Xiao, Jiecheng / Lin, Xingyu / Lin, Rongjie / Zhang, Rui / Deng, Xiaoqin / Zhang, Menghan / Wei, Wenqin / Lan, Bin / Weng, Shaohuang / Chen, Min

    Advanced healthcare materials

    2023  Volume 13, Issue 7, Page(s) e2302873

    Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infection and compromised immunity are the severe complications associated with implantation surgery in diabetes mellitus. Enhancing the antibacterial and immunomodulatory properties of implants ... ...

    Abstract Methicillin-resistant Staphylococcus aureus (MRSA) infection and compromised immunity are the severe complications associated with implantation surgery in diabetes mellitus. Enhancing the antibacterial and immunomodulatory properties of implants represents an effective approach to improve the osseointegration of implant in diabetes mellitus. Herein, guanidination carbon dots (GCDs) with antibacterial and immunoregulatory functions are synthesized. The GCDs demonstrate killing effect on MRSA without detectable induced resistance. Additionally, they promote the polarization of macrophages from the M1 to M2 subtype, with the inhibiting pro-inflammatory cytokines and promoting anti-inflammatory factors. Correspondingly, GCDs are immobilized onto sulfonated polyether ether ketone (SP@GCDs) using a polyvinyl butyraldehyde (PVB) coating layer through soaking-drying technique. SP@GCDs maintain stable antibacterial efficacy against MRSA for six consecutive days and retain the immunomodulatory function, while also possessing the long-term storage stability and biocompatibility of more than 6 months. Moreover, SP@GCDs significantly promote the proliferation and mineralization of osteoblasts. SP@GCDs facilitate osteogenesis through immunoregulatory. Additionally, SP@GCDs exert stable antibacterial and immune regulatory functions in implantation site of a diabetes rat, effectively promoting implant osseointegration regardless of the MRSA infection. These findings provide valuable insights into implant modification through designing nanomaterials with multifunction for enhancing osseointegration of diabetes mellitus, suggesting the promising clinical application prospects.
    MeSH term(s) Rats ; Animals ; Methicillin-Resistant Staphylococcus aureus ; Osseointegration ; Carbon ; Polyethylene Glycols/pharmacology ; Anti-Infective Agents/pharmacology ; Ketones/pharmacology ; Anti-Bacterial Agents/pharmacology ; Osteogenesis ; Diabetes Mellitus ; Surface Properties ; Benzophenones ; Polymers
    Chemical Substances polyetheretherketone (31694-16-3) ; Carbon (7440-44-0) ; Polyethylene Glycols (3WJQ0SDW1A) ; Anti-Infective Agents ; Ketones ; Anti-Bacterial Agents ; Benzophenones ; Polymers
    Language English
    Publishing date 2023-12-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202302873
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Extra pulmonary vein driver mapping and ablation in paroxysmal atrial fibrillation by electrogram dispersion analysis.

    Qin, Mu / Lin, Rong-Jie / Wu, Shao-Hui / Liu, Xu

    Journal of cardiovascular electrophysiology

    2018  Volume 30, Issue 2, Page(s) 164–170

    Abstract: Background: The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone.: Methods and results: A ... ...

    Abstract Background: The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone.
    Methods and results: A total of 98 patients with paroxysmal AF were enrolled in this study and were divided into two groups, with one group undergoing PVI (n = 49) and the other group undergoing PVI + driver ablation (n = 49). The driver regions were defined as clusters of bipolar electrograms that displayed spatial dispersion spread over mean AF cycle length at a minimum of three adjacent bipolars of a PentaRay catheter. During the procedure, the most prominent driver regions before PVI were the roof (n = 27; 55.1%), PV antrum (n = 23; 46.9%), and the inferoposterior wall (n = 11; 22.4%). PVI can eliminate all drivers at PV antrum, but only terminate 30.4% of AF in the driver group. The AF termination rate in the driver ablation group was significantly higher than that in conventional ablation (93.9% vs 40.6%; P < 0.001). The rate of freedom from atrial tachyarrhythmia episodes by a single procedure at 6 months was significantly higher in the driver group than in the conventional group (91.6% vs 72.4%; P = 0.02).
    Conclusion: The present method is effective for AF driver identification. It guided ablation adjunctive to PVI increasing the rate of AF termination and improving the outcomes in patients with paroxysmal AF.
    MeSH term(s) Action Potentials ; Aged ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/physiopathology ; Atrial Fibrillation/surgery ; Catheter Ablation/adverse effects ; Catheter Ablation/methods ; Electrophysiologic Techniques, Cardiac ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Progression-Free Survival ; Prospective Studies ; Pulmonary Veins/physiopathology ; Pulmonary Veins/surgery ; Recurrence ; Signal Processing, Computer-Assisted ; Time Factors
    Language English
    Publishing date 2018-11-21
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1025989-2
    ISSN 1540-8167 ; 1045-3873
    ISSN (online) 1540-8167
    ISSN 1045-3873
    DOI 10.1111/jce.13784
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Machine learning links different gene patterns of viral infection to immunosuppression and immune-related biomarkers in severe burns.

    Wang, Peng / Zhang, Zexin / Lin, Rongjie / Lin, Jiali / Liu, Jiaming / Zhou, Xiaoqian / Jiang, Liyuan / Wang, Yu / Deng, Xudong / Lai, Haijing / Xiao, Hou'an

    Frontiers in immunology

    2022  Volume 13, Page(s) 1054407

    Abstract: Introduction: Viral infection, typically disregarded, has a significant role in burns. However, there is still a lack of biomarkers and immunotherapy targets related to viral infections in burns.: Methods: Virus-related genes (VRGs) that were ... ...

    Abstract Introduction: Viral infection, typically disregarded, has a significant role in burns. However, there is still a lack of biomarkers and immunotherapy targets related to viral infections in burns.
    Methods: Virus-related genes (VRGs) that were extracted from Gene Oncology (GO) database were included as hallmarks. Through unsupervised consensus clustering, we divided patients into two VRGs molecular patterns (VRGMPs). Weighted gene co-expression network analysis (WGCNA) was performed to study the relationship between burns and VRGs. Random forest (RF), least absolute shrinkage and selection operator (LASSO) regression, and logistic regression were used to select key genes, which were utilized to construct prognostic signatures by multivariate logistic regression. The risk score of the nomogram defined high- and low-risk groups. We compared immune cells, immune checkpoint-related genes, and prognosis between the two groups. Finally, we used network analysis and molecular docking to predict drugs targeting
    Results: We established two VRGMPs, which differed in monocytes, neutrophils, dendritic cells, and T cells. In WGCNA, genes were divided into 14 modules, and the black module was correlated with VRGMPs. A total of 65 genes were selected by WGCNA, STRING, and differential expression analysis. The results of GO enrichment analysis were enriched in Th1 and Th2 cell differentiation, B cell receptor signaling pathway, alpha-beta T cell activation, and alpha-beta T cell differentiation. Then the 2-gene signature was constructed by RF, LASSO, and LOGISTIC regression. The signature was an independent prognostic factor and performed well in ROC, calibration, and decision curves. Further, the expression of immune cells and checkpoint genes differed between high- and low-risk groups.
    Discussion: This is the first VRG-based signature (including 2 key genes validated by qPCR) for predicting survival, and it could provide vital guidance to achieve optimized immunotherapy for immunosuppression in burns.
    MeSH term(s) Humans ; Molecular Docking Simulation ; Matrix Attachment Region Binding Proteins ; Immunosuppression Therapy ; Virus Diseases ; Machine Learning ; Biomarkers ; Burns/genetics
    Chemical Substances Matrix Attachment Region Binding Proteins ; Biomarkers ; SATB1 protein, human
    Language English
    Publishing date 2022-11-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1054407
    Database MEDical Literature Analysis and Retrieval System OnLINE

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