Common Gene Research Articles

Identification of novel hub genes and immune infiltration in atopic dermatitis using integrated bioinformatics analysis

The aim of this study was to identify key genes and investigate the immunological mechanisms of atopic dermatitis (AD) at the molecular level via bioinformatics analysis. Gene expression profiles (GSE32924, GSE107361, GSE121212, and GSE230200) were obtained for screening common differentially expressed genes (co-DEGs) from the gene expression omnibus database. Functional enrichment analysis, protein–protein interaction network and module construction, and identification of common hub genes were performed. Hub genes were validated using receiver operating characteristic curve analysis based on GSE130588 and GSE16161. NetworkAnalyst was used to detect microRNAs (miRNAs) and transcription factors (TFs) associated with the hub genes. The immune cell infiltration was analyzed using the CIBERSORT algorithm to further analyze the correlation between hub genes and immune cells. A total of 146 co-DEGs were obtained, showing significant enrichment in cytokine–cytokine receptor interaction and JAK-STAT signaling pathway. Seven hub genes were identified by Cytoscape and validated with external datasets. Subsequent prediction of miRNAs and TFs targeting these hub genes revealed their regulatory roles. Analysis of immune cell infiltration and correlation revealed a significant positive correlation between CCL22 expression and the number of dendritic cells activated. The identified hub genes represent potential diagnostic and therapeutic targets in the immunological pathogenesis of AD.

The mitochondrial genome of Lavandula angustifolia Mill. (Lamiaceae) sheds light on its genome structure and gene transfer between organelles

BackgroundLavandula angustifolia holds importance as an aromatic plant with extensive applications spanning the fragrance, perfume, cosmetics, aromatherapy, and spa sectors. Beyond its aesthetic and sensory applications, this plant offers medicinal benefits as a natural herbal remedy and finds use in household cleaning products. While extensive genomic data, inclusive of plastid and nuclear genomes, are available for this species, researchers have yet to characterize its mitochondrial genome. This gap in knowledge hampers deeper understanding of the genome organization and its evolutionary significance.ResultsThrough the course of this study, we successfully assembled and annotated the mitochondrial genome of L. angustifolia, marking a first in this domain. This assembled genome encompasses 61 genes, which comprise 34 protein-coding genes, 24 transfer RNA genes, and three ribosomal RNA genes. We identified a chloroplast sequence insertion into the mitogenome, which spans a length of 10,645 bp, accounting for 2.94% of the mitogenome size. Within these inserted sequences, there are seven intact tRNA genes (trnH-GUG, trnW-CCA, trnD-GUC, trnS-GGA, trnN-GUU, trnT-GGU, trnP-UGG) and four complete protein-coding genes (psbA, rps15, petL, petG) of chloroplast derivation. Additional discoveries include 88 microsatellites, 15 tandem repeats, 74 palindromic repeats, and 87 forward long repeats. An RNA editing analysis highlighted an elevated count of editing sites in the cytochrome c oxidase genes, notably ccmB with 34 editing sites, ccmFN with 32, and ccmC with 29. All protein-coding genes showed evidence of cytidine-to-uracil conversion. A phylogenetic analysis, utilizing common protein-coding genes from 23 Lamiales species, yielded a tree with consistent topology, supported by high confidence values.ConclusionsAnalysis of the current mitogenome resource revealed its typical circular genome structure. Notably, sequences originally from the chloroplast genome were found within the mitogenome, pointing to the occurrence of horizontal gene transfer between organelles. This assembled mitogenome stands as a valuable resource for subsequent studies on mitogenome structures, their evolution, and molecular biology.

Network pharmacology-based strategy to reveal the mechanism of pinocembrin against ovarian cancer.

Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin's potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein-protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin's involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin's potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin's potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.

Prevalence, Characterization, and Epidemiological Relationships between ESBL and Carbapenemase-Producing Escherichia coli, Klebsiella pneumoniae, and Acinetobacter spp. Isolated from Humans and the Kitchen Environment of Two Greek Hospitals.

Extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing Enterobacterales and Acinetobacter spp. pose significant challenges as nosocomial pathogens, demonstrating resistance against various antimicrobials. Their presence in food suggests that hospital kitchens could serve as antibiotic resistance reservoirs leading to patients' infection. The aim of this study was to assess the prevalence and characteristics of β-lactam-resistant strains of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter spp. isolated from the kitchen environment and from the staff of two Greek hospitals. Strains were recovered after selective isolation with β-lactams and were identified with MALDI-TOF MS. Antimicrobial susceptibility and presence of common β-lactamase genes were evaluated. Protein profiles were examined to analyze potential relationships of the strain with those from hospital patients. E. coli strains were further categorized into phylogenetic groups. The overall prevalence in the kitchen environment was 4.5%, 1.5%, and 15.0% for E. coli, K. pneumoniae, and Acinetobacter spp., respectively, whereas the prevalence of Acinetobacter spp. in human skin was 4.0%. Almost all strains were multidrug-resistant. All E. coli strains were ESBL producers and belonged to phylogroups A and B1. All K. pneumoniae and seven Acinetobacter strains were carbapenemase-producers. A protein profile analysis showed relatedness between chicken and kitchen environment strains, as well as between kitchen environment and patient strains originated either from the same or from different hospitals. The results suggest that hospital kitchens may act as important pathogen hotspots contributing to the circulation of resistant strains in the hospital environment.

The gut microbiota of wild birds undergoing rehabilitation as a reservoir of multidrug-resistant enterococci in a metropolitan area in Brazil.

Enterococci are ubiquitous usually commensal bacteria that can act as opportunistic pathogens frequently associated with resistance to multiple antimicrobial classes. A variety of animals may carry potentially harmful enterococci. In the present work, the occurrence and characteristics of enterococci recovered from the fecal microbiota of wild birds belonging to four families (Accipitridae, Cathartidae, Falconidae and Strigidae) were investigated. Enterococci were recovered from 104 (92.0%) fecal samples obtained from 113 birds, and 260 strains were selected for additional characterization. Enterococcus faecalis was the predominant species (63.8%), followed by Enterococcus hirae (16.2%), Enterococcus faecium (11.5%), Enterococcus gallinarum (5.4%), Enterococcus avium (1.5%), Enterococcus casseliflavus (0.8%), and Enterococcus raffinosus and Enterococcus cecorum (0.4% each). Major percentages (11.9% 75.0%) of nonsusceptibility were observed to quinolones (particularly to enrofloxacin), erythromycin, rifampin, nitrofurantoin, tetracycline and streptomycin. Gentamicin and ampicillin resistances (13.3% each) were only detected among E. faecium. A total of 133 (51.2%) strains were MDR, showing a large variety of MDR profiles, composed by simultaneous resistance encompassing 3 to 12 antimicrobials. MDR strains were found in 68.2% of the birds. Antimicrobial resistance was associated with the presence of the aac(6')-aph(2″)-Ia, aph(2″)-Id, ant(6)-Ia, ant(9)-Ia, ant(9)-Ib, tet(M), tet(L), tet(S), erm(B), mef(A/E), msrC, and vat(D) genes. The most common virulence genes were efaA, gelE, ace, eeP, and asa1. PFGE analysis revealed a large genetic diversity among most of the strains. MLST performed for 35 E.faecalis strains revealed 23 different STs, whereas 14 STs were found among 18 E.faecium strains. Hospital-associated lineages ST22, ST25, ST56, ST1274 were identified. The results show that the wild birds investigated can carry a diversity of potentially hazardous enterococcal strains displaying multiple antimicrobial resistance and virulence genes, reinforcing the assumption that these animals provide an important target to monitor the circulation of microorganisms that deserve consideration under the One Health perspective.

Prevalence of bacteremia and antimicrobial resistance pattern among patients in South Lebanon

Bacteremia is a leading cause of morbidity and mortality worldwide. Rising prevalence and antimicrobial resistance (AMR) are critical public health issues. This study aims to determine the prevalence of bacteremia and the AMR pattern among patients in South Lebanon. A cross-sectional study analyzed 76 positive blood cultures from Hammoud and Labib Hospitals in South Lebanon between September 2023 and March 2024. The phenotype and antimicrobial susceptibility of gram-positive and gram-negative were determined by using disk diffusion. Genotypically, polymerase chain reaction was used to detect the carbapenemase-resistant Enterobacterales (CRE), extended-spectrum β-lactamases (ESBL), and methicillin-resistant Staphylococcus aureus genes. Out of 76 isolates, 38 (50%) were gram-positive and 38 (50%) were gram-negative. Escherichia coli was the most common among gram-negative (18. 42%), with 10.52% ESBL and 3.94% CRE. Staphylococcus coagulase negative was the most common among gram-positive (40.78%), followed by Staphylococcus aureus (6.57%), with 3.94% methicillin-resistant S. aureus. The prevalent ESBL gene was CTX-M (100%), and for the CRE, NDM (66.66%) was the most common gene. Regarding S. aureus, 66.66% were mecA. The diverse bacteremia isolates and resistance genes in South Lebanon reflect global variability in incidence and resistance profiles. High rates of bacteremia and AMR in South Lebanon underscore the need for effective antibiotic stewardship programs.

Predicting the Mechanism of Tiannanxing-shengjiang Drug Pair in Treating Pain Using Network Pharmacology and Molecular Docking Technology.

This study aimed to analyze the potential targets and mechanism of the Tiannanxing-shengjiang drug pair in pain treatment using network pharmacology and molecular docking technology. The active components and target proteins of Tiannanxing-Shengjiang were obtained from the TCMSP database. The pain-related genes were acquired from the DisGeNET database. The common target genes between Tiannanxing-Shengjiang and pain were identified and subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses on the DAVID website. AutoDockTools and molecular dynamics simulation analysis were used to assess the binding of the components with the target proteins. Ten active components were screened out, such as stigmasterol, β-sitosterol, and dihydrocapsaicin. A total of 63 common targets between the drug and pain were identified. GO analysis showed the targets to be mainly associated with biological processes, such as inflammatory response and forward regulation of the EKR1 and EKR2 cascade. KEGG analysis revealed 53 enriched pathways, including pain-related calcium signaling, cholinergic synaptic signaling, and serotonergic pathway. Five compounds and 7 target proteins showed good binding affinities. These data suggest that Tiannanxing-shengjiang may alleviate pain through specific targets and signaling pathways. The active ingredients in Tiannanxing-shengjiang might alleviate pain by regulating genes, such as CNR1, ESR1, MAPK3, CYP3A4, JUN, and HDAC1 through the signaling pathways, including intracellular calcium ion conduction, cholinergic prominent signaling, and cancer signaling pathway.

Pathogenesis and potential diagnostic biomarkers of atrial fibrillation in Chinese population: a study based on bioinfor-matics

To explore the pathogenesis and potential biomarkers of atrial fibrillation based on bioinformatics. Differentially expressed genes and module genes related to atrial fibrillation were obtained from GSE41177 and GSE79768 datasets (Chinese-origin tissue samples) through differential expression analysis and weighted gene co-expression network analysis. Candidate hub genes were obtained by taking intersections, and hub genes were obtained after gender stratification. Subsequently, functional enrichment analysis and immune infiltration analysis were performed. Four machine learning models were constructed based on the hub genes, and the optimal model was selected to construct a prediction nomogram. The prediction ability of the nomogram was verified using calibration curves and decision curves. Finally, potential therapeutic drugs for atrial fibrillation were screened from the DGIdb database. A total of 67 differentially expressed genes and 65 module genes related to atrial fibrillation were identified. Functional enrichment analysis indicated that the pathogenesis of atrial fibrillation was closely related to inflammatory response, immune response, and immune and infectious diseases. Four common hub genes (TYROBP, FCER1G, EVI2B and SOD2), and two genes specifically expressed in male (PILRA and SLC35G3) and female (HLA-DRA and GATP) patients with atrial fibrillation were obtained after gender-segregated screening. The extreme gradient boosting model had satisfactory diagnostic efficiency, and the nomogram constructed based on the hub genes, male significant variables (PILRA, SLC35G3 and SOD2), and female significant variables (FCER1G, SOD2 and TYROBP) had satisfactory predictive ability. Immune infiltration analysis demonstrated a disturbed immune infiltration microenvironment in atrial fibrillation with a higher abundance of plasma cells, neutrophils, and γδT cells, with a higher abundance of neutrophils in males and resting mast cells in females. Two potential drugs for the treatment of atrial fibrillation, valproic acid and methotrexate, were obtained by database and literature screening. The pathogenesis of atrial fibrillation is closely related to inflammation and immune response, and the microenvironment of immune cell infiltration of cardiomyocytes in the atrial tissue of patients with atrial fibrillation is disordered. TYROBP, FCER1G, EVI2B and SOD2 serve as potential diagnostic biomarkers of atrial fibrillation; PILRA and SLC35G3 serve as potential specific diagnostic biomarkers of atrial fibrillation in the male population, which can effectively predict the risk of atrial fibrillation development and are also potential targets for the treatment of atrial fibrillation.

P4.07F.03 A Cost-Effective Tumor-Informed ctDNA Analysis for MRD Detection in Resected NSCLC With Common Driver Genes

P4.07F.03 A Cost-Effective Tumor-Informed ctDNA Analysis for MRD Detection in Resected NSCLC With Common Driver Genes

Detection of Alport gene variants in children and young people with persistent haematuria.

Genetic kidney disease is an important cause of persistent microscopic haematuria in children and young people. We aimed to determine the frequency of variants in the Alport syndrome genes (COL4A3, COL4A4 or COL4A5) in individuals under 18 years of age presenting with persistent microscopic haematuria to a single specialist centre in the UK over a 10-year period. We conducted a retrospective longitudinal study of individuals referred to a tertiary paediatric nephrology service with persistent microscopic haematuria between April 2012 to 2022. A total of 224 individuals (female 51.8%) were evaluated with persistent microscopic haematuria of greater than 6 months duration. The age at presentation was 7.5 ± 4.3 years (mean ± SD) with a duration of follow-up of 6.8 ± 4.6 years (mean ± SD). Targeted exome sequencing was performed in 134 individuals and 91 (68%) had a pathogenic or likely pathogenic variant in COL4A3, COL4A4 or COL4A5. Only 49.5% of individuals with identified variants had a family history of microscopic haematuria documented and 37.4% (34/91) had additional proteinuria at presentation. COL4A5 was the most common gene affected and missense variants affecting glycine residues were the most common variant type. Over two-thirds of children and young people who underwent genetic testing had an identifiable genetic basis for their microscopic haematuria and over half did not have a documented family history. Genetic testing should be part of the evaluation of persistent microscopic haematuria despite a negative family history.

Identification of diagnostic candidate genes in COVID-19 patients with sepsis.

Coronavirus Disease 2019 (COVID-19) and sepsis are closely related. This study aims to identify pivotal diagnostic candidate genes in COVID-19 patients with sepsis. We obtained a COVID-19 data set and a sepsis data set from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) and module genes using the Linear Models for Microarray Data (LIMMA) and weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, protein-protein interaction (PPI) network construction, and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression and Random Forest (RF)) were used to identify candidate hub genes for the diagnosis of COVID-19 patients with sepsis. Receiver operating characteristic (ROC) curves were developed to assess the diagnostic value. Finally, the data set GSE28750 was used to verify the core genes and analyze the immune infiltration. The COVID-19 data set contained 3,438 DEGs， and 595 common genes were screened in sepsis. sepsis DEGs were mainly enriched in immune regulation. The intersection of DEGs for COVID-19 and core genes for sepsis was 329, which were also mainly enriched in the immune system. After developing the PPI network, 17 node genes were filtered and thirteen candidate hub genes were selected for diagnostic value evaluation using machine learning. All thirteen candidate hub genes have diagnostic value, and 8 genes with an Area Under the Curve (AUC) greater than 0.9 were selected as diagnostic genes. Five core genes (CD3D, IL2RB, KLRC, CD5, and HLA-DQA1) associated with immune infiltration were identified to evaluate their diagnostic utility COVID-19 patients with sepsis. This finding contributes to the identification of potential peripheral blood diagnostic candidate genes for COVID-19 patients with sepsis.

Unveiling Insights into the Whole Genome Sequencing of Mycobacterium spp. Isolated from Siamese Fighting Fish (Betta splendens)

This study aims to genomically elucidate six isolates of rapidly growing non-tuberculous mycobacteria (RGM) derived from Siamese fighting fish (Betta splendens). These isolates had previously undergone phenotypic and biochemical characterization, antibiotic susceptibility testing, and in vivo virulence assessment. Initial DNA barcoding using the 16S rRNA sequence assigned these six isolates to five different species, namely Mycobacterium chelonae (BN1983), M. cosmeticum (BN1984 and N041), M. farcinogenes (SNSK5), M. mucogenicum (BN1956), and M. senegalense (BN1985). However, the identification relied solely on the highest percent identity of the 16S rRNA gene, raising concerns about the taxonomic ambiguity of these species. Comprehensive whole genome sequencing (WGS) and extended genomic comparisons using multilocus sequence typing (MLST), average nucleotide identity (ANI), and digital DNA–DNA hybridization (dDDH) led to the reclassification of BN1985 and SNSK5 as M. conceptionense while confirming BN1983 as M. chelonae and BN1984 and N041 as M. cosmeticum. Notably, the analysis of the BN1956 isolate revealed a potential new species that is proposed here as M. mucogenicum subsp. phocaicum sp. nov. Common genes encoding “mycobacterial” virulence proteins, such as PE and PPE family proteins, MCE, and YrbE proteins, were detected in all six isolates. Two species, namely M. chelonae and M. cosmeticum, appear to have horizontally acquired T6SS-II (clpB), catalase (katA), GroEL (groel), and capsule (rmlb) from distantly related environmental bacteria such as Klebsiella sp., Neisseria sp., Clostridium sp., and Streptococcus sp. This study provides the first draft genome sequence of RGM isolates currently circulating in B. splendens and underscores the necessity of WGS for the identification and classification of mycobacterial species.

Differential Effect of Aldosterone or Mineralocorticoid Receptor Overexpression on Retinal Inflammation.

Overactivation of the mineralocorticoid receptor (MR) pathway is proinflammatory and contributes to the pathogenesis of diabetic retinopathy and of age-related macular degeneration. Excess of aldosterone, the specific MR ligand, is known to stimulate the production of proinflammatory cytokines and chemokines in extrarenal tissues and cells. In the RPE/choroid complex, aldosterone upregulated genes encoding proteins of the inflammatory response and downregulated genes encoding proteins involved in synaptic activity and neurotransmitters. Yet, cortisol, which is the main MR ligand in the eye, is a potent anti-inflammatory endogenous glucocorticoid. The aim of the present work was to better understand the role of MR activation in retinal inflammation either by acute injection of aldosterone or overexpression of the receptor. We first analyzed the retinal transcriptomic regulation induced by acute intraocular injection of aldosterone in the rat. Then, we used a transgenic rat overexpressing human MR (hMR) to also conduct retinal transcriptomic analysis as well as histological evaluation of the retina, retinal pigment epithelium and choroid. Our results show that acute intravitreal injection of aldosterone is highly proinflammatory, upregulating pathways related to microglial activation, oxidative stress, cell death, and downregulating pathways related to glial/neuronal cells activity and proper neurotransmission. On the other hand, hMR overexpression mediates a low-grade inflammation in the retina, associated with notable choroidal inflammation and choroidal neuropathy. Consequences of hMR overexpression or aldosterone-injection on retinal transcriptome reveal very distinct pathological mechanisms, with only a few common genes regulated, most of them not being regulated in the same way. Although aldosterone is highly proinflammatory in the retina, MR overactivation in its physiologic milieu mediates a low-grade inflammation in the neural retina.

Influence of budesonide and fluticasone propionate in the anti-osteoporotic potential in human bone marrow-derived mesenchymal stem cells via stimulation of osteogenic differentiation

Osteoporosis is a prevalent bone condition with adverse effects observed in patients undergoing long-term glucocorticoid therapy, resulting in bone demineralization and tissue loss. There has been limited studies on the global response to dexamethasone in terms of comparing its expression profile to other common glucocorticoids during osteogenic differentiation. This study focused on the downregulated gene expression profile of glucocorticoid compounds; dexamethasone, budesonide, and fluticasone propionate, during osteogenic differentiation to elucidate the related target genes and pathways associated with the anti-osteoporotic potential of telomerase-immortalized human bone marrow-derived mesenchymal stem cells using a bioinformatics approach. Based on gene expression microarrays experiments and bioinformatics analysis, several key genes involved in the regulation of osteogenic differentiation and osteoporosis development in mesenchymal stem cells that were targeted by these specific glucocorticoids were determined. Network analysis using GeneCards, OMIM, and CTD databases were performed and osteoporosis-related genes were identified. LIMMA and moderated Welch test R packages were performed to determine significant downregulated differentially expressed genes for each glucocorticoid treatment. A total of 479 (dexamethasone), 84 (budesonide), and 889 (fluticasone propionate) differentially expressed genes were identified for each glucocorticoid, of which 35 common genes overlapped. Enrichment pathway analysis was conducted using Metascape, and protein-protein interaction networks were constructed using the STRING database and Cytoscape software to determine potential target genes involved with osteoporosis. Enrichment pathway analysis revealed genes involved in 3 Reactome pathways namely cytokine signaling in immune system, immune system and the interferon alpha/beta signaling pathways and identified 10 hub genes based on the PPI network to determine potential target pathways associated with osteoporosis. These findings provide preliminary insights into the relationship between the key target genes of dexamethasone, budesonide, and fluticasone propionate, and the pathways associated with regulated osteoporosis metabolism during osteogenic differentiation.

Exploration of the shared gene signatures and comorbidity mechanisms of primary aldosteronism and atrial fibrillation.

Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant, and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF. Datasets were obtained from the Gene Expression Omnibus (GEO) database. Hub genes were identified by enrichment and protein‒protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 and GSE41177. Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples. The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF. Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.

Identification and molecular modelling of potential drugs targeting the genes involved in the progression of lung cancer in patients with idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is characterized by progressive fibrosis in the lung parenchyma. Given the fact that IPF patients are at significant risk of developing lung cancer (LC), the overlapping gene signatures between IPF and LC need to be explored. MethodsTwo datasets (GSE79544 and GSE103888) were procured from the Gene Expression Omnibus repository and used to determine the overlapping genes between IPF and LC. Next, the prediction ability of these genes in differentiating the diseased group from controls was explored using two machine learning (ML) models (random forest and k-nearest neighbor). Potential drugs targeting the candidate genes were identified, and advanced structural analysis was conducted to determine the binding affinity between the candidate drug and target receptor. ResultA total of ten common genes (CCL13, CXCL2, MALT1, MARCKS, PLA2G7, SEMA6B, SFTPB, SPARC, SPP1, and TLCD2) are differentially expressed in IPF and LC as compared to the controls. PLA2G7 demonstrated promising potential in differentiating between IPF, LC, and controls. The increased expression correlated with poor survival in patients with LC. The expression of PLA2G7 indicated a similar trend in the validation dataset. Darapladib, a selective inhibitor that belongs to toxicity class 4 and lethal dose50 value of 800 mg/kg exhibited maximum potential in targeting PLA2G7 with a binding affinity score of −9.2 kcal/mol (chain A) and −9.3 kcal/mol (chain B), respectively. ConclusionThe present study is the first of its kind that combines in-silico and ML algorithms to identify the gene signatures and promising drugs for treating the progression of LC in patients with IPF.

A genome-wide gene-environmental interaction study identified novel loci for the relationship between ambient air pollution exposure and depression, anxiety

BackgroundGenetic factors and environmental exposures, including air pollution, contribute to the risk of depression and anxiety. While the association between air pollution and depression and anxiety has been established in the UK Biobank, there has been limited research exploring this relationship from a genetic perspective. MethodsBased on individual genotypic and phenotypic data from a cohort of 104,385 participants in the UK Biobank, a polygenic risk score for depression and anxiety was constructed to explore the joint effects of nitric oxide (NO), nitrogen dioxide (NO2), particulate matter (PM) with a diameter of ⩽2.5 μm (PM2.5) and 2.5–10 μm (PMcoarse) with depression and anxiety by linear and logistic regression models. Subsequently, a genome-wide gene-environmental interaction study (GWEIS) was performed using PLINK 2.0 to identify the genes interacting with air pollution for depression and anxiety. ResultsA substantial risk of depression and anxiety development was detected in participants exposed to the high air pollution concomitantly with high genetic risk. GWEIS identified 166, 23, 18, and 164 significant candidate loci interacting with NO, NO2, PM2.5, and PMcoarse for Patient Health Questionnaire-9 (PHQ-9) score, and detected 44, 10, 10, and 114 candidate loci associated with NO, NO2, PM2.5, and PMcoarse for General Anxiety Disorder (GAD-7) score, respectively. And some significant genes overlapped among four air pollutants, like TSN (rs184699498, PNO2 = 3.47 × 10−9; rs139212326, PPM2.5 = 1.51 × 10−8) and HSP90AB7P(rs150987455, PNO2 = 1.63 × 10−11; rs150987455, PPM2.5 = 7.64 × 10−11), which were common genes affecting PHQ-9 score for both NO2 and PM2.5. ConclusionOur study identified the joint effects of air pollution with genetic susceptibility on the risk of depression and anxiety, and provided several novel candidate genes for the interaction, contributing to an understanding of the genetic architecture of depression and anxiety.

Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.

Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking. We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD. We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD. We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.

Divergent Heat Stress Responses in Bactrocera tryoni and Ceratitis capitata.

Invasive Tephritid fruit flies rank among the most destructive agricultural and horticultural pests worldwide. Heat treatment is commonly employed as a post-harvest method to exterminate fruit flies in fruits or vegetables. These pest species exhibit distinct tolerance to heat treatments, suggesting that the molecular pathways affected by heat may differ among species. In this study, the Queensland fruit fly (Qfly), Bactrocera tryoni, was utilised as a model investigate its molecular response to heat stress through heat bioassays. RNA samples from flies before and after heat treatment were extracted and sequenced to identify genes with significant changes in expression. These findings were compared to another serious Tephritid fruit fly species, the Mediterranean fruit fly (Medfly), Ceratitis capitata, under similar heat treatment conditions. The analysis reveals only three common genes: heat shock protein 70 (HSP70), HSP68, and 14-3-3 zeta protein. However, despite these shared genes, their expression patterns differ between Qfly and Medfly. This suggests that these genes might play different roles in the heat responses of each species and could be regulated differently. This study presents the first evidence of differing molecular responses to heat between Qfly and Medfly, potentially linked to their varied origins, habitats, and genetic backgrounds. These findings offer new insights into Tephritid fruit fly responses to heat at the molecular level, which may help refine post-harvest strategies to control these pests in the future.

Identification and phylogenetic analysis of carbapenemase genes from clinical strains of Klebsiella pneumoniae.

Klebsiella pneumoniae is an encapsulated Gram-negative bacterium that is responsible for numerous infections in healthcare facilities worldwide and is frequently isolated. The World Health Organization has listed K. pneumoniaeas as a critical antibiotic resistant bacterial pathogen for which new antibiotics are urgently needed. This study aimed to use molecular tools to identify and examine antibiotic resistance in clinical strains of K. pneumoniae. A total of 15 unduplicated K. pneumoniae strains isolated from patient samples with multidrug-resistant (MDR) profiles were subjected to polymerase chain reaction (PCR) to amplify the most common carbapenem resistance genes. (GTG)5 PCR and phylogenetic analysis were performed to identify the genetic relationship between the strains. All strains yielded a (GTG)5-PCR profile, and this allowed us to group these strains into 8 groups according to the size and number of characteristic bands. Phylogenetic analysis was done using the free software UPGMA and a single bacterial clone with a correlation coefficient of over 97% was identified. New Delhi metallo-beta-lactamase NDM-like (blaNDM) carbapenem resistance genes were detected in three strains of K. pneumoniae, which represented a resistance rate of 20%. However, carbapenemases type A [Klebsiella pneumoniae carbapenemase (KPC) and imipenem-hydrolysing beta-lactamase (IMI), type D [oxacillinase-48 (OXA-48)], and other metallo-β-lactamase [Verona integron-encoded metallo-beta-lactamase (VIM), and enzyme active on imipenem (IMP)] were not detected. We identified and grouped the blaNDM resistance genes of Klebsiella pneumonia strains.