Enriched Gene Ontology Terms Research Articles

TICRR as a potential prognostic biomarker for lung adenocarcinoma: A comprehensive analysis using TCGA database.

To investigate the role of TopBP1-interacting checkpoint and replication regulator (TICRR) in the tumorigenesis and prognosis of lung adenocarcinoma (LUAD) patients. Wilcoxon signed-rank test and logistic regression were utilized to analyze the relationship between clinical characteristics and TICRR expression in LUAD from TCGA dataset. Kaplan-Meier plots and Cox regressions were used to assess the impact of TICRR impact on prognosis. ROC curves and nomograms were generated to further evaluate the relationship between TICRR expression and the risk of LUAD. Gene set enrichment analysis (GSEA) was conducted on TCGA dataset, and ssGSEA was employed to investigate the association between TICRR and immune infiltrates. The results showed that high TICRR expression was significantly associated with various clinical factors including gender, age, pathological stage, T stage, N stage, M stage, outcome of primary therapy and smoking status. ROC curves also demonstrated that TICRR was a promising biomarker for molecular pathology diagnosis in LUAD patients (AUC = 0.952). Further analysis using gene ontology (GO) term enrichment and GSEA revealed an abnormal correlation between TICRR expression and cell division. Interestingly, ssGSEA analysis showed that TICRR expression correlated with multiple immune cell types, such as Th2 cell, TFH cell, mast cell, iDC, eosinophils, and dendritic cell. Lastly, the KM-plotters indicated that LUAD patients with high TICRR expression obtained worse life expectancy (P < .001). TICRR has proven to be a valuable tool in predicting disease progression and prognosis in patients with LUAD, thereby establishing itself as a fitting biomarker for forecasting overall survival (OS) of LUAD patients.

Sulforaphane enhanced muscle growth by promoting lipid oxidation through modulating key signaling pathways.

Sulforaphane (SFN) has shown diverse effects on human health and diseases. SFN was administered daily to C57BL/6J mice at doses of 1 mg/kg (SFN1) and 3 mg/kg (SFN3) for 8 weeks. Both doses of SFN accelerated body weight increment. The cross-sectional area and diameter of Longissimus dorsi (LD) muscle fibers were enlarged in SFN3 group. Triglyceride (TG) and total cholesterol (TC) levels in LD muscle were decreased in SFN groups. RNA sequencing results revealed that 2455 and 2318 differentially expressed genes (DEGs) were found in SFN1 and SFN3 groups, respectively. Based on GO enrichment analysis, 754 and 911 enriched GO terms in the SFN1 and SFN3 groups, respectively. KEGG enrichment analysis shown that one KEGG pathway was enriched in the SFN1 group, while six KEGG pathways were enriched in the SFN3 group. The expressions of nine selected DEGs validated with qRT-PCR were in line with the RNA sequencing data. Furthermore, SFN treatment influenced lipid and protein metabolism related pathways including AMPK signaling, fatty acid metabolism signaling, cholesterol metabolism signalling, PPAR signaling, peroxisome signaling, TGFβ signaling, and mTOR signaling. In summary, SFN elevated muscle fibers size and reduced TG and TC content of in LD muscle by modulating protein and lipid metabolism-related signaling pathways.

Transcriptome analysis of avian livers reveals different molecular changes to three urban pollutants: Soot, artificial light at night and noise

Identifying key molecular pathways and genes involved in the response to urban pollutants is an important step in furthering our understanding of the impact of urbanisation on wildlife. The expansion of urban habitats and the associated human-introduced environmental changes are considered a global threat to the health and persistence of humans and wildlife. The present study experimentally investigates how short-term exposure to three urban-related pollutants -soot, artificial light at night (ALAN) and traffic noise-affects transcriptome-wide gene expression in livers from captive female zebra finches (Taeniopygia guttata). Compared to unexposed controls, 17, 52, and 28 genes were differentially expressed in soot, ALAN and noise-exposed birds, respectively. In soot-exposed birds, the enriched gene ontology (GO) terms were associated with a suppressed immune system such as interferon regulating genes (IRGs) and responses to external stimuli. For ALAN-exposed birds, enriched GO terms were instead based on downregulated genes associated with detoxification, redox, hormonal-, and metabolic processes. Noise exposure resulted in downregulation of genes associated with the GO terms: cellular responses to substances, catabolic and cytokine responses. Among the individually differentially expressed genes (DEGs), soot led to an increased expression of genes related to tumour progression. Likewise, ALAN revealed an upregulation of multiple genes linked to different cancer types. Both sensory pollutants (ALAN and noise) led to increased expression of genes linked to neuronal function. Interestingly, noise caused upregulation of genes associated with serotonin regulation and function (SLC6A4 and HTR7), which previous studies have shown to be under selection in urban birds. These outcomes indicate that short-term exposure to the three urban pollutants perturbate the liver transcriptome, but most often in different ways, which highlights future studies of multiple-stress exposure and their interactive effects, along with their long-term impacts for urban-dwelling wildlife.

Integrated Analysis of Transcriptome Profiles and lncRNA-miRNA-mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne's Disease in Dairy Cattle.

Paratuberculosis or Johne's disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.

Single-cell RNA sequencing of human oocytes reveals a differential transcriptomic profile associated with agar-like zona pellucida

BackgroundAgar-like zona pellucida (ZP) is the most common type of abnormal ZP, and is one of the causes of low fertility or infertility. However, the molecular mechanism of agar-like ZP is unclear. Single-cell RNA-sequencing (scRNA-seq) analysis was used to assess the cellular and molecular landscape of oocytes with agar-like ZP.MethodsHuman metaphase I (MI) oocytes were collected from four patients with agar-like ZP and four healthy donors. Total RNA was isolated, cDNA was synthesized, and libraries were generated and subsequently sequenced on a HiSeq 2500 instrument. The scRNA-seq data were analyzed with R software.ResultsWe identified 1320 genes that were differentially expressed between agar-like ZP oocytes and healthy donor oocytes. Gene Ontology term enrichment results showed that the genes downregulated in agar-like ZP oocytes were significantly related to extracellular matrix organization, while the genes upregulated in agar-like ZP oocytes were significantly related to the regulation of response to DNA damage stimulus. The Kyoto Encyclopedia of Genes and Genomes enrichment results showed that genes were enriched in the ECM-receptor interaction pathway and focal adhesion pathway. Other signaling pathways important in oocyte development were also enriched, such as PI3K-Akt. Differential expression analysis identified UBC, TLR4, RELA, ANXA5, CAV1, KPNA2, CCNA2, ACTA2, FYN and ITGB3 as genetic markers of oocytes with agar-like ZP.ConclusionsOur findings suggest that agar-like ZP oocytes exhibit significant downregulation of genes involved in the ECM-receptor interaction signaling pathway and focal adhesion pathway, which could lead to aberrant ZP formation, while the upregulated genes were significantly related to regulation of the response to DNA damage stimulus. Agar-like ZP formation may interfere with the normal exchange of signals between oocytes and perivitelline granulosa cells, thereby preventing cumulus cells from participating in oocyte DNA damage repair and causing MI arrest.

Transcriptome Study in Sicilian Patients with Autism Spectrum Disorder.

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term "Response to Oxygen-Containing Compound". Additionally, the GO Cellular Component pathway "Mitochondrion" stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD.

Antibacterial activity and mechanism of the sesquiterpene δ-cadinene against Listeria monocytogenes

Listeria monocytogenes is a food-borne pathogen that seriously threatens human health. We analyzed the antibacterial activity and mechanism of δ-cadinene against L. monocytogenes. The effect of δ-cadinene on L. monocytogenes gene expression was investigated using RNA sequencing. δ-Cadinene inhibited L. monocytogenes growth at a minimum inhibitory concentration of 5 μL/mL and a minimum bactericidal concentration of 10 μL/mL. In addition, δ-cadinene suppressed biofilm formation, altered cell morphology, and damaged the cell membrane of L. monocytogenes, enhancing membrane permeability and affecting the membrane potential. Of note, "plasma membrane" and "membrane" were the most significantly enriched Gene Ontology terms. Sixteen differentially expressed genes were strongly correlated with biofilm formation, protein and nucleic acid leakage, and membrane potential. The growth of L. monocytogenes in milk was effectively controlled with 10 μL/mL δ-cadinene, especially at 4 °C. In conclusion, treatment with δ-cadinene could be a potential strategy for controlling the contamination of foods by L. monocytogenes.

Proteomic analysis reveals dynamic changes in cloacal fluid composition during the reproductive season in a sexually promiscuous passerine

Cryptic female choice (CFC) is a component of postcopulatory sexual selection that allows females to influence the fertilization success of sperm from different males. While its precise mechanisms remain unclear, they may involve the influence of the protein composition of the female reproductive fluids on sperm functionality. This study maps the protein composition of the cloacal fluid across different phases of female reproductive cycle in a sexually promiscuous passerine, the barn swallow. Similar to mammals, the protein composition in the female reproductive tract differed between receptive (when females copulate) and nonreceptive phases. With the change in the protein background, the enriched gene ontology terms also shifted. Within the receptive phase, distinctions were observed between proteomes sampled just before and during egg laying. However, three proteins exhibited increased abundance during the entire receptive phase compared to nonreceptive phases. These proteins are candidates in cryptic female choice, as all of them can influence the functionality of sperm or sperm-egg interaction. Our study demonstrates dynamic changes in the cloacal environment throughout the avian breeding cycle, emphasizing the importance of considering these fluctuations in studies of cryptic female choice.

GOAT: efficient and robust identification of gene set enrichment

Gene set enrichment analysis is foundational to the interpretation of high throughput biology. Identifying enriched Gene Ontology (GO) terms or disease-associated gene sets within a list of gene effect sizes that represent experimental outcomes is an everyday task in life science that crucially depends on robust and sensitive statistical tools. We here present GOAT, a parameter-free algorithm for gene set enrichment analysis of preranked gene lists. The algorithm can precompute null distributions from standardized gene scores, enabling enrichment testing of the GO database in one second. Validations using synthetic data show that estimated gene set p-values are well calibrated under the null hypothesis and invariant to gene list length and gene set size. Application to various real-world proteomics and gene expression studies demonstrates that GOAT identifies more significant GO terms as compared to current methods. GOAT is freely available as an R package and user-friendly online tool for gene set enrichment analyses that includes interactive data visualizations: https://ftwkoopmans.github.io/goat.

Integrated Transcriptome and Metabolome Analysis Reveals Molecular Mechanisms Underlying Resistance to Phytophthora Root Rot.

Soybean production is significantly impacted by Phytophthora root rot (PRR), which is caused by Phytophthora sojae. The nucleotide-binding leucine-rich repeat (NLR) gene family plays a crucial role in plant disease resistance. However, current understanding of the function of soybean NLR genes in resistance to PRR is limited. To address this knowledge gap, transgenic soybean plants overexpressing the NLR gene (Glyma.18g283200) were generated to elucidate the molecular mechanism of resistance. Here, transcript changes and metabolic differences were investigated at three time points (12, 24, and 36 h) after P. sojae infection in hypocotyls of two soybean lines, Dongnong 50 (susceptible line, WT) and Glyma.18g283200 overexpression line (resistant line, OE). Based on the changes in differentially expressed genes (DEGs) in response to P. sojae infection in different lines and at different time points, it was speculated that HOPZ-ACTIVATED RESISTANCE 1 (ZAR1), valine, leucine, and isoleucine degradation, and phytohormone signaling may be involved in the defense response of soybean to P. sojae at the transcriptome level by GO term and KEGG pathway enrichment analysis. Differentially accumulated metabolites (DAMs) analysis revealed that a total of 223 and 210 differential metabolites were identified in the positive ion (POS) and negative ion (NEG) modes, respectively. An integrated pathway-level analysis of transcriptomics (obtained by RNA-seq) and metabolomics data revealed that isoflavone biosynthesis was associated with disease resistance. This work provides valuable insights that can be used in breeding programs aiming to enhance soybean resistance against PRR.

Ecological transcriptomics reveals stress response pathways of a ground-herb species in a waterlogging gradient of Amazonian riparian forests.

Environmental stress is a fundamental facet of life and a significant driver of natural selection in the wild. Gene expression diversity may facilitate adaptation to environmental changes, without necessary genetic change, but its role in adaptive divergence remains largely understudied in Neotropical systems. In Amazonian riparian forests, species distribution is predominantly influenced by species' waterlogging tolerance. The flooding gradient delineates distinct wetland forest types, shaping habitats and species characteristics. Here we investigated the molecular basis of environmental stress response in a tropical ground-herb species (Ischnosiphon puberulus) to environmental variation in Amazonian riparian forests. We compared environmental variables and gene expression profiles from individuals collected in two forest types: Igapó and Terra firme in the Amazonian riparian forests. Predictable seasonal flooding poses a significant challenge in Igapó compared to Terra firme environments, with the former presenting higher water column height and longer flooding duration. Our findings suggest that contrasting environmental conditions related to flooding regimes are important drivers of population genetic differentiation and differential gene expression in I. puberulus. Enriched gene ontology terms highlight associations with environmental stresses, such as defence response, water transport, phosphorylation, root development, response to auxin, salicylic acid and oxidative stress. By uncovering key environmental stress response pathways conserved across populations, I. puberulus offers novel genetic insights into the molecular basis of plant reactions to environmental constraints found in flooded areas of this highly biodiverse neotropical ecosystem.

Effect of Bacterial Extracellular Polymeric Substances from Enterobacter spp. on Rice Growth under Abiotic Stress and Transcriptomic Analysis.

Plant biostimulants have received attention as sustainable alternatives to chemical fertilizers. Extracellular polymeric substances (EPSs), among the compounds secreted by plant growth-promoting rhizobacteria (PGPRs), are assumed to alleviate abiotic stress. This study aims to investigate the effect of purified EPSs on rice under abiotic stress and analyze their mechanisms. A pot experiment was conducted to elucidate the effects of inoculating EPSs purified from PGPRs that increase biofilm production in the presence of sugar on rice growth in heat-stress conditions. Since all EPSs showed improvement in SPAD after the stress, Enterobacter ludwigii, which was not characterized as showing higher PGP bioactivities such as phytohormone production, nitrogen fixation, and phosphorus solubilization, was selected for further analysis. RNA extracted from the embryos of germinating seeds at 24 h post-treatment with EPSs or water was used for transcriptome analysis. The RNA-seq analysis revealed 215 differentially expressed genes (DEGs) identified in rice seeds, including 139 up-regulated and 76 down-regulated genes. A gene ontology (GO) enrichment analysis showed that the enriched GO terms are mainly associated with the ROS scavenging processes, detoxification pathways, and response to oxidative stress. For example, the expression of the gene encoding OsAAO5, which is known to function in detoxifying oxidative stress, was two times increased by EPS treatment. Moreover, EPS application improved SPAD and dry weights of shoot and root by 90%, 14%, and 27%, respectively, under drought stress and increased SPAD by 59% under salt stress. It indicates that bacterial EPSs improved plant growth under abiotic stresses. Based on our results, we consider that EPSs purified from Enterobacter ludwigii can be used to develop biostimulants for rice.

Comparative transcriptome analysis reveals molecular damage associated with cryopreservation in Crassostrea angulata D-larvae rather than to cryoprotectant exposure

BackgroundThe Portuguese oyster Crassostrea angulata, a bivalve of significant economic and ecological importance, has faced a decline in both production and natural populations due to pathologies, climate change, and anthropogenic factors. To safeguard its genetic diversity and improve reproductive management, cryopreservation emerges as a valuable strategy. However, the cryopreservation methodologies lead to some damage in structures and functions of the cells and tissues that can affect post-thaw quality. Transcriptomics may help to understand the molecular consequences related to cryopreservation steps and therefore to identify different freezability biomarkers. This study investigates the molecular damage induced by cryopreservation in C. angulata D-larvae, focusing on two critical steps: exposure to cryoprotectant solution and the freezing/thawing process.ResultsExpression analysis revealed 3 differentially expressed genes between larvae exposed to cryoprotectant solution and fresh larvae and 611 differentially expressed genes in cryopreserved larvae against fresh larvae. The most significantly enriched gene ontology terms were “carbohydrate metabolic process”, “integral component of membrane” and “chitin binding” for biological processes, cellular components and molecular functions, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified the “neuroactive ligand receptor interaction”, “endocytosis” and “spliceosome” as the most enriched pathways. RNA sequencing results were validate by quantitative RT-PCR, once both techniques presented the same gene expression tendency and a group of 11 genes were considered important molecular biomarkers to be used in further studies for the evaluation of cryodamage.ConclusionsThe current work provided valuable insights into the molecular repercussions of cryopreservation on D-larvae of Crassostrea angulata, revealing that the freezing process had a more pronounced impact on larval quality compared to any potential cryoprotectant-induced toxicity. Additionally, was identify 11 genes serving as biomarkers of freezability for D-larvae quality assessment. This research contributes to the development of more effective cryopreservation protocols and detection methods for cryodamage in this species.

Ficus Genome Database: A Comprehensive Genomics and Transcriptomics Research Platform

Ficus is a significant genus within the Moraceae family, primarily native to tropical and subtropical regions. It plays a crucial role in the study of co-evolution and genetics in the fig–fig wasp symbiosis. Advancements in sequencing technology have facilitated whole-genome sequencing of several Ficus species, accumulating vast amounts of genomic and transcriptomic data available in public databases. To streamline data integration, display, and analysis, we developed the Ficus Genome Database (FGD), a consolidated platform for the genomic data of five Ficus species, and self-assembled transcriptome data for 24 fig ostiolar bracts. The FGD is currently home to a diverse array of data, encompassing genome and gene sequences, annotations of genes, transcriptome analyses, biochemical pathways, non-coding RNA, and findings from comparative genomic studies, such as collinear blocks across different Ficus genome assemblies. To enhance translational and practical research concerning Ficus, FGD provides an extensive suite of accessible query interfaces, analytical instruments, and visualization options. These include the NCBI BLAST sequence search tool and the JBrowse/GBrowse genome browser. FGD also offers several distinct tools, including a genome Synteny Viewer, expression heatmap display, gene family identification, Gene Ontology terms enrichment, and pathway enrichment analysis.

Differential expression analyses and detection of SNP loci associated with environmental variables: Are salinity and temperature factors involved in population differentiation and speciation in Odontesthes?

Environmental factors play a key role in individual adaptation to different local conditions. Because of this, studies about the physiological and genetic responses of individuals exposed to different natural environments offer clues about mechanisms involved in population differentiation, and as a subsequent result, speciation. Marine environments are especially suited to survey this kind of phenomena because they commonly harbor species adapted to different local conditions along a geographic continuum. Silversides belonging to Odontesthes are commonly distributed in tropical and temperate regions of South America and exhibit noticeable phenotypic plasticity, which allows them to adapt to contrasting environments. In this study, the genetic expression of O. argentinensis sampled along the Uruguayan Atlantic coast and estuarine adjacent areas was investigated. In addition, the correlation between individual genotypes and environmental variables was also analysed in O. argentinensis and O. bonariensis. Results obtained suggest a differential expression pattern of low magnitude among individuals from the different areas sampled and a correlation between several SNP loci and environmental variables. The analyses carried out did not show a clear differentiation among individuals sampled along different salinity regimens, but enriched GOTerms seem to be driven by water oxygen content. On the other hand, a total of 46 SNPs analysed in O. argentinensis and O. bonariensis showed a correlation with salinity and temperature. Although none of the correlated SNPs and corresponding genes from our both analyses were directly associated with hypoxia, genes related to the cardiovascular system and muscle cell differentiation were found. All these genes are interesting candidates for future studies since they are closely related to the differentially expressed genes. Although salinity was also mentioned as an important parameter limiting introgression between O. argentinensis and O. bonariensis, it was found that salinity does not drive differential expression in O. argentinensis, but rather oxygen levels. Moreover, salinity does not directly affect the structure and genetic divergence of the populations, they appear to be structured based on their degree of isolation and geographical distance between them. Further studies, like genome-wide analyses, could help to elucidate additional genes adapted to the different environments in these silverside species.

Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer

BackgroundTraditional Chinese medicine (TCM) has been found widespread application in neoplasm treatment, yielding promising therapeutic candidates. Previous studies have revealed the anti-cancer properties of Brevilin A, a naturally occurring sesquiterpene lactone derived from Centipeda minima (L.) A.Br. (C. minima), a TCM herb, specifically against lung cancer. However, the underlying mechanisms of its effects remain elusive. This study employs network pharmacology and experimental analyses to unravel the molecular mechanisms of Brevilin A in lung cancer.MethodsThe Batman-TCM, Swiss Target Prediction, Pharmmapper, SuperPred, and BindingDB databases were screened to identify Brevilin A targets. Lung cancer-related targets were sourced from GEO, Genecards, OMIM, TTD, and Drugbank databases. Utilizing Cytoscape software, a protein-protein interaction (PPI) network was established. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), and gene-pathway correlation analysis were conducted using R software. To validate network pharmacology results, molecular docking, molecular dynamics simulations, and in vitro experiments were performed.ResultsWe identified 599 Brevilin A-associated targets and 3864 lung cancer-related targets, with 155 overlapping genes considered as candidate targets for Brevilin A against lung cancer. The PPI network highlighted STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets. GO and KEGG analyses revealed 2893 enriched GO terms and 157 enriched KEGG pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. GSEA demonstrated a close association between hub genes and lung cancer. Gene-pathway correlation analysis indicated significant associations between hub genes and the cellular response to hypoxia pathway. Molecular docking and dynamics simulations confirmed Brevilin A’s interaction with PTEN and HIF1A, respectively. In vitro experiments demonstrated Brevilin A-induced dose- and time-dependent cell death in A549 cells. Notably, Brevilin A treatment significantly reduced HIF-1α mRNA expression while increasing PTEN mRNA levels.ConclusionsThis study demonstrates that Brevilin A exerts anti-cancer effects in treating lung cancer through a multi-target and multi-pathway manner, with the HIF pathway potentially being involved. These results lay a theoretical foundation for the prospective clinical application of Brevilin A.

RNAi-mediated knockdown of papilin gene affects the egg hatching in Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

Bioinformatics and Gene Expression Omnibus Analysis of Key Candidate Genes and Pathways Associated with Femoral Head Necrosis

Background: Femoral head necrosis (FHN) is a debilitating bone disease affecting an estimated 8 million people worldwide. Although specific drugs for FHN have limitations, targeted therapies have shown promising results. The significance of this study is underscored by the high prevalence of FHN, the limitations of current treatments, and the potential of targeted drugs and natural compounds for effective therapeutic interventions. Objectives: This study aimed to explore the genetic landscape and associated pathways of FHN through bioinformatics analysis of Gene Expression Omnibus (GEO) data and molecular docking simulations targeting specific enzymes implicated in FHN. Methods: Differentially expressed genes (DEGs) in FHN samples were identified from GEO datasets, specifically accession number GSE123568 (Platform: GPL15207). Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify enriched pathways and Gene Ontology (GO) terms. Additionally, a protein-protein interaction (PPI) network was constructed using the STITCH (search tool for interaction of chemicals) database, which helped identify top hub genes and proteins. Molecular docking was conducted against key proteins using compounds from the topical chinese herbal medicine (TCHM) database associated with FHN. Results: The study provided a comprehensive bioinformatics analysis of key candidate genes and pathways associated with FHN, which may serve as potential therapeutic targets. It was found that FHN is associated with mitogen-activated protein kinases (MAP4K4/ MAPK8/ MAPK9) and interleukins (IL1b/ IL19/ IL26). Molecular docking results showed strong interactions of traditional Chinese herbal compounds through hydrogen bonding and electrostatic interactions at the active sites of the top ten target proteins associated with FHN. Conclusions: The study confirmed that FHN is linked with enzymes such as mitogen-activated protein kinases (MAPKs), interleukins, tumor necrosis factors (TNFs), and VEGFA (vascular endothelial growth factor A). Molecular docking simulations demonstrated that hesperidin, naringin, and curcumin exhibit potent inhibition against key proteins involved in FHN. Future research will focus on elucidating the specific roles of genes associated with FHN and exploring potential therapeutic targets using natural compounds.

Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response

BackgroundMonths after infection with SARS-CoV-2, at least 10% of patients still experience complaints. Long-COVID is a heterogeneous disease and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. ObjectivesThis study aims to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. MethodsBlood was collected from 77 patients with long-COVID from the P4O2 COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analysed for differences in clinical features, pulmonary function tests and gene ontology (GO) term enrichment. ResultsClustering revealed two distinct clusters on a transcriptome level. Compared to cluster 2 (n=65), patients in cluster 1 (n=12) showed a higher rate of pre-existing cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during SARS-CoV-2 infection (median: 3 vs 8 days), lower Tiffeneau index (72% vs 81%) and lower diffusion capacity of the lung for carbon monoxide (DLCO) (68% vs 85% predicted). GO-term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, while genes involved with the adaptive immune response were upregulated in cluster 2. ConclusionThis study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.

Characterization of the Hepatic Transcriptome for Divergent Immune-Responding Sheep Following Natural Exposure to Gastrointestinal Nematodes.

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host's response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high (n = 5) or medium (n = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls (n = 4), and with biased antibody-mediated (AbMR, n = 5) or cell-mediated (CMR, n = 5) adaptive immune responsiveness compared to uninfected controls (n = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection.