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BMC Gastroenterology Jun 2024Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Hepatitis B virus (HBV) is one of the major causes of liver cirrhosis (LC) and HCC....
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Hepatitis B virus (HBV) is one of the major causes of liver cirrhosis (LC) and HCC. Therefore, the discovery of common markers for hepatitis B or LC and HCC is crucial for the prevention of HCC.
METHODS
Expressed genes for to chronic active hepaititis B (CAH-B), LC and HCC were obtained from the GEO and TCGA databases, and co-expressed genes were screened using Protein-protein interaction (PPI) networks, least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine - recursive feature elimination (SVM-RFE). The prognostic value of genes was assessed using Kaplan-Meier (KM) survival curves. Columnar line plots, calibration curves and receiver operating characteristic (ROC) curves of individual genes were used for evaluation. Validation was performed using GEO datasets. The association of these key genes with HCC clinical features was explored using the UALCAN database ( https://ualcan.path.uab.edu/index.html ).
RESULTS
Based on WGCNA analysis and TCGA database, the co-expressed genes (565) were screened. Moreover, the five algorithms of MCODE (ClusteringCoefficient, MCC, Degree, MNC, and DMNC) was used to select one of the most important and most closely linked clusters (the top 50 genes ranked). Using, LASSO regression model, RF model and SVM-RFE model, four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) were identified for subsequent research analysis. These 4 genes were highly expressed and associated with poor prognosis and clinical features in HCC patients.
CONCLUSION
These four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) may be common biomarkers for CAH-B and HCC or LC and HCC, promising to advance our understanding of the molecular basis of CAH-B/LC/HCC progression.
Topics: Carcinoma, Hepatocellular; Liver Neoplasms; Humans; Kinesins; Liver Cirrhosis; Computational Biology; Cell Cycle Proteins; Prognosis; Hepatitis B, Chronic; Biomarkers, Tumor; Protein Interaction Maps; Male; Kaplan-Meier Estimate; Support Vector Machine
PubMed: 38890649
DOI: 10.1186/s12876-024-03288-7 -
Cytokine Jun 2024Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality.
OBJECTIVES
Alveolar echinococcosis (AE) represents one of the deadliest helminthic infections, characterized by an insidious onset and high lethality.
METHODS
This study utilized the Gene Expression Omnibus (GEO) database, applied Weighted Correlation Network Analysis (WGCNA) and Differential Expression Analysis (DEA), and employed the Matthews Correlation Coefficient (MCC) to identify CCL17 and CCL19 as key genes in AE. Immunohistochemistry and immunofluorescence co-localization techniques were used to examine the expression of CCL17 and CCL19 in liver tissue lesions of AE patients. Additionally, a mouse model of multilocular echinococcus larvae infection was developed to study the temporal expression patterns of these genes, along with liver fibrosis and inflammatory responses.
RESULTS
The in vitro model simulating echinococcal larva infection mirrored the hepatic microenvironment post-infection with multilocular echinococcal tapeworms. Quantitative RT-PCR analysis showed that liver fibrosis occurred in AE patients, with proximal activation and increased expression of CCL17 and CCL19 over time post-infection. Notably, expression peaked during the late stages of infection. Similarly, F4/80, a macrophage marker, exhibited corresponding trends in expression. Upon stimulation of normal hepatocytes by vesicular larvae in cellular experiments, there was a significant increase in CCL17 and CCL19 expression at 12 h post-infection, mirroring the upregulation observed with F4/80.
CONCLUSION
CCL17 and CCL19 facilitate macrophage aggregation via the chemokine pathway and their increased expression correlates with the progression of infection, suggesting their potential as biomarkers for AE progression.
PubMed: 38875750
DOI: 10.1016/j.cyto.2024.156669 -
Annals of Human Biology Feb 2024Mitophagy and ferroptosis occur in intracerebral haemorrhage (ICH) but our understanding of mitophagy and ferroptosis-related genes remains incomplete.
BACKGROUND
Mitophagy and ferroptosis occur in intracerebral haemorrhage (ICH) but our understanding of mitophagy and ferroptosis-related genes remains incomplete.
AIM
This study aims to identify shared ICH genes for both processes.
METHODS
ICH differentially expressed mitophagy and ferroptosis-related genes (DEMFRGs) were sourced from the GEO database and literature. Enrichment analysis elucidated functions. Hub genes were selected via STRING, MCODE, and MCC algorithms in Cytoscape. miRNAs targeting hubs were predicted using miRWalk 3.0, forming a miRNA-hub gene network. Immune microenvironment variances were assessed with MCP and TIMER. Potential small molecules for ICH were forecasted CMap database.
RESULTS
64 DEMFRGs and ten hub genes potentially involved in various processes like ferroptosis, TNF signalling pathway, MAPK signalling pathway, and NF-kappa B signalling pathway were discovered. Several miRNAs were identified as shared targets of hub genes. The ICH group showed increased infiltration of monocytic lineage and myeloid dendritic cells compared to the Healthy group. Ten potential small molecule drugs (e.g. Zebularine, TWS-119, CG-930) were predicted CMap.
CONCLUSION
Several shared genes between mitophagy and ferroptosis potentially drive ICH progression TNF, MAPK, and NF-kappa B pathways. These results offer valuable insights for further exploring the connection between mitophagy, ferroptosis, and ICH.
Topics: Mitophagy; Ferroptosis; Cerebral Hemorrhage; Humans; Computational Biology; MicroRNAs; Gene Regulatory Networks
PubMed: 38863372
DOI: 10.1080/03014460.2024.2334719 -
Diagnostic Microbiology and Infectious... Jun 2024Sepsis is a highly lethal disease that poses a serious threat to human health. Increasing evidence indicates that neutrophil extracellular traps (NETs) are key factors...
Sepsis is a highly lethal disease that poses a serious threat to human health. Increasing evidence indicates that neutrophil extracellular traps (NETs) are key factors in the pathological progression of sepsis. This study aims to screen potential biomarkers for sepsis and delve into their regulatory function in the pathogenesis. We downloaded 6 microarray datasets from the Gene Expression Omnibus (GEO) database, with 4 as the training sets and 2 as the validation sets. NETs-related genes (NRGs) were obtained from relevant literature. Differential expression analysis was performed on four training sets separately. We intersected differentially expressed genes (DEGs) from the four training sets and NRGs, finally resulting in 19 NETs-related sepsis genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) unearthed that NETs-related sepsis genes were majorly abundant in functions and pathways such as defense response to bacterium and Neutrophil extracellular trap formation. Using the PPI network, the MCC algorithm, and the MCODE algorithm in the CytoHubba plugin, 7 sepsis hub genes (ELANE, TLR4, MPO, PADI4, CTSG, MMP9, S100A12) were identified. ROC curve for each Hub gene in the training and validation sets were plotted, which revealed that the Area Under Curve (AUC) values are all greater than 0.6, indicating good classification ability. A total of 349 miRNAs targeting Hub genes were predicted in the mirDIP database, and 620 lncRNAs targeting miRNAs were predicted in the ENCORI database. The ceRNA regulatory network was constructed using Cytoscape software. Finally, we employed the cMAP database to predict small molecular complexes as potentially effective drugs for the treatment of sepsis, such as chloroquine, harpagoside, and PD-123319. In conclusion, this project successfully identified 7 core genes, which may serve as promising candidates for novel sepsis biomarkers. Meanwhile, we constructed a related ceRNA network and predicted potential targeted drugs, providing potential therapeutic targets and treatment strategies for sepsis patients.
PubMed: 38852219
DOI: 10.1016/j.diagmicrobio.2024.116380 -
Antonie Van Leeuwenhoek Jun 2024Two alkaliphilic, Gram-stain-negative bacterial strains (MEB004 and MEB108) were isolated from water samples collected from Lonar lake, India. The phylogenetic analysis...
Two alkaliphilic, Gram-stain-negative bacterial strains (MEB004 and MEB108) were isolated from water samples collected from Lonar lake, India. The phylogenetic analysis of their 16S rRNA gene sequences showed the highest similarity to A. delamerensis DSM 18314 (98.4%), followed by A. amylolytica DSM 18337 and A. collagenimarina JCM 14267 (97.9%). The genome sizes of strains MEB004 and MEB108 were determined to be 3,858,702 and 4,029,814 bp, respectively, with genomic DNA G + C contents of 51.4 and 51.9%. Average Nucleotide Identity, DNA-DNA Hybridization and Amino Acid Identity values between strains (MEB004 and MEB108) and A. amylolytica DSM 18337 were (82.3 and 85.5), (25.0 and 29.2) and (86.7 and 90.2%). Both novel strains produced industrially important enzymes, such as amylase, lipase, cellulase, caseinase, and chitinase at pH 10 evidenced by the genomic presence of carbohydrate-active enzymes encoding genes. Genomic analyses further identified pH tolerance genes, affirming their adaptation to alkaline Lonar Lake. Dominant fatty acids were Summed feature 8 (C ω7c and/or C ω6c), C Summed feature 3, Sum In Feature 2 and C 3OH. The prevalent polar lipids included phosphatidyl ethanolamine, phosphatidyl glycerol, and diphosphatidyl glycerol. The major respiratory quinone was ubiquinone-8. Based on the polyphasic data, we propose the classification of strains MEB004 and MEB108 as novel species within the genus Alkalimonas assigning the names Alkalimonas mucilaginosa sp. nov. and Alkalimonas cellulosilytica sp. nov., respectively. The type strains are MEB004 (= MCC 5208 = JCM 35954 = NCIMB 15460) and MEB108 (= MCC 5330 = JCM 35955 = NCIMB 15461).
Topics: Lakes; India; Phylogeny; RNA, Ribosomal, 16S; Base Composition; DNA, Bacterial; Fatty Acids; Bacterial Typing Techniques; Genome, Bacterial; Water Microbiology; Hydrogen-Ion Concentration; Sequence Analysis, DNA; Nucleic Acid Hybridization
PubMed: 38850314
DOI: 10.1007/s10482-024-01986-6 -
China CDC Weekly May 2024Coxsackievirus A6 (CVA6) has emerged as a significant pathogen responsible for severe cases of hand, foot, and mouth disease (HFMD). This study aims to delineate the...
INTRODUCTION
Coxsackievirus A6 (CVA6) has emerged as a significant pathogen responsible for severe cases of hand, foot, and mouth disease (HFMD). This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6, thereby assisting in its surveillance and management.
METHODS
In this investigation, 74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and 2023. The gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST, DnaSP6, and PopART.
RESULTS
A significant portion (94.4%) of severe CVA6-associated HFMD cases (51 out of 54, with 20 lacking age information) were children under 5 years old. Among the 74 CVA6 strains analyzed, 72 belonged to the D3a sub-genotype, while only two strains were D2 sub-genotype. The average genetic distance between sequences prior to 2015 was 0.027, which increased to 0.051 when compared to sequences post-2015. Historical population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2012-2013, 2013-2014, and 2019-2020, resulting in the formation of 65 distinct haplotypes. Consistent with the MCC tree findings, transitioning between regional haplotypes required multiple base substitutions, showcasing an increase in population diversity during the evolutionary process (from 14 haplotypes in 2013 to 55 haplotypes over the subsequent decade).
CONCLUSIONS
CVA6, associated with severe HFMD, is evolving and presents a risk of outbreak occurrence. Thus, enhanced surveillance of severe HFMD is imperative.
PubMed: 38846357
DOI: 10.46234/ccdcw2024.086 -
BioRxiv : the Preprint Server For... May 2024Polyomaviruses are small, circular dsDNA viruses that can cause cancer. Alternative splicing of polyomavirus early transcripts generates large and small tumor antigens...
Polyomaviruses are small, circular dsDNA viruses that can cause cancer. Alternative splicing of polyomavirus early transcripts generates large and small tumor antigens (LT, ST) that play essential roles in viral replication and tumorigenesis. Some polyomaviruses also express middle tumor antigens (MTs) or Alternate LT ORFs (ALTOs), which are evolutionarily related but have distinct gene structures. MTs are a splice variant of the early transcript whereas ALTOs are overprinted on the second exon of the LT transcript in an alternate reading frame and are translated via an alternative start codon. Merkel cell polyomavirus (MCPyV), the only human polyomavirus that causes cancer, encodes an ALTO but its role in the viral lifecycle and tumorigenesis has remained elusive. Here, we show MCPyV ALTO acts as a tumor suppressor and is silenced in Merkel cell carcinoma (MCC). Rescuing ALTO in MCC cells induces growth arrest and activates NF-κB signaling. ALTO activates NF-κB by binding SQSTM1 and TRAF2&3 via two N-Terminal Activating Regions (NTAR1+2), resembling Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1).. Following activation, NF-κB dimers bind the MCPyV non-coding control region (NCCR) and downregulate early transcription. Beyond MCPyV, NTAR motifs are conserved in other polyomavirus ALTOs, which activate NF-κB signaling, but are lacking in MTs that do not. Furthermore, polyomavirus ALTOs downregulate their respective viral early transcription in an NF-κB and NTAR dependent manner. Our findings suggest that ALTOs evolved to suppress viral replication and promote viral latency and that MCPyV ALTO must be silenced for MCC to develop.
PubMed: 38826197
DOI: 10.1101/2024.05.24.595774 -
Neurological Research May 2024Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory...
BACKGROUND
Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity.
METHODS
Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (), calmodulin-dependent protein kinase (), N-methyl-D-aspartate receptors (), and cAMP-response element-binding protein () by western blotting and reverse transcription-polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1.
RESULTS
Post-natal exercise improved spatial memory ( < 0.05) and glucose levels ( < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression ( 40%, 62%, 43%, 66%), diabetic rats, by study end, showed increased protein/gene expression ( < 0.05) in emerging adulthood for both training groups.
CONCLUSION
Early-life exercise influenced hippocampal pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level.
PubMed: 38808654
DOI: 10.1080/01616412.2024.2359265 -
FEBS Open Bio May 2024Hypopharyngeal cancer gene regulatory networks and therapeutic molecules are a disease that is associated with EGFR-mutated lung adenocarcinoma. Here we utilized a...
Hypopharyngeal cancer gene regulatory networks and therapeutic molecules are a disease that is associated with EGFR-mutated lung adenocarcinoma. Here we utilized a bioinformatics approach to identify genetic commonalities between these two diseases. To this end, we examined microarray datasets from GEO (Gene Expression Omnibus) to identify differentially expressed genes, common genes, and hub genes between the selected two diseases. Our analyses identified potential therapeutic molecules for the selected diseases based on 10 hub genes with the highest interactions according to the degree topology method and the maximum clique centrality (MCC). These therapeutic molecules may have the potential for simultaneous treatment of these diseases.
PubMed: 38783639
DOI: 10.1002/2211-5463.13807 -
BMC Medical Genomics May 2024The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in...
BACKGROUND
The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS.
METHODS
This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed.
RESULTS
A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples.
CONCLUSION
NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.
Topics: Humans; Asthma; Child; Biomarkers; Mitochondria; Protein Interaction Maps; Gene Regulatory Networks; Gene Expression Profiling; MicroRNAs; Transcription Factors; Mitochondrial Proteins; RNA, Messenger
PubMed: 38783263
DOI: 10.1186/s12920-024-01901-y