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The ARF gene family is crucial for regulating plant growth, development, and responses to various signaling pathways. In this study, 26 quinoa ARF genes (CqARF01–CqARF26) were identified, with encoded proteins varying in length from 553 to 1092 amino acids, molecular weights from 60.66 to 111.71 kDa, and isoelectric points from 5.15 to 8.21. The proteins were found in either the nucleus (13 CqARFs) or cytoplasm (11 CqARFs). Phylogenetic analysis classified ARF proteins into five groups. All CqARFs contained seven conserved motifs (Motif1, Motif2, Motif4, Motif6, Motif8, Motif9, and Motif10), indicating conserved positions and functional similarities. Gene structure analysis showed that most CqARF genes had UTR regions at both ends, with similar structures within subgroups. Conserved sequence analysis revealed that motif composition within subgroups was relatively conserved. The presence of four classes of cis-regulatory elements in quinoa ARF genes suggests involvement in light, hormone, tissue-specific expression, and other responses. Expression analysis indicated that the most genes (CqARF05, CqARF07, CqARF15 and CqARF24) were highly expressed under drought and salt stress treatment. Overexpression of CqARF05 gene in Arabidopsis enhanced drought and salt resistance in transgenic lines. These findings provide valuable insights into the role of the ARF gene family. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction serves as one of the etiological factors for ischemic heart disease and represents a novel therapeutic direction for coronary artery diseases; however, the research on its pathogenesis remains inconsistent. This study aims to explore the single-cell gene expression profiles in rats with coronary microvascular dysfunction using single-cell RNA sequencing, with a particular focus on the in-depth analysis of endothelial cell gene expression characteristics. By establishing a rat model of coronary microvascular dysfunction, we collected cardiac apical tissue to prepare single-cell suspensions and further analyzed them using bioinformatics methods. From a total of 55,419 cells, we identified 28 distinct cell clusters, with endothelial cells and fibroblasts being the predominant cell types. Compared to the NC group, the proportion of endothelial cells in the CMD group was significantly reduced, while the number of fibroblasts was significantly increased. Through further analysis of the endothelial cells, we classified them into normal phenotype endothelial cells, mesenchymal phenotype endothelial cells, proliferative phenotype endothelial cells, and lymphatic endothelial cells, with mesenchymal and proliferative endothelial cells originating from normal phenotype endothelial cells. Additionally, the CMD group exhibited an increase in immune cells, enhanced inflammatory response, and increased oxidative stress. These findings may provide novel potential therapeutic targets for the treatment of Coronary microvascular dysfunction. [ABSTRACT FROM AUTHOR]

RPS6KA1 express disorder is associated with many cancers, but the role in head and neck squamous cell carcinoma (HNSCC) and the specific mechanism is still unclear. We used bioinformatics analysis to explore the role of Ribosomal Protein S6 Kinase A1(RPS6KA1) in HNSCC which were predicted to regulate certain pathway and immune microenvironment to increase the risk in HNSCC. Multiple bioinformatics tools based on the EBI, GEO, TCGA databases and clinical samples were used to analyze the expression of RPS6K1 in HNSCC. Western blot (WB) and PCR results confirmed the upregulation of RPS6KA1 in HNSCC tissues. Flow cytometry was used to validate the relationship between RPS6KA1 and immune cell infiltration in the tumor microenvironment. The correlation of RPS6KA1 with the immune environment was further analyzed, and flow cytometry validation was performed in HNSCC samples. Then, Gene Ontology(GO) and Gene Set Enrichment Analysis(GSEA) analysis were used to explore the pathway which could be regulated by RPS6KA1 in HNSCC. And drug sensitivity analysis was used to the access the relationships between RPS6KA1 and drugs therapeutic effects. EBI, TCGA and GEO databases were used to reveal that RPS6KA1 expression was significantly increased in HNSCC, especially in III + IV HNSCC. And it was related to many types of immune cells and immune adjustment factors and positively correlated with tumor immune score and B cells, but had no significant correlation with CD4+ and CD8+ T cells. Drug sensitivity analysis revealed that RPS6KA1 has certain predictive value. In this research, we indicated that RPS6KA1 is overexpressed and may serve as a potential diagnostic and therapeutic biomarker in HNSCC. [ABSTRACT FROM AUTHOR]

Purpose: Regenerating islet-derived protein 4 (REG4) is a secretory protein that belongs to the C-type lectin superfamily. This study aims to explore the diagnostic value of REG4 as a potential biomarker for metabolic syndrome by analyzing the correlation between serum REG4 levels and metabolic syndrome. Methods: Serum REG4 levels were measured using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analysis was conducted to investigate REG4-related genes and metabolic signaling pathways. Results: Serum REG4 levels were significantly elevated in MetS patients compared to healthy controls (439.7 vs. 422.6 ng/L, p < 0.01). In addition, circulating REG4 levels showed a positive correlation with AUGg, HbA1c, VAI, BMI, WHR, TG, TC, LDL-C, while being inversely correlated with HDL-C in the study population. Serum REG4 levels were positively correlated with MetS score. Multiple linear regression analysis identified HOMA-IR and LDL-C as independent factors affecting serum REG4 concentration. Interventional studies have shown that OGTT can significantly increase serum REG4 levels in healthy individuals, but significantly reduce REG4 levels in MetS patients. Bioinformatics analysis suggested that REG4 is linked to several metabolism-related genes and is enriched in various metabolism-related signaling pathways. Conclusion: REG4 may serve as a valuable biomarker and potential treatment target for insulin resistance (IR) and MetS. Clinical trial registration number: ChiCTR2000032878 [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PAAD) is one of the malignant tumors with poor prognosis. This study aims to inquiry the effects of Chromobox homologue 3 (CBX3) on PAAD progression. Pan-cancer analysis of CBX3 and its correlation with PAAD progression were investigated by informatics analysis. The role of CBX3 in PAAD was explored in vitro and in vivo. Cell viability, proliferation, migration and invasion were inspected by CCK-8 assay, EdU staining, scratch test and transwell assay, respectively. The morphology of tumors was observed by hematoxylin–eosin staining. Immunohistochemistry (Ki67) was performed to inspect the proliferation of tumor tissue. The protein levels were measured by western blot. Moreover, the downstream genes of CBX3 were screened, and the effects of target gene on PAAD was investigated in vitro. CBX3 was overexpressed in multi cancers, and high CBX3 expression indicated poor prognosis in PAAD. Through the in vitro assays, knockdown of CBX3 suppressed the viability, migration and invasion of PAAD cells, and restrained tumor growth in vivo. Subsequently, kinesin family member 20A (KIF20A) was screened as the downstream gene of CBX3, which was up-regulated in PAAD and related to low overall survival. Mechanistically, we discovered that CBX3 could regulate KIF20A expression. Knockdown of CBX3 promoted the oncogenic effects of KIF20A silencing on PAAD cells, and attenuated the pro-oncogenic effects of KIF20A overexpression on PPAD. Collectively, silencing CBX3 suppressed PAAD progression through regulating KIF20A expression, providing an underlying target for PAAD treatment. [ABSTRACT FROM AUTHOR]

Background: The family of SQUAMOSA promoter binding protein-like (SPL) transcription factors is essential for regulating plant growth and development. While this SPL gene functional research has been limited in Rhododendron molle (R. molle). Objective: To preliminarily explore the regulatory mechanism of the SPL gene in flower bud development of R. molle. Methods: In this study, for R. molle, the flower bud differentiation period was determined by observing the morphological anatomy of the flower bud. The SPL gene family members were identified based on the R. molle genome, Additionally, the expressions of RmSPL genes at five flower bud differentiation stages were analyzed via Quantitative reverse transcription PCR (RT–qPCR). Results: We first characterized 20 SPL family members in the reference genome of R. molle. The phylogenetic analysis of plant SPL proteins separated them into eight subfamilies (G1–G8) according to conserved gene structures and protein motifs. Cis-elements of promoter region analysis showed that RmSPL genes were regulated by light, phytohormones, stress response, and plant growth and development and may play a critical role in the photoresponse, abasic acid, anaerobic induction, and meristematic expression. Gene expression analysis showed that 18 RmSPL genes were differentially expressed in different developing flower buds. In particular, RmSPL1/7/8/12/13 exhibited significantly different expressions, suggesting that they were likely essential genes for regulating the differentiation of flower buds. Conclusion: In conclusion, our analysis of RmSPL genes provides a theoretical basis and reference for future functional analysis of RmSPL genes in the flower bud differentiation of R. molle. [ABSTRACT FROM AUTHOR]

PANoptosis is one of several modes of programmed cell death (PCD) and plays an important role in many inflammatory and immune diseases. The role of PANoptosis in inflammatory bowel disease (IBD) is currently unknown. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified, and pathway enrichment analyses were performed. LASSO regression model construction, a nomogram model, calibration curves, ROC and DCA curves were used to evaluate the predictive value of the model. Predicts transcription factors (TFs) and small-molecule drugs of DE-PRGs were analysed. Model genes and immuno-infiltration were analysed. The PANoptosis features of IBD include 12 genes: OGT, TLR2, GZMB, TLR4, PPIF, YBX3, CASP5, BCL2L1, CASP6, MEFV, GSDMB and BAX. The enrichment analysis suggested that these genes were related to TNF signalling, NF-κB, pyroptosis and necroptosis. Machine learning identified three model genes: OGT, GZMB and CASP5. The nomogram model, calibration curves, ROC and DCA curves have strong predictive value. Immuno-infiltration analysis revealed that immune cell infiltration was increased in patients with IBD, and the model genes were closely related to the infiltration of various immune cells. The TFs associated with DE-PRGs were RELA, NFKB1, HIF1A, TP53 and SP1. In addition, the Connectivity Map (CMap) database identified the top 10 small-molecule compounds, including buspirone, chloroquine, spectinomycin and chlortetracycline. This study indicate that DE-PRGs model genes have good predictive ability for IBD. Moreover, PANoptosis may mediate the process of IBD through TNF signalling, NF-κB, pyroptosis, necroptosis and immune mechanisms. These results present a new horizon for the research and treatment of IBD. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but the underlying molecular interactions remain unclear. This study aims to identify the molecular mechanisms of ERS in AS pathogenesis to inform innovative diagnostic approaches and therapeutic targets for managing AS. GSE28829 and GSE43292—human early and advanced carotid atherosclerotic tissue samples—were obtained from the Gene Expression Omnibus database. Endoplasmic reticulum stress-related genes (ERSRGs) were obtained from GeneCards. Differential gene expression and weighted gene co-expression network analyses were conducted to identify genes associated with atherosclerosis, and intersection with ER-related genes revealed three ERSRGs (i.e. CTSB, LYN, and CYBB) associated with advanced atherosclerotic plaque. These three ERSRGs exhibited associations with various immune cells. Additionally, the three ERSRGs were upregulated in human atherosclerotic tissues, mouse models of progressive atherosclerotic lesions, and in vitro macrophage models. In conclusion, this study identified CTSB, LYN, and CYBB as potentially critical ERSRGs associated with advanced atherosclerotic plaque, demonstrating their good diagnostic utility and offering novel insights into the potential pathobiology of AS progression, paving the way for exploring innovative therapeutic targets. [ABSTRACT FROM AUTHOR]

Estrogen sulfotransferase (SULT1E1), a member of the sulfotransferase family (SULTs), is the enzyme with the strongest affinity for estrogen. Despite significant associations between SULT1E1 and the progression and prognosis of a range of diseases, its functional role and potential mechanisms in lung adenocarcinoma (LUAD) remain unclear. The objective of this study was to examine the potential of SULT1E1 as a biomarker for LUAD. The molecular characteristics, disease relevance and expression levels of SULT1E1 in different cancers were analysed using public databases. GEPIA 2, Starbase and other databases were employed to analyse the expression levels of SULT1E1 in LUAD tissues and normal lung tissues, and to investigate the correlation with clinical stages. A prognostic analysis was conducted using the KM database and the tumour database. The SULT1E1 protein interaction network was constructed using the STRING database. The LUAD dataset from TCGA was employed for the purposes of performing functional enrichment and immune infiltration analyses. Subsequently, the expression levels of SULT1E1 in LUAD cell lines, human LUAD tissues and normal tissues were detected by Western blot and other methods. The expression of SULT1E1 was further detected by immunohistochemical staining, and the correlation between the expression level of SULT1E1 and the clinical characteristics and prognosis of LUAD patients was verified. The expression of SULT1E1 in cytoplasm and nucleus was detected by cellular immunofluorescence. Significant reductions in SULT1E1 expression were observed across various tissues and cell lines of LUAD, as supported by both bioinformatics and Western blotting analyses. Analysis of gene ontology suggested that SULT1E1 potentially exerts anticarcinogenic effects by modulating protein serine/threonine kinase activity and its associated pathway. Additionally, KEGG and GSEA analyses indicated SULT1E1's involvement in drug metabolism, choline metabolism in cancer, hormone synthesis, and other relevant pathways. Examination of immune infiltration demonstrated a strong correlation between SULT1E1 expression and the presence of immune cells such as TAM and Treg. Furthermore, SULT1E1 expression levels in LUAD were found to correlate with TNM stage, histological stage, platelet count to lymphocyte count ratio (PLR), neutrophil count to lymphocyte count ratio (NLR), and systemic immune-inflammation index (SII). Low SULT1E1 expression levels were significantly associated with shorter overall survival (OS) in LUAD patients. The suppression of lung adenocarcinoma (LUAD) by SULT1E1 makes it a potential biomarker for diagnosing and predicting the prognosis of LUAD. [ABSTRACT FROM AUTHOR]

Purpose: Oocyte aging is a significant factor in the negative reproductive outcomes of older women. However, the pathogenesis of oocyte aging remains unclear. This study aimed to identify the hub genes involved in oocyte aging via bioinformatics methods. Methods: The oocyte aging datasets GSE155179 and GSE158802 were obtained from the GEO database and analyzed as the training set. The GSE164371 dataset was then defined as the validation set. Differentially expressed genes were analyzed via the limma package and weighted gene coexpression network analysis, and intersected with cellular senescence-associated genes from the Cell Senescence database. The hub genes were identified via three machine learning algorithms, namely, support vector machine recursive feature elimination, random forest, and least absolute shrinkage and selection operator logistic, which were also confirmed via the validation set. Finally, a microRNA–mRNA‒transcription factor regulatory network and single-gene gene set enrichment analysis were performed to clarify the pathogenesis of oocyte aging. Results: A competing endogenous RNA network of GSE155179 and GSE158802 with 124 mRNAs, 31 long noncoding RNAs, and 31 miRNAs was constructed. Two modules with 814 genes were considered the key modules of oocyte aging. PDIK1L, SIRT1, and MCU were subsequently identified as hub genes; on the basis of these hub genes, a regulatory network of oocyte aging with 8 miRNAs, 3 mRNAs, and 227 TFs was ultimately constructed. Conclusions: This study contributes to a deeper understanding of oocyte aging and may aid in the development of therapeutic approaches to improve reproductive outcomes in older women. [ABSTRACT FROM AUTHOR]

The immune system has emerged as a major factor in the pathogenesis of Alzheimer’s disease (AD). PANoptosis is a newly defined programmed cell death mechanism related to many inflammatory diseases. This study aimed to identify the differentially expressed (DE) PANoptosis-related genes with characteristics of immune dysregulation (PRGIDs) in AD using bioinformatics analysis of bulk RNA-seq and single-nuclei RNA sequencing (snRNA-seq) data. To improve the robustness of gene selection, we integrated 3 microarray and 6 snRNA-seq datasets from the Gene Expression Omnibus (GEO), which allowed us to not only examine overall gene expression patterns but also assess the cellular specificity of gene expression at the single-cell level. This approach helped to identify cell-type-specific gene alterations that may be masked in bulk RNA-seq analyses. Relevant PANoptosis, immune dysregulation, and AD-related genes were obtained from the Genecards database. The AlzData database was also used in this study. Expression validation, the least absolute shrinkage and selection operator (LASSO) regression model, and CytoHubba algorithms were applied for key DE-PRGIDs selection. LASSO, Logistic, and Cox regressions were used to construct prognostic models. The receiver operating characteristic (ROC) curve and correlation analyses were conducted on key DE-PRGIDs. The Seurat package in R software was employed for performing snRNA-seq data processing. Uniform manifold approximation and projection (UMAP) was utilized for cell type annotation and PRGID cell visualization. The violin plot was applied for displaying expression levels of PRGIDs. High-dimensional consensus weighted gene co-expression network analysis (hdWGCNA) was conducted on microglia to identify gene modules and hub genes. Venn diagram analysis identified 250 PRGIDs and 39 DE-PRGIDs. NFKBIA was identified as the key gene. Prognostic models based on the expression level of NFKBIA were obtained. ROC curve analysis revealed its area under the curve (AUC) value: 0.661 in training set and 0.836 in validation set. The heatmap displayed the result of correlation analysis. SnRNA-seq data analysis identified 7 cell types. The UMAP and violin plots revealed highly expressed PRGIDs in microglia with remarkable differences between healthy controls and AD. hdWGCNA identified PVT1 and APOE as hub genes associated with microglia. In conclusion, our findings provide evidence that PANoptosis may play a role in the immune dysregulation observed in AD. PVT1 has been implicated in AD pathogenesis, potentially exerting its effects through the miR-488-3p/FOXD3/SCN2A axis. [ABSTRACT FROM AUTHOR]

The widely used Radix Astragali (RA) has significant therapeutic effects on cognitive impairment (CI) caused by type 2 diabetes (T2DM). However, the effective active ingredients and the precise mechanism underly RA alleviation of T2DM-induced CI still require further study. In this study, we aim to elucidate whether and how jaranol, a key effective active ingredient in RA, influences CI in db/db mice. We used various online databases and Cytoscape to screen jaranol as the most active ingredient of RA in the treatment of T2DM-induced CI. The fear conditioning experiment, new object recognition (NOR) test, and Morris water maze (MWM) test were conducted to assess the improvement effect of jaranol on CI in diabetic mice. The protein-protein interaction (PPI) network, Cytoscape, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key genes. The levels of AKT and caspase-3 were determined by Western blotting. The number of surviving hippocampal neurons was verified through Nissl staining. AutoDock was utilized for predicting potential binding sites between jaranol and key genes.As a result, jaranol attenuated CI in db/db mice probably through activation of PI3K-AKT signaling pathway by inhibiting cell apoptosis in hippocampus. Furthermore, A329 near the active site of AKT1 had hydrogen bond with jaranol. In conclusion, we suggest that jaranol may have therapeutic applications in T2DM-induced CI by targeting the PI3K-AKT signaling pathway directly via key sites. Our study provides alternative drugs and potential therapeutic targets for the prevention and treatment of T2DM-induced CI. [ABSTRACT FROM AUTHOR]

Focal cortical dysplasia (FCD) represents a common developmental malformation associated with drug-resistant epilepsy (DRE) among children. However, the exact molecular mechanisms behind this condition are still unclear. In our study, FCD-associated microarray data from the Gene Expression Omnibus (GEO) database were analyzed. A comprehensive series of bioinformatics analyses were conducted, including screening for differentially expressed genes (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) analysis. Subsequently, a freezing lesion (FL) rat model was developed to validate expression levels of hub genes along with the molecular pathways behind FCD epileptogenicity. 320 DEGs were identified, and functional enrichment analysis revealed significant enrichment of these DEGs in “Neuroinflammatory response”, “Cytokine production involved in immune response”, and “Macrophage activation”. Ultimately, 5 potential hub genes (CYBB, ITGAM, FCG3A, LY86, and CD86) were pinpointed. Notably, 4 hub genes (CYBB, ITGAM, FCG3A, and CD86) were validated in in vivo experiments, suggesting possible associations with neuroinflammation triggered by microglia. This underscores the tight relationship between microglia-induced neuroinflammation and the pathological progression of epileptic seizures in FCD. ITGAM, FCG3A, CD86, CYBB, and LY86 may emerge as promising candidate biomarkers, influencing diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this study, we aimed to work through the key genes involved in the process of pyroptosis in Alzheimer's disease (AD) to identify potential biomarkers using bioinformatics technology and further explore the underlying molecular mechanisms. The transcriptome data of brain tissue in AD patients were screened from the GEO database, and pyroptosis-related genes were analyzed. The functions of differential genes were analyzed by enrichment analysis and protein–protein interaction. The diagnostic model was established using LASSO and logistic regression analysis, and the correlation of clinical data was analyzed. Based on single-cell analysis of brain tissues of patients with AD, immunofluorescence and western blotting were used to explore the key cells affected by the hub gene. After GSEA, qRT-PCR, western blotting, LDH, ROS, and JC-1 were used to investigate the potential mechanism of the hub gene on pyroptosis. A total of 15 pyroptosis differentially expressed genes were identified. A prediction model consisting of six genes was established by LASSO and logistic regression analysis, and the area under the curve was up to 0.81. As a hub gene, CHMP4B was negatively correlated with the severity of AD. CHMP4B expression was decreased in the hippocampal tissue of patients with AD and mice. Single-cell analysis showed that CHMP4B was downregulated in AD microglia. Overexpression of CHMP4B reduced the release of LDH and ROS and restored mitochondrial membrane potential, thereby alleviating the inflammatory response during microglial pyroptosis. In summary, CHMP4B as a hub gene provides a new strategy for the diagnosis and treatment of AD. [ABSTRACT FROM AUTHOR]

The N6-methyladenosine (m6A) methyltransferase METTL3 has been demonstrated to function in mediating m6A modification, but its role in ischemic stroke (IS) has not been fully elucidated. This study aimed to explore the downstream mechanism of METTL3-mediated m6A modification in IS. GSE16561 and GSE22255 were downloaded from the Gene Expression Omnibus database for analysis of differentially expressed genes (DEGs), and it was found that METTL3 mRNA was downregulated in IS. Then quantitative real-time polymerase chain reaction was used to verify the downregulation of METTL3 mRNA in the peripheral blood of IS patients and the cortexes of transient middle cerebral artery occlusion mice. By combining DEGs with the m6A-downregulated genes in GSE142386 which performed methylated RNA immunoprecipitation sequencing (MeRIP‐seq) on METTL3‐deficient and control endothelial cells, a total of 131 genes were identified as the METTL3-mediated m6A-modified genes in IS. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the genes were mainly involved in cytokine-cytokine receptor interaction, MAPK signaling pathway and NF-kappa B signaling pathway. CTSS and SBK1 were further screened as the key METTL3-mediated m6A-modified genes by random forest model and PCR validation. The ROC curve analysis showed that the combination with CTSS and SBK1 was of good diagnostic value for IS, with the AUC of 0.810, sensitivity of 0.780, and specificity of 0.773. Overall, we found that METTL3-mediated m6A modification may influence the occurrence and development of IS by participating in inflammation-related biological processes, and two key m6A-modified genes mediated by METTL3 (CTSS and SBK1) can be used as diagnostic biomarkers for IS. [ABSTRACT FROM AUTHOR]

In recent years, nonalcoholic fatty liver disease (NAFLD) has become a more serious public health issue worldwide. This study strived to investigate the molecular mechanism of pathogenesis of NAFLD and explore promising diagnostic and therapeutic targets for NAFLD. Raw data from GSE130970 were downloaded from the Gene Expression Omnibus database. We used the dataset to analyze the expression levels of cuproptosis-related genes in NAFLD patients and healthy controls to identify the differentially expressed cuproptosis-related genes (DECRGs). The relationship and potential mechanism between DECRGs and clinicopathological factors were examined by enrichment analysis and two consensus clustering methods. We screened key DECRGs based on Random Forest (RF), and then verified the key DECRGs in NAFLD patients, high-fat diet (HFD)–fed mice, and palmitic acid–induced AML12 cells. ROC analysis showed good diagnostic function of DECRGs in normal and NAFLD liver tissue. Two consensus clusters indicated the important role of cuproptosis in the development of NAFLD. We screened for key DECRGs (DLD, DLAT) based on RF and found a close relationship between the DECRGs and clinicopathological factors. We collected clinical blood samples to verify the differences in gene expression levels by qPCR. In addition, we further verified the expression levels of DLD and DLAT in HFD mice and AML12 cells, which showed the same results. This study provides a novel perspective on the pathogenesis of NAFLD. We identified two cuproptosis-related genes that are closely related to NAFLD. These genes may play a significant role in the molecular pathogenesis of NAFLD, which may be useful to make progress in the diagnosis and treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Molecules in immune cells plays a vital role in the pathogenesis of ischemic stroke (IS). The aim of this study is to profile the landscape of molecules on the basis of immune cells in IS peripheral blood and construct an immunoregulatory competing endogenous RNA (ceRNA) network. We collected and combined multiple public transcriptome datasets from the peripheral blood of IS patients and healthy controls. CIBERSORT deconvolution revealed that the proportions of CD8 and CD4 naive T cells, monocytes, and neutrophils changed significantly in the IS group. Intersecting the immune cell-related genes identified by weighted gene co-expression network analysis (WGCNA) and differential expression analysis, 38 overlapping candidate biomarkers were selected. Three machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest were applied, and 11 distinct immune cell-related genes were identified. We obtained the mRNA-miRNA and miRNA-lncRNA interactions from StarBase v3.0, and constructed a ceRNA network based on the differentially expressed mRNAs, miRNAs, and lncRNAs. The aberrant expression of HECW2-centered ceRNAs in the peripheral blood of in-house patients was validated using quantitative PCR. We also revealed that the expression of HECW2 was positively correlated with lncRNAs LINC02593 through miRNAs miR-130a-3p, miR-130b-3p and miR-148b-3p in cells. These results show that there are distinct immune features between IS patients and healthy controls. The ceRNA network may help elucidate the mechanism of immune cell-related genes in IS and may serve as a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of osteoarthritis (OA) on the development of breast cancer (BC), and reveal the potential mechanisms underlying the association between them. Methods: A two-step, multivariable Mendelian Randomization (MR) analysis was performed, using statistics from genome-wide association studies (GWAS), to determine the effect of OA on BC and explore the role of major depressive disorder (MDD) in mediating it. Furthermore, transcriptomic analysis based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to establish a prognostic model and explore the underlying mechanisms. Additionally, BC cells and nude mice were used to verify the role of RTN4 in BC. Results: The two-sample MR analysis implied a causal relationship between OA and BC at the genetic level, and the mediating MR analysis identified that MDD may play a potential role in mediating it, accounting for approximately 12.20%. Then, we constructed a prognostic model (OA-score) with six genes screened out from datasets and selected RTN4 as the representative gene for validation study. It was demonstrated that high OA-score was an independent risk factor for breast cancer, and patients with low OA-score were more likely to have better OS, higher infiltration level of DC and CD 4 + T cells, and higher expression of some immune checkpoints. Moreover, the knockdown of RTN4 inhibited breast cancer cell proliferation, migration and invasion. Conclusion: Our study identified the causal influence of OA on BC mediated by MDD at the genetic level. OA-Score may potentially serve as a new prognostic biomarker for OA related BC patients. [ABSTRACT FROM AUTHOR]

Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an idiopathic, relapsing inflammatory disorder of the colonic mucosa. Pyroptosis contributes significantly to UC. However, the molecular mechanisms of UC remain unexplained. Herein, using transcriptome data and animal experimental validation, we sought to explore pyroptosis-related molecular mechanisms, signature genes, and potential drugs in UC. Gene profiles (GSE48959, GSE59071, GSE53306, and GSE94648) were selected from the Gene Expression Omnibus (GEO) database, which contained samples derived from patients with active and inactive UC, as well as health controls. Gene Set Enrichment Analysis (GSEA), Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on microarrays to unravel the association between UC and pyroptosis. Then, differential expressed genes (DEGs) and pyroptosis-related DEGs were obtained by differential expression analyses and the public database. Subsequently, pyroptosis-related DEGs and their association with the immune infiltration landscape were analyzed using the CIBERSORT method. Besides, potential signature genes were selected by machine learning (ML) algorithms, and then validated by testing datasets which included samples of colonic mucosal tissue and peripheral blood. More importantly, the potential drug was screened based on this. And these signature genes and the drug effect were finally observed in the animal experiment. GSEA and KEGG enrichment analyses on key module genes derived from WGCNA revealed a close association between UC and pyroptosis. Then, a total of 20 pyroptosis-related DEGs of UC and 27 pyroptosis-related DEGs of active UC were screened. Next, 6 candidate genes (ZBP1, AIM2, IL1β, CASP1, TLR4, CASP11) in UC and 2 candidate genes (TLR4, CASP11) in active UC were respectively identified using the binary logistic regression (BLR), least absolute shrinkage and selection operator (LASSO), random forest (RF) analysis and artificial neural network (ANN), and these genes also showed high diagnostic specificity for UC in testing sets. Specially, TLR4 was elevated in UC and further elevated in active UC. The results of the drug screen revealed that six compounds (quercetin, cyclosporine, resveratrol, cisplatin, paclitaxel, rosiglitazone) could target TLR4, among which the effect of quercetin on intestinal pathology, pyroptosis and the expression of TLR4 in UC and active UC was further determined by the murine model. These findings demonstrated that pyroptosis may promote UC, and especially contributes to the activation of UC. Pyroptosis-related DEGs offer new ideas for the diagnosis of UC. Besides, quercetin was verified as an effective treatment for pyroptosis and intestinal inflammation. This study might enhance our comprehension on the pathogenic mechanism and diagnosis of UC and offer a treatment option for UC. [ABSTRACT FROM AUTHOR]

Immune infiltration plays a crucial role in intervertebral disc degeneration (IDD). In this study, we explored the immune microenvironment of IDD through single-cell bioinformatics analysis. Three single-cell datasets were integrated into this study. Nucleus pulposus cells (NPCs) were divided into subgroups based on characteristic genes, and the role of each subgroup in the IDD process was analyzed through pseudo-time trajectory analysis. The hub genes were obtained using hdWGCNA, further identified by bulk datasets and pseudo-time sequence. The expression of the hub genes defined the NPCs related to immune infiltration, and the interaction between these NPCs and immunocytes was explored. The NPCs were divided into four subgroups: reserve NPCs, HCL-NPCs, response NPCs, and support NPCs, which, respectively, dominate the four processes of IDD: non, mild, moderate, and severe degeneration. SPP1 and ICAM1 were identified as the nucleus pulposus immune infiltration hub genes. Macrophages and myelocytes played pro-inflammatory roles in the SPP1-ICAM both-up NPC group through the SPP1-CD44 pathway and ICAM1-ITGB2 ligand-receptor pathway, respectively. At the same time, both-up NPCs sought self-help inflammation remission from neutrophils through the ANXA1-FPR1 pathway. The systematic analysis of the differentiation and immune infiltration landscapes helps to understand IDD's overall development process. Our data suggest that SPP1 and ICAM1 may be new targets for the treatment of inflammatory infiltration in IDD. [ABSTRACT FROM AUTHOR]

Rationale: Traumatic brain injury (TBI) is a critical condition associated with cognitive impairments, including dementia. This study is aimed to construct a long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network based on bioinformatics analysis and explore molecular mechanisms underlying post-TBI dementia. Methods: GSE104687 and GSE205661 datasets were downloaded from Gene Expression Omnibus database. Molecular Signatures Database (MSigDB) was used to search oxidative stress-, metabolism- and immune-related genes as the target gene datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were carried out for functional annotation and enrichment analysis. A TBI mouse model was built to validate the expression of NF2, PLXNA2, NCBP2 and U2SURP in brain tissues. Results: A total of 7 differentially expressed lncRNAs (DElncRNAs) and 191 DEmRNAs were obtained. Subsequent to differential expression (DE) analysis, a lncRNA-miRNA-mRNA network was established. Notably, 13 key DEmRNAs were identified, potentially playing pivotal roles in the pathogenesis of TBI-induced dementia. By comparing the target gene datasets with 13 DEmRNAs, we identified 4 target genes that overlap with the 13 DEGmRNAs, namely NF2, PLXNA2, NCBP2 and U2SURP. Functional enrichment analysis highlighted the involvement of neuronal projections in the dementia-enriched cluster, while the protective cluster showed associations with protein synthesis and ubiquitination pathways. Importantly, we explored potential drug interventions based on interactions with the above 4 target genes. Additionally, drug interaction prediction showed that NF2 could interact with SELUMETINIB, EVEROLIMUS and TEMSIROLIMUS. Conclusion: Our study provides insights into the complex regulatory networks underlying post-TBI dementia and suggests a potential role for three classes of drugs in managing dementia symptoms in TBI-induced dementia. [ABSTRACT FROM AUTHOR]

Recent research has shown that Doublecortin-like kinase 1 (DCLK1) is overexpressed in different types of cancer. It has recently been described as a cancer stem cells (CSCs) marker, is associated with carcinogenesis, and positively correlates with infiltration of multiple immune cell types in some cancers. However, studies focused on assessing DCLK1 expression in HCC are limited, and the role of DCLK1 in HCC tumor immunity remains to be determined. In this study, we used a modified model of the resistant hepatocyte (MRHM) to evaluate DCLK1 expression in HCC. Furthermore, DCLK1 expression in HCC was analyzed using TIMER 2.0, UALCAN, GEPIA, GEO, and HPA web-based tools. Correlations between DCLK1 expression and clinicopathological factors in patients were analyzed using the UALCAN web-based tool. Finally, correlations between DCLK1 and immune infiltrates were investigated using the TIMER 2.0 and TISIDB web-based tools. The results showed that DCLK1 is significantly overexpressed during progression of the HCC carcinogenic process in the MRHM. DCLK1 is overexpressed in HCC according to multiple publics web-based tools, and its overexpression is associated with cancer stage. Furthermore, DCLK1 expression was correlated with infiltration levels of multiple immune cells, immunomodulatory factors, immunoinhibitors, MHC molecules, chemokines, receptors, and immune cell-specific markers. These results suggest that DCLK1 is a potential prognostic biomarker that determines cancer progression and correlates with immune cell infiltration in HCC. [ABSTRACT FROM AUTHOR]

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein–protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of cancer mortality in women and a major risk to world health. Therefore, effective strategies are required for prompt diagnosis and treatment. Nowadays, non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs), have assumed a significant role in the prognosis and diagnosis of diseases, including cancer. In the present study, surveying the bioinformatic tools, including the lncRNADisease v2.0, OncoDB, InteractiVenn, GEPIA, RAID, COXPRESdb, DAVID v6.8, GEO2R, and LncSEA, we proposed the Maternally Expressed Gene (MEG3) as a potential biomarker in BC. This lncRNA significantly downregulates in BC and is associated with tumor size, metastasis, and pathological stage. MEG3 expression is downregulated in several types of primary human cancers and tumor cell lines, which raises the possibility that it could act as a tumor suppressor. The results suggest that MEG3 may play a crucial role in fundamental pathways, including apoptosis, and interact with essential genes and proteins such as P53. It may also be associated with the prognosis, proliferation, migration, invasion, and metastasis of BC. [ABSTRACT FROM AUTHOR]

Autophagy has been implicated in the pathogenesis and progression of spinal cord injury (SCI); however, its specific mechanisms remain unclear. This study is aimed at identifying potential molecular biomarkers related to autophagy in SCI through bioinformatics analysis and exploring potential therapeutic targets. The mRNA expression profile dataset GSE151371 was obtained from the GEO database, and R software was used to screen for differentially expressed autophagy-related genes (DE-ARGs) in SCI. A total of 39 DE-ARGs were detected in this study. Enrichment analysis, protein–protein interaction (PPI) network, TF-mRNA-miRNA regulatory network analysis, and the DSigDB database were used to investigate the regulatory mechanisms between DE-ARGs and identify potential drugs for SCI. Enrichment analysis revealed associations with autophagy, apoptosis, and cell death. PPI analysis identified the highest-scoring module and selected 10 hub genes to construct the TF-mRNA-miRNA network, revealing regulatory mechanisms. Analysis of the DSigDB database indicated that 1,9-Pyrazoloanthrone may be a potential therapeutic drug. Machine learning algorithms identified 3 key genes as candidate biomarkers. Additionally, immune cell infiltration results revealed significant correlations between PINK1, NLRC4, VAMP3, and immune cell accumulation. Molecular docking simulations revealed that imatinib can exert relatively strong regulatory effects on the three key proteins. Finally, in vivo experimental data revealed that the overall biological process of autophagy was disrupted. In summary, this study successfully identified 39 DE-ARGs and discovered several promising biomarkers, significantly contributing to our understanding of the underlying mechanisms of autophagy in SCI. These findings offer valuable insights for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) with complex molecular carcinogenesis represents a kind of prevalent neoplasm occurring in the liver. The objective of this study is to illustrate the function of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and underlying action mechanisms in HCC progression. Methods: Comprehensive bioinformatics methods were conducted to screen differentially expressed genes (DEGs), cuproptosis-associated DEGs, and hub genes. The correlation between BIRC5 and immune cell infiltration, prognosis value was evaluated. The specific effects of BIRC5 silencing on HCC cells was validated by functional assays, and the impact on tumorigenicity and cuproptosis was also elucidated in vivo. Additionally, the effects of BIRC5 deficiency on PPAR pathway were determined using Oroxin A in vitro. Results: A total of 45 cuproptosis-associated DEGs and 9 hub genes were discovered through bioinformatics. Then 6 core genes were confirmed in Hep-3B and SK-Hep-1 cells with 4 genes upregulated and 2 genes downregulated. Therein, BIRC5 was positively correlated with the infiltration of CD8+ T cells, macrophages, and highly expressed BIRC5 exhibited poor prognosis of overall survival in HCC. Furthermore, BIRC5 deletion inhibited the PPARγ pathway, thereby restraining the malignant phenotypes of HCC cells and tumorigenesis in vivo. Additionally, silencing of BIRC5 contributed to the initiation of cuproptosis in HCC. Conclusions: BIRC5 silencing attenuated HCC through blocking PPARγ pathway and regulating cuproptosis, which may offer therapeutic implications against HCC. [ABSTRACT FROM AUTHOR]

Pollen coat proteins (PCPs) are cysteine-rich small-molecule proteins, which exhibit high levels of polymorphism and are expressed in gametocytes. Previous investigations have revealed that PCP genes are involved in pollen wall synthesis, pollen-stigma recognition, and pollen development and germination. However, gene expression and function of PCP family in pollen development is not well understood in Wucai (Brassica campestris L.). In this study, genome-wide identification and expression analysis of the BcPCP gene family members were conducted, including their physical and chemical properties, chromosome localization, phylogenetic relationships, gene structure, and tertiary structure. A total of 20 BcPCP genes were identified and classified into three subfamilies showing high homology to Arabidopsis thaliana. Expression pattern analysis indicated that the BcPCP gene family exhibits higher expression levels in reproductive organs, suggesting their potential involvement in the reproductive development. Notably, BraA02g002400.3 C, potentially associated with male sterility, was identified through multiple transcriptomic and proteomic datasets. Subsequently, sequence analysis revealed its homology with the Arabidopsis GRP20 gene, and thus it was named BcGRP20. Functional analysis of this gene showed that overexpression of BcGRP20 gene in the Arabidopsis grp20 mutant could restore anther fertility. Overall, our findings indicate that BcGRP20 plays a critical role in pollen development and may be the causative gene for male sterility in Wucai. This study provides candidate genes for further functional identification of BcPCP genes in Wucai, which are crucial for anther development. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and aortic valve calcification, prevalent in the elderly, have unclear common mechanisms. This study aims to uncover them through bioinformatics analysis. Methods: Microarray data from GEO was analyzed for osteoporosis and aortic valve calcification. Differential expression analysis identified co-expressed genes. SVM-RFE and random forest selected key genes. GO and KEGG enrichment analyses were performed. Immunoinfiltration and GSEA analyses were subsequently performed. NetworkAnalyst analyzed microRNAs/TFs. HERB predicted drugs, and molecular docking assessed targeting potential. Results: Thirteen genes linked to osteoporosis and aortic valve calcification were identified. TNFSF11, KYNU, and HLA-DMB emerged as key genes. miRNAs, TFs, and drug predictions offered therapeutic insights. Molecular docking suggested 17-beta-estradiol and vitamin D3 as potential treatments. Conclusion: The study clarifies shared mechanisms of osteoporosis and aortic valve calcification, identifies biomarkers, and highlights TNFSF11, KYNU, and HLA-DMB. It also suggests 17-beta-estradiol and vitamin D3 as potential effective treatments. [ABSTRACT FROM AUTHOR]

This study explored the comorbid mechanisms between Crohn's disease (CD) and chronic obstructive pulmonary disease (COPD) using bioinformatics analysis. From the Gene Expression Omnibus (GEO) microarray dataset, 349 common differentially expressed genes (coDEGs) were identified, and 8 shared hub genes were found: CCL2, CXCL1, TLR2, ICAM1, PTPRC, ITGAX, PTGS2, and MMP9, which were vital for immune function and regulation of inflammatory responses. In addition, the study also analyzed the association between coDEGs and immune cell infiltration using the single-sample gene set enrichment algorithm (ssGSEA). Potential drugs related to these genes were identified using the connectivity map (CMap). These findings provided new perspectives for understanding the interaction between CD and COPD. [ABSTRACT FROM AUTHOR]

Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae, Apis mellifera, Bos taurus, Drosophila melanogaster, Danio rerio, Fugu rubripes, Gallus gallus, Homo sapiens, Monodelphis domestica, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Tetraodon nigroviridis, Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher (p < 0.01) than that in the ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus. The study also involved predicting miR-375 target genes. GO and KEGG enrichment analyses of these predicted target genes revealed that miR-375 is involved in 182 biological processes, affects 186 cellular components, and participates in 184 molecular functions. In terms of pathway enrichment, miR-375 was linked to nine pathways, including the Hippo, Wnt, and mTOR signaling pathways. This study has validated the interaction between miR-375 and its target gene FZD4, which can be recognized and bound to produce effects. These findings lead to the inference that miR-375 may play a crucial regulatory role in sheep reproduction through the Hippo pathway and Wnt pathway, laying a foundation for further exploration of miR-375's role in this domain. [ABSTRACT FROM AUTHOR]

Background: Diabetic Kidney Disease (DKD) is a complex disease associated with circadian rhythm and biological clock regulation disorders. Melatonin (MT) is considered a hormone with renal protective effects, but its mechanism of action in DKD is unclear. Methods: We used the GSE151325 dataset from the GEO database for differential gene analysis and further explored related genes and pathways through GO and KEGG analysis and PPI network analysis. Additionally, this study used a type 2 diabetes db/db mouse model and investigated the role of melatonin in DKD and its relationship with clock genes through immunohistochemistry, Western blot, real-time PCR, ELISA, chromatin immunoprecipitation (ChIP), dual-luciferase reporter technology, and liposome transfection technology to study DEC1 siRNA. Results: Bioinformatics analysis revealed the central position of clock genes such as CLOCK, DEC1, Bhlhe41, CRY1, and RORB in DKD. Their interaction with key inflammatory regulators may reveal melatonin's potential mechanism in treating diabetic kidney disease. Further experimental results showed that melatonin significantly improved the renal pathological changes in db/db mice, reduced body weight and blood sugar, regulated clock genes in renal tissue, and downregulated the TLR2/MyD88/NF-κB signaling pathway. We found that the transcription factor DEC1 can bind to the TLR2 promoter and activate its transcription, while CLOCK's effect is unclear. Liposome transfection experiments further confirmed the effect of DEC1 on the TLR2/MyD88/NF-κB signaling pathway. Conclusion: Melatonin shows significant renal protective effects by regulating clock genes and downregulating the TLR2/MyD88/NF-κB signaling pathway. The transcription factor DEC1 may become a key regulatory factor for renal inflammation and fibrosis by activating TLR2 promoter transcription. These findings provide new perspectives and directions for the potential application of melatonin in DKD treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes. [ABSTRACT FROM AUTHOR]

This study is designed to investigate the molecular pathways involved in X-chromosome inactivation (XCI) using the ATRX and XIST genes. Two 46,XX human embryonic stem cells (hESCs), one 46,XX, and one 47,XXX human induced pluripotent stem cell (iPSCs) with random or skewed XCI status were collected. Whole-genome transcriptional sequencing was performed on undifferentiated and differentiated cells, and bioinformatic analysis was performed on the transcriptional data. Gene expression levels in all samples were clustered into a relatively concentrated region, indicating that the gene expression in the samples was generally relatively consistent. Gene co-expression network analysis showed that 27 genes were highly associated with ARTX, with functions in mitochondria-mediated apoptosis-related complexes, DNA remodeling, transcriptional regulation, and messenger RNA (mRNA) synthesis and cleavage. Functional annotation revealed that ATRX might play a role in regulating the expression of XIST through DEAD-box family genes (DDX17, DDX56, and DDX6) and SWI1/SNF1 family genes (SMARCAD1, SMARCA5, and SMARCA4). Differential analysis of long non-coding RNAs (lncRNAs) on chromosome X showed that 18 lncRNAs were significantly different, and correlation co-efficient analysis revealed that PHEX-AS1, IDS2, and LINC00893 were strongly positively correlated with XIST, whereas ASMTL-AS1, TMSB15B-AS1, and LINC00632 were strongly positively correlated with ATRX. In conclusion, ATRX regulates XIST expression through SMARCAD1, SMARCA5, SMARCA4, DDX17, DDX56, and DDX6. A positive correlation was observed between lncRNAs and ATRX/XIST, confirming that ATRX plays a role in the onset and development of XCI. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a serious acute lung injury, and can develop into pulmonary fibrosis (PLF). Circular RNAs (circRNAs) regulatory network in ARDS is important. The study explored the role of hsa_circ_0006892 in the occurrence of ARDS and the development of PLF. Methods: Hsa_circ_0006892 levels were verified in serum samples of 203 ARDS patients with or without PLF, and the diagnostic value was evaluated through ROC. Cox regression analysis was performed to identify PLF-related factors. The downstream target genes were predicted online. The function and pathway of key genes were annotated through GO and KEGG pathway analysis. Protein-protein interaction (PPI) analysis was performed for the examination of protein interactions. Results: qRT-PCR determined the downregulation of hsa_circ_0006892 in the serum of both ARDS and PLF patients. Hsa_circ_0006892 can differentiate ARDS from controls, and independently related to the development of PLF. Nine targeted related miRNAs were integrated with dysregulated miRNAs from GSE27430 dataset. Clinically, miR-486-3p was the only miRNA that was significantly different in both ARDS and PLF groups, and was determined to be the target of hsa_circ_0006892. 180 target genes of miR-486-3p were predicted, which were integrated with ARDS and PLF-related GSE84439 and GSE38958 datasets. Go and KEGG pathway analysis identified Ras signaling pathway as the most commonly enriched pathway in the overlapped genes. Conclusions: The present results identified the differentially expressed hsa_circ_0006892 in ARDS and PLF, and suggested a possible molecular mechanism of hsa_circ_0006892/miR-486-3p axis. [ABSTRACT FROM AUTHOR]

Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis. [ABSTRACT FROM AUTHOR]

As components of a family of proteins with peptidyl-prolyl isomerase activity family, FKBP (FK506-binding protein) and CYP (Cyclophilins) exert crucial roles in various physiological and biochemical processes such as cell signal transduction and stress resistance. The functions of the FKBP or CYP family have been extensively discussed in various organisms, while the comprehensive characterization of this family in Setaria italica remains unreported. In this study, a total of 22 SiFKBPs and 26 SiCYPs genes were identified in the genome of Setaria italica, with highly conserved functional domains observed within each member of these gene families. Phylogenetic analysis revealed that both FKBP and CYP proteins from Setaria italica and other plant species clustered into nine distinct groups. Furthermore, RT-qPCR results indicated that certain genes were induced specifically under salt stress while others were induced under heat stress, suggesting their involvement in stress response processes. The analysis of gene function revealed that SiFKBP16-3 exhibits some degree of functional conservation. [ABSTRACT FROM AUTHOR]

Copper-induced cell death is regulated through protein lipoylation, which is critical for gene expression and phenotypic regulation. Neverless, the role of Cuproptosis-related genes in breast cancer (BC) remains unknown. This study aimed to construct a prognostic signature based on the expression of Cuproptosis-related genes in order to guide the diagnosis and treatment for BC. Cuproptosis-related genes prognostic signature has ata of 1250 BC tissues and 583 normal breast tissues were obtained from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and GEO GSE65212. The prognostic signature was established and evaluated with nineteen Cuproptosis-related genes. A series of in silico analyses based on SLC31A1, included expression analysis, independent prognostic analysis, correlation analysis, immune-related analysis and survival analysis. Finally, a series of cell experiments (including quantitative real-time polymerase chain reaction and western blot), and mice experiments were applied to evaluate the impact of SLC31A1 on BC. Cuproptosis-related genes prognostic signature has good predictive promising for survival in BC patients. We discovered that SLC31A1SLC31A1 was overexpressed in BC and was its independent prognostic factor. High expression of the SLC31A1 was correlated with poor prognosis and immune infiltrating of BC. SLC31A1 expression is associated with immune, chemotherapeutic and targeted therapy outcomes in BC. The proliferation, migration, and invasiveness of Her2 + enriched BC cells were decreased by SLC31A1 knockdown, also resulting in a decrease in tumor volume in mouse model. SLC31A1 is a candidate biomarker or therapeutic target in precision oncology, with diagnostic and prognostic significance in BC. [ABSTRACT FROM AUTHOR]

Soft rot is one of the top ten most dangerous plant pathogens in agricultural production, storage, and transport, and the use of microorganisms and their metabolites to control soft rot is a current research hotspot. In this study, we identified the antimicrobial substance in the metabolite of Paenibacillus polymyxa KH-19, and determined that the antimicrobial substance of this strain was an active protein. The protein was completely precipitated at 40–60% ammonium sulphate saturation and showed good inhibitory effects against seven pathogenic bacteria including Pectobacterium carotovorum BC2 and seven pathogenic fungi including Pyricularia oryzae. The MIC of the protein was 51.563 µg/mL, temperature acid–base UV and light stability insensitive to protease, with high-temperature resistance. The antimicrobial protein was isolated and purified by DEAE-anion exchange column and Sephadex G-75 gel filtration chromatography, and the LC–MS/MS assay identified the protein as lysophosphatidyl esterase with a molecular weight of 25.255 kDa. The purified antimicrobial protein increased the inhibitory effect against P. carotovorum BC2, with the diameter of the circle of inhibition being 26.50 ± 0.915 mm. Bioinformatics analysis showed that the protein has the molecular formula of C1117H1732N316O338S5, encodes 224 amino acids, has an aliphatic index of 88.39, and belongs to the category of hydrophilic unstable proteins. The present study is the first report of an active protein with extreme thermoplastic and resistance to P. carotovorum BC2, which provides a reference for the preparation and application of the antimicrobial substances of P. polymyxa KH-19, as well as a theoretical basis for the study of the function of lysophosphodiesterase protein and its use as a microbial preparation. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram's area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD. [ABSTRACT FROM AUTHOR]

Previous studies have shown a relationship between SPECC1 and the prognosis of breast cancer, indicating a potential function for SPECC1 in the initiation and progression of cancer. However, the role played by SPECC1 in other tumors is not yet known. Therefore, we used bioinformatics techniques to conduct a thorough investigation into the possible mechanism of SPECC1 in pan-cancer, analyzing data reported in the literature as well as databases such as GTEx and CCLE, cBioportal, TCGA, and UCSC XENA. Comparing the results with matching normal tissues, the majority of cancers, including pancreatic adenocarcinoma (PAAD) and breast invasive carcinoma (BRCA), exhibited higher levels of SPECC1, while hepatocellular carcinoma (HCC) showed lower expression levels. SPECC1 was also found to be genetically mutated in endometrial cancer, sarcoma, and esophageal cancer. The prognosis of lung adenocarcinoma, kidney papillary cell carcinoma, and breast cancer is highly correlated with dysregulation of SPECC1 expression. This work helps guide clinical therapy by highlighting the sensitivity of tumor-treating medicines and the prognostic importance of SPECC1 in various malignancies. KEGG pathway enrichment analysis revealed focused adhesion, collagen-containing extracellular matrix (collagen), and the primary enrichment domains for SPECC1-related genes. These findings were obtained through gene annotation (GO) examination of SPECC1 expression. Primary mediators of the cytokine-cytokine receptor interaction include PICOC1-associated genes, cell-substrate junction genes, and extracellular matrix containing collagen. PICOC1-associated genes primarily mediate the PI3K-AKT signaling pathway. Drug sensitivity assay showed that SPECC1 high-expressing cell lines were more sensitive to docetaxel, doxorubicin, etc. In conclusion, the current study shows how SPECC1 is expressed in different cancers and how this expression relates to the prognosis of the tumor. It also revealed the mutations and copy number variations of SPECC1 in various tumors and its potential involvement in cellular pathway regulatory networks and cytological processes. This study examines the relationship between immune genes, cellular infiltration, and immunological scores in the tumor microenvironment, which explain the severity of the disease. This study looks at the response of SPEC1 expression to anticancer therapy. Explains the prognostic significance and drug response of SPECC-1. [ABSTRACT FROM AUTHOR]

The toll-like receptor (TLR) family is an important class of proteins involved in the immune response. However, little is known about the association between TLRs and Esophageal squamous cell cancer (ESCC). We explored differentially expressed genes (DEGs) between ESCC and esophagus tissues in TCGA and GTEx database. By taking the intersection with TLR gene set and using univariate Cox analysis and multivariate Cox regression analysis to discriminate the hub genes, we created a TLR-prognostic model. Our model separated patients with ESCC into high- and low-risk score (RS) groups. Prognostic analysis was performed with Kaplan–Meier curves. The two groups were also compared regarding tumor immune microenvironment and drug sensitivity. Six hub genes (including CD36, LGR4, MAP2K3, NINJ1, PIK3R1, and TRAF3) were screened to construct a TLR-prognostic model. High-RS group had a worse survival (p < 0.01), lower immune checkpoint expression (p < 0.05), immune cell abundance (p < 0.05) and decreased sensitivity to Epirubicin (p < 0.001), 5-fluorouracil (p < 0.0001), Sorafenib (p < 0.01) and Oxaliplatin (p < 0.05). We constructed a TLR-based model, which could be used to assess the prognosis of patients with ESCC, provide new insights into drug treatment for ESCC patients and investigate the TME and drug response. [ABSTRACT FROM AUTHOR]

Introduction: Rhoptries proteins (ROPs) are crucial throughout different stages of the Toxoplasma gondii (T. gondii) lifecycle, playing key roles in both the invasion of host cells and their subsequent survival. ROP34 is particularly noteworthy as it significantly influences host gene expression and aids in the transition from the tachyzoite to the bradyzoite form. Materials and methods: This research utilized various bioinformatics tools to assess physico-chemical properties, allergenic and antigenic characteristics, sites for post-translational modifications (PTMs) and protein's secondary and three-dimensional structures of the ROP34 protein. Furthermore, the study identified potential B-cell, MHC-binding, and cytotoxic T-lymphocyte (CTL) epitopes within the ROP34 sequence. Results: The ROP34 peptide comprised 553 amino acid residues, with a calculated average molecular weight (MW) of 61.60149 kDa, an aliphatic index of 73.98, and a GRAVY score of − 0.554. The antigenicity of the multi-epitope peptide was estimated to be 0.526563 and 0.6025 by the ANTIGENpro and VaxiJen servers, respectively, suggesting ROP34 as an immunogenic protein with no allergenic potential. Secondary structure analysis revealed a composition of 52.80% random coil, 36.17% alpha helix, and 11.03% extended strand. The Ramachandran plot for the refined model depicted that 97.46% of the residues were situated in the favored region. Conclusion: This in silico research serves as a foundation for designing effective immunization tactics to target toxoplasmosis. The present article lays the groundwork for future studies and offers perspectives for the advancement of an appropriate toxoplasmosis vaccine.Highlights: Toxoplasmosis represents a significant global concern, especially for pregnant individuals and those with weakened immune systems This article provided a comprehensive definition of the important aspects of the ROP34 protein using several bioinformatics tools. We present insightful bioinformatics insights regarding the ROP34 protein, demonstrating its potential as a future vaccine choice. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary intracranial malignancy with a very low survival rate. Exploring key molecular markers for GBM can help with early diagnosis, prognostic prediction, and recurrence monitoring. This study aims to explore novel biomarkers for GBM via bioinformatics analysis and experimental verification. Dataset GSE103229 was obtained from the GEO database to search differentially expressed lncRNA (DELs), mRNAs (DEMs), and miRNAs (DEMis). Hub genes were selected to establish competing endogenous RNA (ceRNA) networks. The GEPIA database was employed for the survival analysis and expression detection of hub genes. Hub gene expression in GBM tissue samples and cell lines was validated using RT-qPCR. Western blotting was employed for protein expression evaluation. SYT1 overexpression vector was transfected in GBM cells. CCK-8 assay and flow cytometry were performed to detect the malignant phenotypes of GBM cells. There were 901 upregulated and 1086 downregulated DEMs identified, which were prominently enriched in various malignancy-related functions and pathways. Twenty-two hub genes were selected from PPI networks. Survival analysis and experimental validation revealed that four hub genes were tightly associated with GBM prognosis and progression, including SYT1, GRIN2A, KCNA1, and SYNPR. The four genes were significantly downregulated in GBM tissues and cell lines. Overexpressing SYT1 alleviated the proliferation and promoted the apoptosis of GBM cells in vitro. We identify four genes that may be potential molecular markers of GBM, which may provide new ideas for improving early diagnosis and prediction of the disease. [ABSTRACT FROM AUTHOR]

The molecular mechanism of sterility in cattleyak is still unresolved. The related factors of infertility in cattleyak were studied by tissue section, SERPINA5 gene cloning and bioinformatics technology. Tissue sections of the epididymis showed poorly structured and disorganized epithelial cells in the corpus of the epididymis compared to the caput of the epididymis, while in the cauda part of the epididymis, the extra basal smooth muscle was thinner, the surface of the epithelial lumen was discontinuous and the epithelium was markedly degenerated. The results of gene cloning showed that the coding sequence (CDS) region of the SERPINA5 gene in cattleyak was 1215 bp in length, encoding a total of 404 amino acids, of which the isoleucine content was the highest, accounting for a total of 49 amino acids (12.1%). The results of real-time fluorescence quantitative PCR (qPCR) showed that the expression of the SERPINA5 gene in the epididymis caput in cattleyak was significantly higher than that in the corpus and cauda (P < 0.05), but there were no significant differences between the corpus and cauda. In the current study, histological and bioinformatics analysis, physicochemical properties, and the expression analysis of the SERPINA5 gene in different regions of the epididymis in cattleyak were carried out to explore the biological complications of cattleyak infertility. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a common chronic joint disease globally. Synovial inflammation plays a pivotal role in its pathogenesis, preceding cartilage damage. Identifying biomarkers in osteoarthritic synovial tissues holds promise for early diagnosis and targeted interventions. Gene expression profiles were obtained from the Gene Expression Omnibus database. Subsequent analyses included differential expression gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) on the combined datasets. We performed functional enrichment analysis on the overlapping genes between DEGs and module genes and constructed a protein–protein interaction network. Using Cytoscape software, we identified hub genes related to the disease and conducted gene set enrichment analysis on these hub genes. The CIBERSORT algorithm was employed to evaluate the correlation between hub genes and the abundance of immune cells within tissues. Finally, Mendelian randomization analysis was utilized to assess the potential of these hub genes as biomarkers. We identified 46 differentially expressed genes (DEGs), comprising 20 upregulated and 26 downregulated genes. Using WGCNA, we constructed a gene co-expression network and selected the most relevant modules, resulting in 24 intersecting genes with the DEGs. KEGG enrichment analysis of the intersecting genes identified the IL-17 signaling pathway, associated with inflammation, as the most significant pathway. Cytoscape software was utilized to rank the candidate genes, with JUN, ATF3, FOSB, NR4A2, and IL6 emerging as the top five based on the Degree algorithm. A nomogram model incorporating these five genes, supported by ROC curve analysis, validated their diagnostic efficacy. Immune infiltration and correlation analysis revealed that macrophages were significantly associated with JUN (p < 0.01), FOSB (p < 0.01), and NR4A2 (p < 0.05). Additionally, T follicular helper cells showed significant associations with ATF3 (p < 0.05), FOSB (p < 0.05), and JUN (p < 0.05). Mendelian randomization analysis provided strong evidence linking JUN (IVW: OR = 0.910, p = 0.005) and IL6 (IVW: OR = 1.024, p = 0.026) with KOA. Through the utilization of various bioinformatics analysis methods, we have pinpointed key hub genes relevant to knee osteoarthritis. These findings hold promise for advancing pre-symptomatic diagnostic strategies and enhancing our understanding of the biological underpinnings behind knee osteoarthritis susceptibility genes. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a significant disease that affects people's physical and mental health. Currently, the treatment outcomes still do not meet clinical needs, and the causes of the disease are still unclear, therefore further exploration is needed. Methods: We analyzed the exposure factors of lung cancer, including gut microbiota, serum metabolites, and cytokines, through Mendelian randomization studies and bioinformatics analysis. We identified common SNPs and performed gene annotation, leading to the discovery of the key gene SURF4, which may affect the onset of lung cancer. We validated the oncogenic function and mechanism of SURF4 through public data analysis using GO and KEGG, and constructed a ceRNA network, revealing the lung cancer oncogenic pathway involving lncRNA/pseudogene-microRNA-SURF4. Results: We first conducted a Mendelian randomization analysis on 418 gut microbiota, 1400 serum metabolites, and 41 cytokines in relation to lung cancer. We found that 16 gut microbiota, 29 serum metabolites, and 2 cytokines were closely associated with lung cancer. Further comparison of all differential SNPs revealed that rs550057 on chromosome 9 was a common SNP among these three exposure factors, indicating its crucial role in lung cancer formation. Through gene functional annotation using R language, we found that the expression of 15 genes, including SURF4, was influenced by rs550057. By querying these 15 genes from public databases for their differential expression and prognosis in lung cancer, we found significant differences in SURF4, MED22, and RPL7A. Furthermore, by querying the expression and correlation coefficients of upstream microRNAs of these three genes through the starBase website, we found that hsa-miR-193a-5p-SURF4 had the most significant effect on lung cancer. Through GO and KEGG analysis of SURF4-related genes, we identified the molecular pathways associated metabolic synthesis and microbial infection related to the promotion of lung cancer by SURF4. This validated the results of the previous Mendelian randomization study. Furthermore, we constructed a ceRNA network for SURF4 and identified two upstream differentially expressed pseudogenes and nine lncRNAs, confirming the functionality of the pseudogene/lncRNA-microRNA-SUFR4 pathway. Conclusions: In summary, we have elucidated the regulatory role of the pseudogene/lncRNA-microRNA-SUFR4 pathway in the progression of lung cancer, combining the research hotspots of gut microbiota-serum metabolites-cytokines. We have also confirmed the pathway and mechanism through SURF4 and its related genes promoting lung cancer formation. This may provide effective therapeutic methods for lung cancer and serve as a potential prognostic marker. [ABSTRACT FROM AUTHOR]

Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammation. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function and underlying mechanisms of FABP4 in the progression of ASH. We first obtained alcoholic hepatitis (AH) datasets from the National Center for Biotechnology Information–Gene Expression Omnibus database and conducted bioinformatics analysis to identify critical genes in the FABP family. We then established ASH models of the wild-type (WT) and Fabp4-deficient (Fabp4−/−) mice to investigate the role of FABP4 in ASH. Additionally, we performed transcriptional profiling of mouse liver tissue and analyzed the results using integrative bioinformatics. The FABP4-associated signaling pathway was further verified. FABP4 was upregulated in two AH datasets and was thus identified as a critical biomarker for AH. FABP4 expression was higher in the liver tissues of patients with alcoholic liver disease and ASH mice than in the corresponding control samples. Furthermore, the Fabp4−/− ASH mice showed reduced hepatic lipid deposition and inflammation compared with the WT ASH mice. Mechanistically, Fabp4 may be involved in regulating the p53 and sirtuin-1 signaling pathways, subsequently affecting lipid metabolism and macrophage polarization in the liver of ASH mice. Our results demonstrate that Fabp4 is involved in the progression of ASH and that Fabp4 deficiency may ameliorate ASH. Therefore, FABP4 may be a potential therapeutic target for ASH treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to utilize bioinformatics methods to systematically screen and identify susceptibility genes for cervical cancer, as well as to construct and validate an mitophagy-related genes (MRGs) diagnostic model. The objective is to increase the understanding of the disease’s pathogenesis and improve early diagnosis and treatment. Method: We initially collected a large amount of genomic data, including gene expression profile and single nucleotide polymorphism (SNP) data, from the control group and Cervical cancer (CC) patients. Through bioinformatics analysis, which employs methods such as differential gene expression analysis and pathway enrichment analysis, we identified a set of candidate susceptibility genes associated with cervical cancer. Results: MRGs were extracted from single-cell RNA sequencing data, and a network graph was constructed on the basis of intercellular interaction data. Furthermore, using machine learning algorithms, we constructed a clinical prognostic model and validated and optimized it via extensive clinical data. Through bioinformatics analysis, we successfully identified a group of genes whose expression significantly differed during the development of CC and revealed the biological pathways in which these genes are involved. Moreover, our constructed clinical prognostic model demonstrated excellent performance in the validation phase, accurately predicting the clinical prognosis of patients. Conclusion: This study delves into the susceptibility genes of cervical cancer through bioinformatics approaches and successfully builds a reliable clinical prognostic model. This study not only helps uncover potential pathogenic mechanisms of cervical cancer but also provides new directions for early diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

Cervical malignancy (CC) is the 2nd most prevalent malignancy among females, leading to cancer mortality. Primary detection of CC tumors results in an improved prognosis. CC is a malignant gynecological tumor, with few treatment options. New diagnostic and therapeutic agents are required to expand patient survival and quality of life. If CC tumors can be found at an early stage, the prognosis is much brighter. New diagnostic and therapeutic agents are needed to increase patient survival and quality of life. In this work, we performed whole-exome sequencing utilizing V5 (Illumina platform) 10 samples, 5 control and 5 CC tumour tissue, and we compared the results with transcriptome studies. KMT2C variations were shown to be among the most vicious in this analysis. From an Indian viewpoint, we found a plethora of SNVs and mutations, including those with known, unknown, and possible effects on health. Based on our findings, we know that the KMT2C gene is on chr. Seven and in exon 8, all three recognized variants are missense, synonymous, coding synonymous, non-coding variants, and GnomAD MAF (− 0.05). The variation at position (7:152265091, T > A, SNV 62478356) in KMT2C is unique, potent, and pathogenic. The missense coding transcript CIQTNF maps to chromosome 7 and displays T > C SNV. In addition, we performed single strand conformational polymorphism analysis on 64 samples and further confirmed them using Sanger sequencing to understand and verify the mutations. KMT2C shows a log FC value of − 1.16. Understanding emerging harmful mutations from an Indian viewpoint is facilitated by our bioinformatics-based, extensive correlation studies of WES analysis. Potentially harmful and new mutations were found in our preliminary analysis; among these ten top mutated genes, KMT2C and CIQTNF were altered in ten cases of CC with an Indian phenotype. [ABSTRACT FROM AUTHOR]