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Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 (AIM2), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.

BackgroundProstate cancer is the second most common cancer with a high risk of biochemical recurrence (BCR) among men. Recently, 5-methylcytosine (m5C) modification has attracted more attention as a new layer of RNA post-transcriptional regulation. Hence, we aimed at investigating the potential roles of m5C modification regulators in the BCR of prostate adenocarcinoma (PRAD).MethodsCNV data, mutation annotation data, mRNA expression profiles, and clinical data were downloaded from TCGA and GEO databases. Kaplan-Meier curves analysis, log-rank test, univariate and multivariate Cox regression, and time-dependent ROC curves analysis were performed to evaluate the prognostic factors. Principal components analysis (PCA) was applied to validate the distinction between subgroups. Gene set variation analysis (GSVA) was used to investigate the underlying pathways associated with m5C modification patterns. Single sample gene set enrichment analysis (ssGSEA) was utilized to assess the infiltration of distinct immune cells. Tumor Immune Dysfunction and Exclusion (TIDE) prediction was carried out to assess the potential response to immune checkpoint blockade (ICB) therapy. The m5C modification signature was constructed via LASSO Cox’s proportional hazards regression method.ResultsAfter comprehensively analyzing various types of data from TCGA dataset, and exploring the differential expression and prognostic value of each m5C regulator, we identified m5C modification patterns based on 17 m5C regulators. Two patterns presented a significant difference in the risk of BCR, the tumor microenvironment (TME), and immunotherapy response in PRAD. We found that TET2, which was highly expressed in adjacent normal tissues compared to tumor tissues, was closely associated with many infiltrating immune cells. The m5C modification signature was constructed for the clinical application. Risk score calculated by m5C signature was associated with T stage, N stage, Gleason score, and the possibility of BCR (HR, 4.197; 95% CI, 3.016-5.842; p < 0.001). A higher risk score also represented the possibility of immunotherapy response. Finally, the potential roles of m5C modification signature were validated in the testing dataset.ConclusionsOur study revealed the potential roles of m5C modification in the PRAD BCR and TME diversity, which may provide new insight into the field of prostate cancer in future research.

Glioma is the most common malignant tumor of the central nervous system. Tumor purity is a source of important prognostic factor for glioma patients, showing the key roles of the microenvironment in glioma prognosis. In this study, we systematically screened functional characterization related to the tumor immune microenvironment and constructed a risk model named Glioma MicroEnvironment Functional Signature (GMEFS) based on eight cohorts. The prognostic value of the GMEFS model was also verified in another two glioma cohorts, glioblastoma (GBM) and low-grade glioma (LGG) cohorts, from The Cancer Genome Atlas (TCGA). Nomograms were established in the training and testing cohorts to validate the clinical use of this model. Furthermore, the relationships between the risk score, intrinsic molecular subtypes, tumor purity, and tumor-infiltrating immune cell abundance were also evaluated. Meanwhile, the performance of the GMEFS model in glioma formation and glioma recurrence was systematically analyzed based on 16 glioma cohorts from the Gene Expression Omnibus (GEO) database. Based on multiple-cohort integrated analysis, risk subpathway signatures were identified, and a drug–subpathway association network was further constructed to explore candidate therapy target regions. Three subpathways derived from Focal adhesion (path: 04510) were identified and contained known targets including platelet derived growth factor receptor alpha (PDGFRA), epidermal growth factor receptor (EGFR), and erb-b2 receptor tyrosine kinase 2 (ERBB2). In conclusion, the novel functional signatures identified in this study could serve as a robust prognostic biomarker, and this study provided a framework to identify candidate therapeutic target regions, which further guide glioma patients’ clinical decision.

Natural killer (NK) cells are a type of innate lymphoid cell that are involved in the progression of acute myocardial infarction and ischemic stroke. Although multiple forms of programmed cell death are known to play important roles in these diseases, the correlation between NK cells and apoptosis-related genes during acute myocardial infarction and ischemic stroke remains unclear. In this study, we explored the distinct patterns of NK cell infiltration and apoptosis during the pathological progression of acute myocardial infarction and ischemic stroke using mRNA expression microarrays from the Gene Expression Omnibus database. Since the abundance of NK cells correlated positively with apoptosis in both diseases, we further examined the correlation between NK cell abundance and the expression of apoptosis-related genes. Interestingly, APAF1 and IRAK3 expression correlated negatively with NK cell abundance in both acute myocardial infarction and ischemic stroke, whereas ATM, CAPN1, IL1B, IL1R1, PRKACA, PRKACB, and TNFRSF1A correlated negatively with NK cell abundance in acute myocardial infarction. Together, these findings suggest that these apoptosis-related genes may play important roles in the mechanisms underlying the patterns of NK cell abundance and apoptosis in acute myocardial infarction and ischemic stroke. Our study, therefore, provides novel insights for the further elucidation of the pathogenic mechanism of ischemic injury in both the heart and the brain, as well as potential useful therapeutic targets.