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Introduction: The rapid spread of plasmid-mediated tet(X4) conferring high tigecycline resistance poses a significant threat to public health. Escherichia coli as the most common pathogen which carries tet(X4) has been widely disseminated in China. Thus, comprehensive investigations are required to understand the mechanism of transmission of tet(X4)-positive E. coli. Methods: In this study, a total of 775 nonduplicate samples were collected in Guangdong, China from 2019 to 2020. We screened for tet(X4)-positive E. coli by PCR amplification and species identification. Furthermore, we analyzed the phylogenetics and genetic context of tet(X4)-positive E. coli through wholegenome sequencing and long-reads sequencing. Results: Overall, 146 (18.84%) tet(X4)-positive E. coli were isolated, comprising 2 isolates from humans and 144 isolates from pigs. The majority of tet(X4)-positive E. coli exhibited resistance to multiple antibiotics but all of them were susceptible to amikacin and colistin. Phylogenetic analysis showed that ST877, ST871, and ST195 emerged as the predominant sequence types in tet(X4)-positive E. coli. Further analysis revealed various genetic environments associated with the horizontal transfer of tet(X4). Notably, a 100-kbp large fragment insertion was discovered downstream of tet(X4), containing a replicon and a 40-kbp gene cluster for the bacterial type IV secretion system. Discussion: The high colonization rate of tet(X4)-positive E. coli in animals suggests that colonization as a key factor in its dissemination to humans. Diverse genetic context may contribute to the transfer of tet(X4). Our findings underline the urgent need for controlling the spread of plasmid-mediated tigecycline resistance. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) is characterized by bone mass decrease and bone tissue microarchitectural deterioration in bone tissue. This study identified potential biomarkers for early diagnosis of OP and elucidated the mechanism of OP. Methods: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) for the GSE56814 dataset. A gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify key modules associated with healthy and OP samples. Functional enrichment analysis was conducted using the R clusterProfiler package for modules to construct the transcriptional regulatory factor networks. We used the "ggpubr" package in R to screen for differentially expressed genes between the two samples. Gene set variation analysis (GSVA) was employed to further validate hub gene expression levels between normal and OP samples using RT-PCR and immunofluorescence to evaluate the potential biological changes in various samples. Results: There was a distinction between the normal and OP conditions based on the preserved significant module. A total of 100 genes with the highest MM scores were considered key genes. Functional enrichment analysis suggested that the top 10 biological processes, cellular component and molecular functions were enriched. The Toll-like receptor signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, osteoclast differentiation, JAK-STAT signaling pathway, and chemokine signaling pathway were identified by Kyoto Encyclopedia of Genes and Genomes pathway analysis. SIRT1 and ZNF350 were identified by Wilcoxon algorithm as hub differentially expressed transcriptional regulatory factors that promote OP progression by affecting oxidative phosphorylation, apoptosis, PI3K-Akt-mTOR signaling, and p53 pathway. According to RT-PCR and immunostaining results, SIRT1 and ZNF350 levels were significantly higher in OP samples than in normal samples. Conclusion: SIRT1 and ZNF350 are important transcriptional regulatory factors for the pathogenesis of OP and may be novel biomarkers for OP treatment. [ABSTRACT FROM AUTHOR]

Background: Globally, the most common form of arrhythmias is atrial fibrillation (AF), which causes severe morbidity, mortality, and socioeconomic burden. The application of machine learning algorithms in combination with weighted gene co-expression network analysis (WGCNA) can be used to screen genes, therefore, we aimed to screen for potential biomarkers associated with AF development using this integrated bioinformatics approach. Methods: On the basis of the AF endocardium gene expression profiles GSE79768 and GSE115574 from the Gene Expression Omnibus database, differentially expressed genes (DEGs) between AF and sinus rhythm samples were identified. DEGs enrichment analysis and transcription factor screening were then performed. Hub genes for AF were screened using WGCNA and machine learning algorithms, and the diagnostic accuracy was assessed by the receiver operating characteristic (ROC) curves. GSE41177 was used as the validation set for verification. Subsequently, we identified the specific signaling pathways in which the key biomarkers were involved, using gene set enrichment analysis and reverse prediction of mRNA-miRNA interaction pairs. Finally, we explored the associations between the hub genes and immune microenvironment and immune regulation. Results: Fifty-seven DEGs were identified, and the two hub genes, hypoxia inducible factor 1 subunit alpha inhibitor (HIF1AN) and mitochondrial inner membrane protein MPV17 (MPV17), were screened using WGCNA combined with machine learning algorithms. The areas under the receiver operating characteristic curves for MPV17 and HIF1AN validated that two genes predicted AF development, and the differential expression of the hub genes was verified in the external validation dataset. Enrichment analysis showed that MPV17 and HIF1AN affect mitochondrial dysfunction, oxidative stress, gap junctions, and other signaling pathway functions. Immune cell infiltration and immunomodulatory correlation analyses showed that MPV17 and HIF1AN are strongly correlated with the content of immune cells and significantly correlated with HLA expression. Conclusion: The identification of hub genes associated with AF using WGCNA combined with machine learning algorithms and their correlation with immune cells and immune gene expression can elucidate the molecular mechanisms underlying AF occurrence. This may further identify more accurate and effective biomarkers and therapeutic targets for the diagnosis and treatment of AF. [ABSTRACT FROM AUTHOR]

SOX9 plays a crucial role in the male reproductive system, brain, and kidneys. In this study, we firstly analyzed the complete cDNA sequence and expression patterns for SOX9 from Gekko japonicus SOX9 (gjSOX9), carried out bioinformatic analyses of physiochemical properties, structure, and phylogenetic evolution, and compared these with other members of the gjSOX family. The results indicate that gjSOX9 cDNA comprises 1895 bp with a 1482 bp ORF encoding 494aa. gjSOX9 was not only expressed in various adult tissues but also exhibited a special spatiotemporal expression pattern in gonad tissues. gjSOX9 was predicted to be a hydrophilic nucleoprotein with a characteristic HMG-Box harboring a newly identified unique sequence, “YKYQPRRR”, only present in SOXE members. Among the 20 SOX9 orthologs, gjSOX9 shares the closest genetic relationships with Eublepharis macularius SOX9, Sphacrodactylus townsendi SOX9, and Hemicordylus capensis SOX9. gjSOX9 and gjSOX10 possessed identical physicochemical properties and subcellular locations and were tightly clustered with gjSOX8 in the SOXE group. Sixteen gjSOX family members were divided into six groups: SOXB, C, D, E, F, and H with gjSOX8, 9, and 10 in SOXE among 150 SOX homologs. Collectively, the available data in this study not only facilitate a deep exploration of the functions and molecular regulation mechanisms of the gjSOX9 and gjSOX families in G. japonicus but also contribute to basic research regarding the origin and evolution of SOX9 homologs or even sex-determination mode in reptiles.

Background: Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS. Methods: To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram. Results: There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs. Conclusion: Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Malignant gliomas are the most prevalent and fatal types of primary malignant brain tumors with poor prognosis. Protein phosphatase 3 catalytic subunit beta (PPP3CB) is a pivotal constituent of the Ca2+/calmodulin-dependent serine/threonine protein phosphatases and widely expressed in brain. We aimed at identifying whether PPP3CB has potential in being a novel biomarker of malignant gliomas, bringing new insights to clinical management and therapy. Methods: Transcriptomes and clinical data of Glioblastoma (GBM) and low-grade glioma (LGG) samples were downloaded from TCGA and CGGA. We first explored the expressional and survival features of tumor tissues. Then, PPP3CB-associated genes were identified and their functional pathways were explored through GSEA analyses. Western blotting was conducted to modify PPP3CB expression. Samples of glioma patients and healthy controls were collected and immunohistochemistry (IHC) staining was performed to detect protein level. Further, we carried out an immune infiltration analysis, explored the correlation between PPP3CB and immune checkpoint genes, as well as to assessed the tumor mutation burden (TMB) and tumor microenvironment score (TMEscore) of PPP3CB. Results: PPP3CB expression in malignant glioma tissues was significantly downregulated and was considered an independent prognostic factor. Several functional pathways were observed through functional pathway analyses. PPP3CB's expression was strongly related to the infiltration of various immune cells and expression of key immune checkpoint genes. PPP3CB expression in high-grade gliomas was significantly lower, affecting glioma cells' proliferation and apoptosis in vitro. Conclusion: PPP3CB was a potential biomarker for the diagnosis and prognosis of malignant gliomas.

Abstract Background Rheumatoid arthritis (RA) is often accompanied by a common extra-articular manifestation known as RA-related usual interstitial pneumonia (RA-UIP), which is associated with a poor prognosis. However, the mechanism remains unclear. To identify potential mechanisms, we conducted bioinformatics analysis based on high-throughput sequencing of the Gene Expression Omnibus (GEO) database. Results Weighted gene co-expression network analysis (WGCNA) analysis identified 2 RA-positive related modules and 4 idiopathic pulmonary fibrosis (IPF)-positive related modules. A total of 553 overlapped differentially expressed genes (DEG) were obtained, of which 144 in the above modules were further analyzed. The biological process of “oxidative phosphorylation” was found to be the most relevant with both RA and IPF. Additionally, 498 up-regulated genes in lung tissues of RA-UIP were screened out and enriched by 7 clusters, of which 3 were closely related to immune regulation. The analysis of immune infiltration showed a characteristic distribution of peripheral immune cells in RA-UIP, compared with IPF-UIP in lung tissues. Conclusions These results describe the complex molecular and functional landscape of RA-UIP, which will help illustrate the molecular pathological mechanism of RA-UIP and identify new biomarkers and therapeutic targets for RA-UIP in the future.

Zinc finger protein (ZFP) transcription factors play a pivotal role in regulating plant growth, development, and response to biotic and abiotic stresses. Although extensively characterized in model organisms, these genes have yet to be reported in bamboo plants, and their expression information is lacking. Therefore, we identified 21 B-box (BBX) genes from a transcriptome analysis of Bambusa pervariabilis × Dendrocalamopsis grandis. Consequently, multiple sequence alignments and an analysis of conserved motifs showed that they all had highly similar structures. The BBX genes were divided into four subgroups according to their phylogenetic relationships and conserved domains. A GO analysis predicted multiple functions of the BBX genes in photomorphogenesis, metabolic processes, and biological regulation. We assessed the expression profiles of 21 BBX genes via qRT-PCR under different adversity conditions. Among them, eight genes were significantly up-regulated under water deficit stress (BBX4, BBX10, BBX11, BBX14, BBX15, BBX16, BBX17, and BBX21), nine under salt stress (BBX2, BBX3, BBX7, BBX9, BBX10, BBX12, BBX15, BBX16, and BBX21), twelve under cold stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21), and twelve under pathogen infestation stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21). Three genes (BBX10, BBX15, and BBX21) were significantly up-regulated under both biotic and abiotic stresses. These results suggest that the BBX gene family is integral to plant growth, development, and response to multivariate stresses. In conclusion, we have comprehensively analyzed the BDBBX genes under various adversity stress conditions, thus providing valuable information for further functional studies of this gene family. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is often accompanied by a common extra-articular manifestation known as RA-related usual interstitial pneumonia (RA-UIP), which is associated with a poor prognosis. However, the mechanism remains unclear. To identify potential mechanisms, we conducted bioinformatics analysis based on high-throughput sequencing of the Gene Expression Omnibus (GEO) database. Results: Weighted gene co-expression network analysis (WGCNA) analysis identified 2 RA-positive related modules and 4 idiopathic pulmonary fibrosis (IPF)-positive related modules. A total of 553 overlapped differentially expressed genes (DEG) were obtained, of which 144 in the above modules were further analyzed. The biological process of "oxidative phosphorylation" was found to be the most relevant with both RA and IPF. Additionally, 498 up-regulated genes in lung tissues of RA-UIP were screened out and enriched by 7 clusters, of which 3 were closely related to immune regulation. The analysis of immune infiltration showed a characteristic distribution of peripheral immune cells in RA-UIP, compared with IPF-UIP in lung tissues. Conclusions: These results describe the complex molecular and functional landscape of RA-UIP, which will help illustrate the molecular pathological mechanism of RA-UIP and identify new biomarkers and therapeutic targets for RA-UIP in the future. [ABSTRACT FROM AUTHOR]

One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNATF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc degeneration (IVDD), which contributes to stenosis of the spinal segment, commonly causes lower back pain. The process of IVDD degradation entails gradual structural adjustments accompanied by extreme transformations in metabolic homeostasis. However, the molecular and cellular mechanisms associated with IVDD are poorly understood.Methods: The RNA-sequencing datasets GSE34095 and GSE56081 were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (DEGs) were identified from these gene sets. The protein–protein interaction (PPI) network was established and visualized using the STRING database and Cytoscape software, and the key functional modules of ferroptosis-related genes were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Weighted gene co-expression network analysis (WGCNA), immune infiltration analysis in the GEO database, and other GSE series were used as validation datasets. The xCELL algorithm was performed to investigate the immune cell infiltration differences between the degenerated IVDD and control groups.Results: The major genes involved in nucleus pulposus tissue immune infiltration and ferroptosis-related genes were mined by bioinformatics analysis. A total of 3,056 DEGs were obtained between the IVDD tissue and control groups. The DEGs were enriched in the cell cycle; apoptosis; necroptosis; and the PI3K-Akt, Hippo, and HIF-1 signaling pathways. PCR and Western blot techniques were utilized to confirm the differential ferroptosis-related genes. The results indicated that the protein expression levels of NCOA4 and PCBP1 were elevated, while the protein expression level of GPX4 was reduced in NPCs following IL-1β treatment. Our study has found that severe disc tissue degeneration leads to a noteworthy increase in the expression of CD8A in naive T cells, CCR7 in memory CD4+ cells, GZMB in natural killer (NK) cells, and CD163 and CD45 in macrophages.Conclusion: Our data demonstrate that ferroptosis occurs in IVDD, suggesting that ferroptosis may also increase IVDD improvement by triggering immune infiltration. This work was conducted to further understand IVDD pathogenesis and identify new treatment strategies.

Highlights Breast cancer stem cells play a significant role in the recurrence of the disease or even the development of secondary tumors. SPARC, INHBA, FN1, and GBA genes play a significant role in breast cancer stem cells. hsa miR-9.5p, hsa miR-203.3p, and hsa miR-429. associated with breast cancer stem cells can be detected in human secretions.

Abstract Background Coronavirus disease 2019 (COVID-19) caused a series of biological changes in cancer patients which have rendered the original treatment ineffective and increased the difficulty of clinical treatment. However, the clinical treatment for cancer patients infected with COVID-19 is currently unavailable. Since bioinformatics is an effective method to understand undiscovered biological functions, pharmacological targets, and therapeutic mechanisms. The aim of this study was to investigate the influence of COVID-19 infection in cancer patients and to search the potential treatments. Methods Firstly, we obtained the COVID-19-associated genes from seven databases and analyzed the cancer pathogenic genes from Gene Expression Omnibus (GEO) databases, respectively. The Cancer/COVID-19-associated genes were shown by Venn analyses. Moreover, we demonstrated the signaling pathways and biological functions of pathogenic genes in Cancer/COVID-19. Results We identified that Go-Ichi-Ni-San complex subunit 1 (GINS1) is the potential therapeutic target in Cancer/COVID-19 by GEPIA. The high expression of GINS1 was not only promoting the development of cancers but also affecting their prognosis. Furthermore, eight potential compounds of Cancer/COVID-19 were identified from CMap and molecular docking analysis. Conclusion We revealed the GINS1 is a potential therapeutic target in cancer patients infected with COVID-19 for the first time, as COVID-19 will be a severe and prolonged pandemic. However, the findings have not been verified actually cancer patients infected with COVID-19, and further studies are needed to demonstrate the functions of GINS1 and the clinical treatment of the compounds.

Equine coronavirus (ECoV) was first identified in the USA and has been previously described in several countries. In order to test the presence of ECoV in China, we collected 51 small intestinal samples from donkey foals with diarrhoea from a donkey farm in Shandong Province, China between August 2020 and April 2021. Two samples tested positive for ECoV and full-length genome sequences were successfully obtained using next-generation sequencing, one of which was further confirmed by Sanger sequencing. The two strains shared 100% sequence identity at the scale of whole genome. Bioinformatics analyses further showed that the two Chinese strains represent a novel genetic variant of ECoV and shared the highest sequence identity of 97.05% with the first identified ECoV strain – NC99. In addition, it may be a recombinant, with the recombination region around the NS2 gene. To our knowledge, this is the first documented report of ECoV in China, highlighting its risk to horse/donkey breeding. In addition, its potential risk to public health also warrants further investigation.

Background: Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls. Methods: In this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or randomeffects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls. Results: A total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns. Conclusions: The current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations. [ABSTRACT FROM AUTHOR]

Introduction: The increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world's health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients. Methods: We downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways. Results: By analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations. Discussion: In conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD. [ABSTRACT FROM AUTHOR]

Background: Epicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated. Methods: To identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining. Results: Compared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients. Conclusion: EAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms. Methods Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug’s therapeutic targets and potential mechanisms for anti-LUAD/COVID-19. Results We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusions This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.

De-Bin Liu,1,&ast; You-Fu He,2– 4,&ast; Gui-Jian Chen,1 Hua Huang,1 Xu-Ling Xie,1 Wan-Jun Lin,1 Zhi-Jian Peng1 1Department of Cardiology, The Second People’s Hospital of Shantou, Shantou, Guangdong Province, People’s Republic of China; 2Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, People’s Republic of China; 3Guizhou Provincial Cardiovascular Disease Clinical Medicine Research Center, Guiyang, Guizhou Province, People’s Republic of China; 4Medical College, Guizhou University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jian Peng, Department of Cardiology, The Second People’s Hospital of Shantou, Shantou, 515000, Guangdong Province, People’s Republic of China, Tel +86 18316056382, Fax +86-754 88983534, Email 983247770@qq.comBackground: Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circRNAs play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in AD based on the circRNA-associated competing endogenous RNA (ceRNA) network.Methods: Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified by bioinformatics analysis. CircRNA–miRNA–mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to predict the potential functions of circRNA-associated ceRNA network. RNA was isolated from human arterial blood samples after which qRT-PCR was performed to confirm the DERNAs.Results: We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) (adjusted P-value < 0.05 and | log2FC | > 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix receptor interaction signaling pathways. Simultaneously, the present study constructed a ceRNA network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1). qRT-PCR demonstrated that hsa_circRNA_082317 and ITGA5 were significantly up-regulated, and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3).Conclusion: This is the first study to demonstrate the circRNA-associated ceRNA network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression and thus may serve as potential biomarkers for the diagnosis and treatment of AD.Keywords: circRNA, miRNA, mRNA, ceRNA, aortic dissection, bioinformatics analyses

Elevated polyamine levels are required for tumor transformation and development; however, expression patterns of polyamines and their diagnostic potential have not been investigated in oral squamous cell carcinoma (OSCC), and its impact on prognosis has yet to be determined. A total of 440 OSCC samples and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Consensus clustering was conducted to classify OSCC patients into two subgroups based on the expression of the 17 polyamine regulators. Polyamine-related differentially expressed genes (PARDEGs) among distinct polyamine clusters were determined. To create a prognostic model, PARDEGs were examined in the training cohorts using univariate-Lasso-multivariate Cox regression analyses. Six prognostic genes, namely, “CKS2,” “RIMS3,” “TRAC,” “FMOD,” CALML5,” and “SPINK7,” were identified and applied to develop a predictive model for OSCC. According to the median risk score, the patients were split into high-risk and low-risk groups. The predictive performance of the six gene models was proven by the ROC curve analysis of the training and validation cohorts. Kaplan–Meier curves revealed that the high-risk group had poorer prognosis. Furthermore, the low-risk group was more susceptible to four chemotherapy drugs according to the IC50 of the samples computed by the “pRRophetic” package. The correlation between the risk scores and the proportion of immune cells was calculated. Meanwhile, the tumor mutational burden (TMB) value of the high-risk group was higher. Real-time quantitative polymerase chain reaction was applied to verify the genes constructing the model. The possible connections of the six genes with various immune cell infiltration and therapeutic markers were anticipated. In conclusion, we identified a polyamine-related prognostic signature, and six novel biomarkers in OSCC, which may provide insights to identify new treatment targets for OSCC.

Background: Breast cancer is one of the most common cancers in women, and many people get it every year. The cancer stem cells are maybe crucial role to exacerbates and relapse the breast cancer. Therefore, finding biomarkers in human secretions can be an suitable solution for early detection and neo adjuvant therapy. This study aimed to investigate the molecular events related to the cancer stem cells in breast cancer, after which we nominated a suitable MicroRNAs participates in breast cancer pathogenesis. Methods: In this study, we investigated the relationship between molecular pathways using a bioinformatics approach. First, we selected the appropriate RNA-Seq datasets from the GEO database. We used Enrichr, KEGG, and Shiny GO databases to evaluate the signal pathways and gene ontology after isolating the gene expression profiles. In the next step, we used the STRING database to assess the protein network, and we used the Targetscan database to nominate the MicroRNA. Results: 510 high-expression genes and 460 low-expression genes were associated with breast cancer and the cancer stem cells. Highly expressed genes were involved in the cell cycle and cellular aging pathways. On the other hand, low-expression genes were involved in the RNA transports, spliceosome, and apoptosis pathways. After evaluating the ontology of genes and the relationship between proteins, high-expression SPARC, INHBA, FN1, and GBA proteins were nominated. In the next section, the MicroRNAs related to these genes were hsa miR-9.5p, hsa miR-203.3p, and hsa miR-429. Conclusion: In general, we examined more closely and more the relationship between the cancer stem cells pathway and breast cancer using a regular and accurate bioinformatics framework. Finally, we nominated suitable MicroRNAs that were involved in breast cancer stem cells. Highlights: Breast cancer stem cells play a significant role in the recurrence of the disease or even the development of secondary tumors. SPARC, INHBA, FN1, and GBA genes play a significant role in breast cancer stem cells. hsa miR-9.5p, hsa miR-203.3p, and hsa miR-429. associated with breast cancer stem cells can be detected in human secretions. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with a poor prognosis and lack of effective biomarkers. We demonstrated, using bioinformatics analyses, that the leucine-rich repeat-containing 8A (LRRC8A) can affect the prognosis of patients with PAAD. In addition, experiments in vitro showed shRNA of LRRC8A can significantly affect the hallmarks of PAAD, including cell proliferation, cell migration, drug resistance, and immune infiltration. Collectively, our data suggest that LRRC8A could be a promising prognostic biomarker and therapeutic target for PAAD. Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B–E). VRAC heterogeneous complex is implicated in each of the six "hallmarks of cancer" and represents a novel therapeutic target for cancer. In this study, LRRC8A was speculated to be a promising prognostic biomarker and therapeutic target for PAAD based on a series of bioinformatics analyses. Additional cell experiments and immunohistochemical assays demonstrated that LRRC8A can affect the prognosis of PAAD and is correlated to cell proliferation, cell migration, drug resistance, and immune infiltration. Functional analysis indicated that LRRC8A influences the progression and prognosis of patients with PAAD by the regulation of CD8+ T cells immune infiltration. Taken together, these results can help in the design of new therapeutic drugs for patients with PAAD. [ABSTRACT FROM AUTHOR]

A comparative quali-quantitative study of the peel extracts of eight Punica granatum cultivars obtained from underexploited areas of South Italy was carried out in order to valorize them as health-promoting by-products. The results showed that all of the samples possessed 45 ellagitannins, consisting mainly of polyhydroxyphenoyls; 10 flavonoids, belonging to flavonol, flavone, and catechin classes; and 2 anthocyanins. The most representative compounds underwent quantification through a LC-MS/MS multiple reaction monitoring (MRM)-based method; their qualitative profile was almost superimposable, while variability in the quantitative phenolic content was observed. The antioxidant activity was investigated using cell-free and cell-based assays. The in vitro anti-inflammatory potential was also studied by monitoring three typical markers of inflammation (IL-1β, IL-6, and TNF-α). Moderate differences in both activities were observed between the cultivars. Results showed that all of the investigated peels have a potential use as healthy bioactive phytocomplexes due to the interesting antioxidant and anti-inflammatory activities; in particular from the bioinformatic approaches a series of compounds, including galloyl-, pedunculagin- and ellagic acid-based, were found to be highly correlated with bioactivity of the extracts. Finally, the bioactivities showed by a Campanian local cultivar, ‘Granato di Aiello del Sabato’, could promote its cultivation by local farmers and germplasm conservation. [ABSTRACT FROM AUTHOR]

In order to analyze the function of PacC, a pH-signaling transcription factor of Penicillium italicum, which was a postharvest pathogen of citrus fruits. The gene had 1921 bp cDNA and an intron, which encoded 636 amino acids and contains three typical zinc finger domains of transcription factors. Phylogenetic tree analysis showed that the PacC was clustered with Penicillium digitatum and Penicillium chrysogenum. In vitro test, the PacC gene was stably expressed during the growth of P.italicum. The pH of the medium affected the growth of P.italicum and the expression level of PacC, and the expression level was significantly down-regulated under acidic conditions(P

Zinc finger protein (ZFP) transcription factors play a pivotal role in regulating plant growth, development, and response to biotic and abiotic stresses. Although extensively characterized in model organisms, these genes have yet to be reported in bamboo plants, and their expression information is lacking. Therefore, we identified 21 B-box (BBX) genes from a transcriptome analysis of Bambusa pervariabilis × Dendrocalamopsis grandis. Consequently, multiple sequence alignments and an analysis of conserved motifs showed that they all had highly similar structures. The BBX genes were divided into four subgroups according to their phylogenetic relationships and conserved domains. A GO analysis predicted multiple functions of the BBX genes in photomorphogenesis, metabolic processes, and biological regulation. We assessed the expression profiles of 21 BBX genes via qRT-PCR under different adversity conditions. Among them, eight genes were significantly up-regulated under water deficit stress (BBX4, BBX10, BBX11, BBX14, BBX15, BBX16, BBX17, and BBX21), nine under salt stress (BBX2, BBX3, BBX7, BBX9, BBX10, BBX12, BBX15, BBX16, and BBX21), twelve under cold stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21), and twelve under pathogen infestation stress (BBX1, BBX2, BBX4, BBX7, BBX10, BBX12, BBX14, BBX15, BBX17, BBX18, BBX19, and BBX21). Three genes (BBX10, BBX15, and BBX21) were significantly up-regulated under both biotic and abiotic stresses. These results suggest that the BBX gene family is integral to plant growth, development, and response to multivariate stresses. In conclusion, we have comprehensively analyzed the BDBBX genes under various adversity stress conditions, thus providing valuable information for further functional studies of this gene family.

Background: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear. Methods: We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein-protein interaction (PPI) analysis, transcription factor (TF)-gene interaction network analysis, transcription factor-miRNA co-regulatory network analysis, and candidate drug analysis prediction. Results: We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL- 1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF-gene and TF-miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted. Conclusion: This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future. [ABSTRACT FROM AUTHOR]

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of known regeneration associated transcription factors, including Jun, Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hifla, Ppary, Asclla, Srf, and Ctcf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of novel candidate transcription factors alone or in combination promotes axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis highlights that transcription factor interaction and chromatin architecture play important roles as a regulator of axon regeneration. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is associated with different infections such as urinary tract infections (UTIs). The increased antibiotic resistance reaches the need to develop vaccine against the infections. In the present study, bioinformatics approaches were applied to design a novel multi-epitope of PcrV and OmpE from P. aeruginosa . The raised antibody against the multi-epitope was evaluated and challenge experiment was done to evaluate the efficacy of the multi-epitope. The results of epitope mapping of B-cells indicated 8 regions for PcrV and OmpE. The predicted 3D structure showed C-score = -1 and Z-score = -8.12. Molecular docking indicated high interaction between residues of Toll-like receptor 2 (TLR2) and TLR4 with the multi-epitope. The results of in silico simulation of the immune responses showed elevated levels of B-cell, T-cell, and memory cells. PcrV, OmpE, and the multi-epitope were expressed in pET28a- E. coli BL21 (DE3) and purified by Nickel columns. Our findings indicated that the sera collected from immunized rabbits with the multi-epitope reacted with the multi-epitope, PcrV, and OmpE in western blot. According to the ELISA results, the antibody developed against the multi-epitope showed cross-reactivity with individual proteins PcrV and OmpE. The level of antibody raised against the multi-epitope was significantly higher than the antibody reacted with PcrV or OmpE alone in ELISA. The challenge results confirmed that the load of bacteria was decreased in immunized rabbits as compared to the control. The results present the multi-epitope composed of PcrV and OmpE as a promising candidate against P. aeruginosa . Further evaluations are under investigation in animal model.Communicated by Ramaswamy H. Sarma.

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons in vivo and that all neuronal subtypes are represented. This eDRG neuronal culture does not contain other non-neuronal cell types. Next, we performed RNA sequencing at different time points after in vitro axotomy. Analysis of differentially expressed genes revealed upregulation of known regeneration associated transcription factors, including Jun, Atf3 and Rest, paralleling the axon injury response in vivo. Analysis of transcription factor binding sites in differentially expressed genes revealed other known transcription factors promoting axon regeneration, such as Myc, Hif1α, Pparγ, Ascl1a, Srf, and Ctcf, as well as other transcription factors not yet characterized in axon regeneration. We next tested if overexpression of novel candidate transcription factors alone or in combination promotes axon regeneration in vitro. Our results demonstrate that expression of Ctcf with Yy1 or E2f2 enhances in vitro axon regeneration. Our analysis highlights that transcription factor interaction and chromatin architecture play important roles as a regulator of axon regeneration.

ObjectiveInflammation plays an important role in the pathophysiology of ischemic cardiomyopathy (ICM). We aimed to identify potential biomarkers of inflammation-related genes for ICM and build a model based on the potential biomarkers for the diagnosis of ICM.Materials and methodsThe microarray datasets and RNA-Sequencing datasets of human ICM were downloaded from the Gene Expression Omnibus database. We integrated 8 microarray datasets via the SVA package to screen the differentially expressed genes (DEGs) between ICM and non-failing control samples, then the differentially expressed inflammation-related genes (DEIRGs) were identified. The least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were utilized to screen the potential diagnostic biomarkers from the DEIRGs. The potential biomarkers were validated in the RNA-Sequencing datasets and the functional experiment of the ICM rat, respectively. A nomogram was established based on the potential biomarkers and evaluated via the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and Clinical impact curve (CIC).Results64 DEGs and 19 DEIRGs were identified, respectively. 5 potential biomarkers (SERPINA3, FCN3, PTN, CD163, and SCUBE2) were ultimately selected. The validation results showed that each of these five potential biomarkers showed good discriminant power for ICM, and their expression trends were consistent with the bioinformatics results. The results of AUC, calibration curve, DCA, and CIC showed that the nomogram demonstrated good performance, calibration, and clinical utility.ConclusionSERPINA3, FCN3, PTN, CD163, and SCUBE2 were identified as potential biomarkers associated with the inflammatory response to ICM. The proposed nomogram could potentially provide clinicians with a helpful tool to the diagnosis and treatment of ICM from an inflammatory perspective.

Background: Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms.Methods: Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug's therapeutic targets and potential mechanisms for anti-LUAD/COVID-19.Results: We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusions: This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro. [ABSTRACT FROM AUTHOR]

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD. Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking. Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking. Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD.Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking.Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking.Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.

[Display omitted] • Acute pre-treatment with caffeine has an anti-inflammatory effect characterized by the negative regulation of the expression of the gene encoding the pro-inflammatory cytokine Il-1β in the brain regions of the striatum and hippocampus. • Treatment with caffeine and LPS alters the epigenetic scenario by modifying the expression pattern of DNA-modifying enzymes with a consequent change in the percentages of 5-meC and 5-hmeC marks of the Adora1 and Adora2A genes in the CNS. • The neuroprotective effect of caffeine pretreatment is mediated by the differential modulation of the expression of adenosine receptors in the striatum and hippocampus and has the Adora2B gene as a key point in the connection between the expanded networks of the Adora1 and Adora2A genes. Caffeine has been extensively studied in the context of CNS pathologies as many researchers have shown that consuming it reduces pro-inflammatory biomarkers, potentially delaying the progression of neurodegenerative pathologies. Several lines of evidence suggest that adenosine receptors, especially A 1 and A 2 A receptors, are the main targets of its neuroprotective action. We found that caffeine pretreatment 15 min before LPS administration reduced the expression of Il1b in the hippocampus and striatum. The harmful modulation of caffeine-induced inflammatory response involved the downregulation of the expression of A 2 A receptors, especially in the hippocampus. Caffeine treatment alone promoted the downregulation of the adenosinergic receptor Adora2A; however, this promotion effect was reversed by LPS. Although administering caffeine increased the expression of the enzymes DNA methyltransferases 1 and 3A and decreased the expression of the demethylase enzyme Tet1, this effect was reversed by LPS in the hippocampus of mice that were administered Caffeine + LPS, relative to the basal condition; no significant differences were observed in the methylation status of the promoter regions of adenosine receptors. Finally, the bioinformatics analysis of the expanded network demonstrated the following results: the Adora2B gene connects the extended networks of the adenosine receptors Adora1 and Adora2A; the Mapk3 and Esr1 genes connect the extended Adora1 network; the Mapk4 and Arrb2 genes connect the extended Adora2A network with the extended network of the proinflammatory cytokine Il1β. These results indicated that the anti-inflammatory effects of acute caffeine administration in the hippocampus may be mediated by a complex network of interdependencies between the Adora2B and Adora2A genes. [ABSTRACT FROM AUTHOR]

Autophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein–protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited. Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction. Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions. Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease. [ABSTRACT FROM AUTHOR]

Abstract Background Non-small cell lung cancer (NSCLC) is the major type of lung cancer with high morbidity and poor prognosis. Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), has been clinically applied for NSCLC treatment. Nevertheless, the erlotinib acquired resistance of NSCLC occurs inevitably in recent years. Methods Through analyzing two microarray datasets, erlotinib resistant NSCLC cells microarray (GSE80344) and NSCLC tissue microarray (GSE19188), the differentially expressed genes (DEGs) were screened via R language. DEGs were then functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which up-regulated more than 2-folds in both datasets were further functionally analyzed by Oncomine, GeneMANIA, R2, Coremine, and FunRich. Results We found that matrix metalloproteinase 1 (MMP1) may confer the erlotinib therapeutic resistance in NSCLC. MMP1 highly expressed in erlotinib-resistant cells and NSCLC tissues, and it associated with poor overall survival. In addition, MMP1 may be associated with COPS5 and be involve in an increasing transcription factors HOXA9 and PBX1 in erlotinib resistance. Conclusions Generally, these results demonstrated that MMP1 may play a crucial role in erlotinib resistance in NSCLC, and MMP1 could be a prognostic biomarker for erlotinib treatment.

Abstract Background Non-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA. Methods In this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs. Results A total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway. Conclusions This is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR

Introduction: The rapid spread of plasmid-mediated tet(X4) conferring high tigecycline resistance poses a significant threat to public health. Escherichia coli as the most common pathogen which carries tet(X4) has been widely disseminated in China. Thus, comprehensive investigations are required to understand the mechanism of transmission of tet(X4) -positive E. coli ., Methods: In this study, a total of 775 nonduplicate samples were collected in Guangdong, China from 2019 to 2020. We screened for tet(X4) -positive E. coli by PCR amplification and species identification. Furthermore, we analyzed the phylogenetics and genetic context of tet(X4) -positive E. coli through whole-genome sequencing and long-reads sequencing., Results: Overall, 146 (18.84%) tet(X4) -positive E. coli were isolated, comprising 2 isolates from humans and 144 isolates from pigs. The majority of tet(X4) -positive E. coli exhibited resistance to multiple antibiotics but all of them were susceptible to amikacin and colistin. Phylogenetic analysis showed that ST877, ST871, and ST195 emerged as the predominant sequence types in tet(X4) -positive E. coli . Further analysis revealed various genetic environments associated with the horizontal transfer of tet(X4) . Notably, a 100-kbp large fragment insertion was discovered downstream of tet(X4) , containing a replicon and a 40-kbp gene cluster for the bacterial type IV secretion system., Discussion: The high colonization rate of tet(X4) -positive E. coli in animals suggests that colonization as a key factor in its dissemination to humans. Diverse genetic context may contribute to the transfer of tet(X4) . Our findings underline the urgent need for controlling the spread of plasmid-mediated tigecycline resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shao, Wu, Li, He, Chen, Sun, Yang, Feng, Zhang, Yan, Dai, Tian and Zhong.)

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B–E). VRAC heterogeneous complex is implicated in each of the six “hallmarks of cancer” and represents a novel therapeutic target for cancer. In this study, LRRC8A was speculated to be a promising prognostic biomarker and therapeutic target for PAAD based on a series of bioinformatics analyses. Additional cell experiments and immunohistochemical assays demonstrated that LRRC8A can affect the prognosis of PAAD and is correlated to cell proliferation, cell migration, drug resistance, and immune infiltration. Functional analysis indicated that LRRC8A influences the progression and prognosis of patients with PAAD by the regulation of CD8+ T cells immune infiltration. Taken together, these results can help in the design of new therapeutic drugs for patients with PAAD.

Background: Luminal breast cancer (BC) is the most frequent subtype accounting for more than 70% of BC. LncRNAs, a class of non-coding RNAs with more than 200 nucleotides, are involved in a variety of cellular processes and biological functions. Abberant expression is related to the development of various cancers, such as breast cancer. LINC01133, ZEB1-AS1, and ABHD11-AS1 were reported to be dysregulated in different cancers. However, their expression level in luminal BC remains poorly known. The aim of the present study was to evaluate the potential roles of these lncRNAs in BC, especially in luminal subtypes.Methods: A comprehensive analysis was performed using the Lnc2Cancer database to identify novel cancer-associated lncRNA candidates. After conducting a literature review, three novel lncRNAs named LINC01133, ZEB1-AS1, and ABHD11-AS1 were chosen as target genes of the present study. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of the mentioned lncRNAs in both luminal BC tissues and cell lines. Then, the correlation of the three mentioned lncRNAs expression with clinicopathological characteristics of the patients was studied. Moreover, several datasets were used to discover the potential roles and functions of LINC01133, ZEB1-AS1 and ABHD11-AS1 in luminal subtype of BC.Results: According to the qRT-PCR assay, the expression levels of LINC01133 and ZEB1-AS1 were decreased in luminal BC tissues and cell lines. On the other hand, ABHD11-AS1 was upregulated in the above-mentioned samples. The expression levels of LINC01133, ZEB1-AS1, and ABHD11-AS1 were not associated with any of the clinical features. Also, the results obtained from the bioinformatics analyses were consistent with qRT-PCR data. Functional annotation of the co-expressed genes with the target lncRNAs, protein-protein interactions and significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways across luminal BC were also obtained using bioinformatics analysis.Conclusions: Taken together, our findings disclosed the dysregulation of LINC01133, ZEB1-AS1, and ABHD11-AS1 in luminal BC. It was revealed that LINC01133 and ZEB1-AS1 expression was significantly downregulated in luminal BC tissues and cell lines, while ABHD11-AS1 was upregulated considerably in the mentioned tissues and cell lines. Also, bioinformatics and systems biology analyses have helped to identify the possible role of these lncRNAs in luminal BC. However, further analysis is needed to confirm the current findings. [ABSTRACT FROM AUTHOR]

Background: The outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection. Methods: To further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents. Results: We explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone. Conclusions: This study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to identify the key pathway and immune cells for hypertrophic cardiomyopathy (HCM) via bioinformatics analyses of public datasets and evaluate the significance of immune infiltration in the pathogenesis of HCM.Methods: Expressional profiling from two public datasets (GSE36961 and GSE141910) of human HCM and healthy control cardiac tissues was obtained from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were then screened between HCM and healthy control cardiac tissues in parallel. Gene Ontology, pathway functional enrichment, and gene set enrichment analysis were performed using DAVID and GSEA application. The compositional patterns of immune and stromal cells in HCM and control cardiac tissues were estimated based on the merged data using xCell. Protein–protein interaction (PPI) network and module analyses were constructed by STRING and Cytoscape applications. Gender-based expressional differences analyses were also conducted to explore gender differences in HCM. GSE130036 and clinical samples were used for verification analyses.Results: A total of 310 DEGs were identified. Upregulated DEGs were mainly enriched in “adhesion” and “apoptotic process” in the biological process. As for the downregulated DEGs, “inflammatory response,” “innate immune response,” “phagosome,” and “JAK-STAT signaling pathway” were highly enriched. Immune infiltration analyses suggested that the scores of macrophages, monocytes, DC, Th1, Treg, and plasma cells in the HCM group were significantly decreased, while CD8+ T cells, basophils, fibroblasts, and platelets were significantly enriched. Module analyses revealed that STAT3, as the hub genes in HCM together with LYVE1+CD163+ macrophages, may play a key role in the pathogenesis of HCM while there were no obvious gender differences in the HCM samples from selected datasets. Verification analyses performed on GSE130036 and clinical samples showed a strong positive correlation (Spearman correlation = 0.7646) and a good co-localization relationship between LYVE1 and CD163, suggesting the potential function of LYVE1+CD163+ macrophages in maintaining the homeostasis of cardiac tissue.Conclusion: STAT3-related pathway and CD163+LYVE1+ macrophages were identified as the potential key pathway and immune cells in HCM and may serve as interesting targets for further in-depth research.

BackgroundThe outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection.MethodsTo further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents.ResultsWe explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone.ConclusionsThis study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.

Esophageal cancer (EC) is one of the deadliest cancers worldwide. However, reliable biomarkers for early diagnosis, or those for the prognosis of therapy, remain unfulfilled goals for its subtype esophageal squamous cell carcinoma (ESCC). The purpose of this study was to identify reliable biomarkers for the diagnosis and prognosis of ESCC by gene chip re-annotation technique and downstream bioinformatics analysis. In our research, the GSE53624 dataset was downloaded from the GEO database. Then, we reannotated the gene expression probe and obtained the gene expression matrix. Differential expressed genes (DEGs) were found by R packages and they were subjected to Gene Ontology enrichment analysis and protein–protein interaction (PPI) network construction. As a result, a total of 28,885 mRNA probes were reannotated, among which 210 down-regulated and 80 up-regulated DEGs were screened out. By combining these genes set in clinical prognosis information and Western blot analysis, we found four genes with diagnostic and prognostic significance, including MMP13, SPP1, MMP10, and COL1A1. Furthermore, markers of infiltrating immune cells exhibited different DEG-related immune infiltration patterns. [ABSTRACT FROM AUTHOR]

[Display omitted] • A differential variation in the rate of rearrangement by gene and by taxonomic order. • Crustacea and Chelicerata mitogenomes tend to be more rearranged compared to Myriapoda. • A high number of different gene orders are reported in the arthropod mitochondrial genome. • Ancestral gene order in each Subphylum and taxonomic order were postulate. In the species-rich Phylum Arthropoda, the mitochondrial genome is relatively well conserved both in terms of number and order of genes. However, specific clades have a 'typical' gene order that differs from the putative arthropod ancestral arrangement. The aim of this work was to compare the rate of mitochondrial gene rearrangements at inter- and intra-taxonomic levels in the Arthropoda and to postulate the most parsimonious ancestral orders representing the four major arthropod lineages. For this purpose, we performed a comparative genomic analysis of arthropod mitochondrial genomes available in the NCBI database. Using a combination of bioinformatics methods that examined mitochondrial gene rearrangements in 464 species of arthropods from three subphyla (Chelicerata, Myriapoda, and Crustacea [except Hexapoda, previously analyzed]), we observed differences in the rate of rearrangement within major lineages. A higher rate of mitochondrial genome rearrangement was observed in Crustacea and Chelicerata compared to Myriapoda. Likewise, early branching clades exhibit less variability in mitochondrial genome order than late branching clades, within each subphylum. We identified 'hot regions' in the mitochondrial genome of each studied subphylum, and postulated the most likely ancestral gene order in each subphylum and taxonomic order. Our work provides new evidence on the evolutionary dynamics of mitochondrial genome gene order in arthropods and new mitochondrial genome architectures in different taxonomic divisions within each major lineage of arthropods. [ABSTRACT FROM AUTHOR]

Abstract Background Annexins are involved in vesicle trafficking, cell proliferation and apoptosis, but their functional mechanisms in ovarian cancer remain unclear. In this study, we analyzed Annexins in ovarian cancer using different databases and selected Annexin A8 (ANXA8), which showed the greatest prognostic value, for subsequent validation in immunohistochemical (IHC) assays. Methods The mRNA expression levels, genetic variations, prognostic values and gene–gene interaction network of Annexins in ovarian cancer were analyzed using the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, Kaplan–Meier plotter and GeneMANIA database. ANXA8 was selected for analyzing the biological functions and pathways of its co-expressed genes, and its correlation with immune system responses via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and the TISIDB database, respectively. We validated the expression of ANXA8 in ovarian cancer via IHC assays and analyzed its correlation with clinicopathological parameters and prognosis. Results ANXA2/3/8/11 mRNA expression levels were significantly upregulated in ovarian cancer, and ANXA5/6/7 mRNA expression levels were significantly downregulated. Prognostic analysis suggested that significant correlations occurred between ANXA2/4/8/9 mRNA upregulation and poor overall survival, and between ANXA8/9/11 mRNA upregulation and poor progression-free survival in patients with ovarian serous tumors. Taken together, results suggested that ANXA8 was most closely associated with ovarian cancer tumorigenesis and progression. Further analyses indicated that ANXA8 may be involved in cell migration, cell adhesion, and vasculature development, as well as in the regulation of PI3K-Akt, focal adhesion, and proteoglycans. Additionally, ANXA8 expression was significantly correlated with lymphocytes and immunomodulators. The IHC results showed that ANXA8 expression was higher in the malignant tumor group than in the borderline and benign tumor groups and normal ovary group, and high ANXA8 expression was an independent risk factor for survival and prognosis of ovarian cancer patients (P = 0.013). Conclusions Members of the Annexin family display varying degrees of abnormal expressions in ovarian cancer. ANXA8 was significantly highly expressed in ovarian cancer, and high ANXA8 expression was significantly correlated with poor prognosis. Therefore, ANXA8 is a high candidate as a novel biomarker and therapeutic target for ovarian cancer.