Expression Of Various Genes Research Articles

Thermoregulated transcriptomics: the molecular basis and biological significance of temperature-dependent alternative splicing.

Temperature-dependent alternative splicing (AS) is a crucial mechanism for organisms to adapt to varying environmental temperatures. In mammals, even slight fluctuations in body temperature are sufficient to drive significant AS changes in a concerted manner. This dynamic regulation allows organisms to finely tune gene expression and protein isoform diversity in response to temperature cues, ensuring proper cellular function and physiological adaptation. Understanding the molecular mechanisms underlying temperature-dependent AS thus provides valuable insights into the intricate interplay between environmental stimuli and gene expression regulation. In this review, we provide an overview of recent advances in understanding temperature-regulated AS across various biological processes and systems. We will discuss the machinery sensing and translating temperature cues into changed AS patterns, the adaptation of the splicing regulatory machinery to extreme temperatures, the role of temperature-dependent AS in shaping the transcriptome, functional implications and the development of potential therapeutics targeting temperature-sensitive AS pathways.

Response signatures of intestinal microbiota and gene transcription of yellow catfish (Pelteobagrus fulvidraco) to Aeromonas hydrophila infection

Bacterial intestinal inflammation is a common disease of yellow catfish (Pelteobagrus fulvidraco) in high-density aquaculture. Understanding the interactions between host and intestinal bacteria is helpful to intestinal inflammatory disease control. Here, we constructed a model of intestinal inflammation after Aeromonas hydrophila infection in yellow catfish, and characterized variations in gene expression and microbiome in the gut through high-throughput sequencing. Furthermore, host gene-microbiome interactions were identified. Histology observation showed disordered distribution of columnar epithelial cells and decrease of goblet cells in intestine. A total of 4741 genes showed differentially expression, mostly in comparisons between 12 hpi group with each other groups respectively, including control, 24 hpi and 48 hpi groups. These genes were enriched in immune-related pathways including the IL-17 signaling pathway, triggering strong inflammatory response at the invading stage within 12 h. Subsequently, the host strengthened energy consumption by activating carbohydrate and lipid metabolism pathways to repair the intestinal mucosal immune defense line. In addition, fish with A. hydrophila infection show decreased richness of gut microbial, reduced relative abundance of probiotics including Akkermansia, and elevated pathogenic bacteria such as Plesimonas. An integrative analysis identified A. hydrophila-related genes, such as il22 and stat3, for which expression level is close associated with the shift of A. hydrophila-related bacteria relative abundance, such as Akkermansia and Cetobacterium. Aside from picturing the variations of intestine gene expression and mucosal microbiome of yellow catfish coping with A. hydrophila infection, our study probed the underlying host-microbe interactions in A. hydrophila infection induced intestinal inflammatory, providing new insights for disease control in aquaculture.

Characterization of GPX Gene Family in Pepper (Capsicum annuum L.) under Abiotic Stress and ABA Treatment.

Plant glutathione peroxidases (GPXs) are important enzymes for removing reactive oxygen species in plant cells and are closely related to the stress resistance of plants. This study identified the GPX gene family members of pepper (Capsicum annuum L.), "CM333", at the whole-genome level to clarify their expression patterns and enzyme activity changes under abiotic stress and ABA treatment. The results showed that eight CaGPX genes were unevenly distributed across four chromosomes and one scaffold of the pepper genome, and their protein sequences had Cys residues typical of the plant GPX domains. The analysis of collinearity, phylogenetic tree, gene structure, and conserved motifs indicated that the CaGPX gene sequence is conserved, structurally similar, and more closely related to the sequence structure of Arabidopsis. Meanwhile, many cis elements involved in stress, hormones, development, and light response were found in the promoter region of the CaGPX gene. In addition, CaGPX1/4 and CaGPX6 were basically expressed in all tissues, and their expression levels were significantly upregulated under abiotic stress and ABA treatment. Subcellular localization showed that CaGPX1 and CaGPX4 are localized in chloroplasts. Additionally, the variations in glutathione peroxidase activity (GSH-Px) mostly agreed with the variations in gene expression. In summary, the CaGPXs gene may play an important role in the development of peppers and their response to abiotic stress and hormones.

Aging trajectories of memory CD8 + T cells differ by their antigen specificity.

Memory T cells are a highly dynamic and heterogeneous population that is maintained by cytokine-driven homeostatic proliferation interspersed with episodes of antigen-mediated expansion and contraction which affect their functional state and their durability. This heterogeneity complicates studies on the impact of aging on global human memory cells, specifically, it is unclear how aging drives memory T cell dysfunction. Here, we used chronic infection with Epstein-Barr virus (EBV) to assess the influence of age on memory states at the level of antigen-specific CD8 + T cells. We find that in young adults (<40 years), EBV-specific CD8 + T cells assume preferred differentiation states depending on their peptide specificity. By age >65-years, different T cell specificities had undergone largely distinct aging trajectories, which had in common a loss in adaptive and a gain in innate immunity signatures. No evidence was seen for cellular senescence or exhaustion. While naïve/stem-like EBV-specific T cells disappeared with age, T cell diversity of EBV-specific memory cells did not change or even increased. In summary, by controlling for antigen specificity we uncover age-associated shifts in gene expression and TCR diversity that have implications for optimizing vaccination strategies and adoptive T cell therapy.

Two novel genomes of fireflies with different degrees of sexual dimorphism reveal insights into sex-biased gene expression and dosage compensation

Sexual dimorphism arises because of divergent fitness optima between the sexes. Phenotypic divergence between sexes can range from mild to extreme. Fireflies, bioluminescent beetles, present various degrees of sexual dimorphism, with species showing very mild sexual dimorphism to species presenting female-specific neoteny, posing a unique framework to investigate the evolution of sexually dimorphic traits across species. In this work, we present novel assembled genomes of two firefly species, Lamprohiza splendidula and Luciola italica, species with different degrees of sexual dimorphism. We uncover high synteny conservation of the X-chromosome across ~ 180 Mya and find full X-chromosome dosage compensation in our two fireflies, hinting at common mechanism upregulating the single male X-chromosome. Different degrees of sex-biased expressed genes were found across two body parts showing different proportions of expression conservation between species. Interestingly, we do not find X-chromosome enrichment of sex-biased genes, but retrieve autosomal enrichment of sex-biased genes. We further uncover higher nucleotide diversity in the intronic regions of sex-biased genes, hinting at a maintenance of heterozygosity through sexual selection. We identify different levels of sex-biased gene expression divergence including a set of genes showing conserved sex-biased gene expression between species. Divergent and conserved sex-biased genes are good candidates to test their role in the maintenance of sexually dimorphic traits.

A real-world multi-center RNA-seq benchmarking study using the Quartet and MAQC reference materials

Translating RNA-seq into clinical diagnostics requires ensuring the reliability and cross-laboratory consistency of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. As part of the Quartet project, we present an RNA-seq benchmarking study across 45 laboratories using the Quartet and MAQC reference samples spiked with ERCC controls. Based on multiple types of ‘ground truth’, we systematically assess the real-world RNA-seq performance and investigate the influencing factors involved in 26 experimental processes and 140 bioinformatics pipelines. Here we show greater inter-laboratory variations in detecting subtle differential expressions among the Quartet samples. Experimental factors including mRNA enrichment and strandedness, and each bioinformatics step, emerge as primary sources of variations in gene expression. We underscore the profound influence of experimental execution, and provide best practice recommendations for experimental designs, strategies for filtering low-expression genes, and the optimal gene annotation and analysis pipelines. In summary, this study lays the foundation for developing and quality control of RNA-seq for clinical diagnostic purposes.

A pan-cancer gamma delta T cell repertoire.

This report presents the largest collection of gamma-delta T cell receptor (γδ TCR) reads in human cancer to date, analyzing about 11,000 patient tumor samples across 33 cancer types using the TRUST4 algorithm. Despite γδ T cells being a small fraction of the T cell population, they play a key role in both innate and adaptive immunity. Our comprehensive analysis reveals their significant presence across all cancer types, specifically highlighting the diverse spectrum and clonality patterns of their γδ receptors. This research highlights the complex roles of γδ T cells in tumor tissues and their potential as prognostic biomarkers. We also demonstrate the utility of T cell receptor gamma (TRG) and delta (TRD) gene expression values from standard RNA-seq data. Ultimately, our work establishes a fundamental resource for future tumor-infiltrating γδ T cell research and may facilitate the development of novel γδ-T-cell-based therapeutic strategies. Together, we demonstrate the strong diversity and prognostic potential of γδ T cells in multiple cancer types.

Sources of gene expression variation in a globally diverse human cohort.

Genetic variation that influences gene expression and splicing is a key source of phenotypic diversity1-5. Although invaluable, studies investigating these links in humans have been strongly biased towards participants of European ancestries, which constrains generalizability and hinders evolutionary research. Here to address these limitations, we developed MAGE, an open-access RNA sequencing dataset of lymphoblastoid cell lines from 731 individuals from the 1000 Genomes Project6, spread across 5 continental groups and 26 populations. Most variation in gene expression (92%) and splicing (95%) was distributed within versus between populations, which mirrored the variation in DNA sequence. We mapped associations between genetic variants and expression and splicing of nearby genes (cis-expression quantitative trait loci (eQTLs) and cis-splicing QTLs (sQTLs), respectively). We identified more than 15,000 putatively causal eQTLs and more than 16,000 putatively causal sQTLs that are enriched for relevant epigenomic signatures. These include 1,310 eQTLs and 1,657 sQTLs that are largely private to underrepresented populations. Our data further indicate that the magnitude and direction of causal eQTL effects are highly consistent across populations. Moreover, the apparent 'population-specific' effects observed in previous studies were largely driven by low resolution or additional independent eQTLs of the same genes that were not detected. Together, our study expands our understanding of human gene expression diversity and provides an inclusive resource for studying the evolution and function of human genomes.

Evolution of the regulation of developmental gene expression in blind Mexican cavefish.

Developmental evolution and diversification of morphology can arise through changes in the regulation of gene expression or protein-coding sequence. To unravel mechanisms underlying early developmental evolution in cavefish of the species Astyanax mexicanus, we compared transcriptomes of surface-dwelling and blind cave-adapted morphs at the end of gastrulation. Twenty percent of the transcriptome was differentially expressed. Allelic expression ratios in cave X surface hybrids showed that cis-regulatory changes are the quasi-exclusive contributors to inter-morph variations in gene expression. Among a list of 108 genes with change at the cis-regulatory level, we explored the control of expression of rx3, which is a master eye gene. We discovered that cellular rx3 levels are cis-regulated in a cell-autonomous manner, whereas rx3 domain size depends on non-autonomous Wnt and Bmp signalling. These results highlight how uncoupled mechanisms and regulatory modules control developmental gene expression and shape morphological changes. Finally, a transcriptome-wide search for fixed coding mutations and differential exon use suggested that variations in coding sequence have a minor contribution. Thus, during early embryogenesis, changes in gene expression regulation are the main drivers of cavefish developmental evolution.

Single-cell level LasR-mediated quorum sensing response of Pseudomonas aeruginosa to pulses of signal molecules

Quorum sensing (QS) is a communication form between bacteria via small signal molecules that enables global gene regulation as a function of cell density. We applied a microfluidic mother machine to study the kinetics of the QS response of Pseudomonas aeruginosa bacteria to additions and withdrawals of signal molecules. We traced the fast buildup and the subsequent considerably slower decay of a population-level and single-cell-level QS response. We applied a mathematical model to explain the results quantitatively. We found significant heterogeneity in QS on the single-cell level, which may result from variations in quorum-controlled gene expression and protein degradation. Heterogeneity correlates with cell lineage history, too. We used single-cell data to define and quantitatively characterize the population-level quorum state. We found that the population-level QS response is well-defined. The buildup of the quorum is fast upon signal molecule addition. At the same time, its decay is much slower following signal withdrawal, and the quorum may be maintained for several hours in the absence of the signal. Furthermore, the quorum sensing response of the population was largely repeatable in subsequent pulses of signal molecules.

IGF1R and FLT1 in female endothelial cells and CHD2 in male microglia play important roles in Alzheimer's disease based on gender difference analysis

ObjectiveThis study investigated sex-specific pathogenesis mechanisms in Alzheimer's disease (AD) using single-nucleus RNA sequencing (snRNA-seq) data. MethodsData from the Gene Expression Omnibus (GEO) were searched using terms “Alzheimer's Disease”, “single cell”, and “Homo sapiens”. Studies excluding APOE E4 and including comprehensive gender information with 10× sequencing methods were selected, resulting in GSE157827 and GSE174367 datasets from human prefrontal cortex samples. Sex-stratified analyses were conducted on these datasets, and the outcomes of the analysis for GSE157827 were compared with those of GSE174367. The findings were validated using expression profiling from the mouse dataset GSE85162. Furthermore, real-time PCR experiments in mice further confirmed these findings. The Seurat R package was used to identify cell types, and batch effects were mitigated using the Harmony R package. Cell proportions by sex were compared using the Mann-Whitney-Wilcoxon test, and gene expression variability was displayed with an empirical cumulative distribution plot. Differentially expressed genes were identified using the FindMarkers function with the MAST test. Transcription factors were analyzed using the RcisTarget R package. ResultsSeven cell types were identified: astrocytes, endothelial cells, excitatory neurons, inhibitory neurons, microglia, oligodendrocytes, and oligodendrocyte progenitor cells. Additionally, five distinct subpopulations of both endothelial and microglial cells were also identified, respectively. Key findings included: (1) In endothelial cells, genes involved in synapse organization, such as Insulin Like Growth Factor 1 Receptor (IGF1R) and Fms Related Receptor Tyrosine Kinase 1(FLT1), showed higher expression in females with AD. (2) In microglial cells, genes in the ribosome pathway exhibited higher expression in males without AD compared to females (with or without AD) and males with AD. (3) Chromodomain Helicase DNA Binding Protein 2 (CHD2) negatively regulated gene expression in the ribosome pathway in male microglia, suppressing AD, this finding was further validated in mice. (4) Differences between Asians and Caucasians were observed based on sex and disease status stratification. ConclusionsIGF1R and FLT1 in endothelial cells contribute to AD in females, while CHD2 negatively regulates ribosome pathway gene expression in male microglia, suppressing AD in humans and mice.

DNA Methylation of the Autonomous Pathway Is Associated with Flowering Time Variations in Arabidopsis thaliana.

Plant flowering time is affected by endogenous and exogenous factors, but its variation patterns among different populations of a species has not been fully established. In this study, 27 Arabidopsis thaliana accessions were used to investigate the relationship between autonomous pathway gene methylation, gene expression and flowering time variation. DNA methylation analysis, RT-qPCR and transgenic verification showed that variation in the flowering time among the Arabidopsis populations ranged from 19 to 55 days and was significantly correlated with methylation of the coding regions of six upstream genes in the autonomous pathway, FLOWERING LOCUS VE (FVE), FLOWERING LOCUS Y (FY), FLOWERING LOCUS D (FLD), PEPPER (PEP), HISTONE DEACETYLASE 5 (HAD5) and Pre-mRNA Processing Protein 39-1 (PRP39-1), as well as their relative expression levels. The expression of FVE and FVE(CS) was modified separately through degenerate codon substitution of cytosine and led to earlier flowering of transgenic plants by 8 days and 25 days, respectively. An accurate determination of methylated sites in FVE and FVE(CS) among those transgenic plants and the recipient Col-0 verified the close relationship between the number of methylation sites, expression and flowering time. Our findings suggest that the methylation variation of these six key upstream transcription factors was associated with the gene expression level of the autonomous pathway and flowering time in Arabidopsis. The FVE(CS) and FVE genes in transgenic plants tended to be hypermethylated, which could be a protective mechanism for plants. However, modification of gene sequences through degenerate codon substitution to reduce cytosine can avoid hypermethylated transferred genes in transgenic plants. It may be possible to partially regulate the flowering of plants by modified trans-epigenetic technology.

Rapid evolution of promoters from germline-specifically expressed genes including transposon silencing factors

BackgroundThe piRNA pathway in animal gonads functions as an ‘RNA-based immune system’, serving to silence transposable elements and prevent inheritance of novel invaders. In Drosophila, this pathway relies on three gonad-specific Argonaute proteins (Argonaute-3, Aubergine and Piwi) that associate with 23–28 nucleotide piRNAs, directing the silencing of transposon-derived transcripts. Transposons constitute a primary driver of genome evolution, yet the evolution of piRNA pathway factors has not received in-depth exploration. Specifically, channel nuclear pore proteins, which impact piRNA processing, exhibit regions of rapid evolution in their promoters. Consequently, the question arises whether such a mode of evolution is a general feature of transposon silencing pathways.ResultsBy employing genomic analysis of coding and promoter regions within genes that function in transposon silencing in Drosophila, we demonstrate that the promoters of germ cell-specific piRNA factors are undergoing rapid evolution. Our findings indicate that rapid promoter evolution is a common trait among piRNA factors engaged in germline silencing across insect species, potentially contributing to gene expression divergence in closely related taxa. Furthermore, we observe that the promoters of genes exclusively expressed in germ cells generally exhibit rapid evolution, with some divergence in gene expression.ConclusionOur results suggest that increased germline promoter evolution, in partnership with other factors, could contribute to transposon silencing and evolution of species through differential expression of genes driven by invading transposons.

Transgenic early japonica rice: Integration and expression characterization of stem borer resistance Bt gene

BackgroundTransgenic insect-resistant rice offers an environmentally friendly approach to mitigate yield losses caused by lepidopteran pests, such as stem borers. Bt (Bacillus thuringiensis) genes encode insecticidal proteins and are widely used to confer insect resistance to genetically modified crops. This study investigated the integration, inheritance, and expression characteristics of codon-optimised synthetic Bt genes, cry1C* and cry2A*, in transgenic early japonica rice lines. MethodsThe early japonica rice cultivar, Songgeng 9 (Oryza sativa), was transformed with cry1C* or cry2A*, which are driven by the ubi promoter via Agrobacterium tumefaciens-mediated transformation. Molecular analyses, including quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and Southern blot analysis were performed to confirm transgene integration, inheritance, transcriptional levels, and protein expression patterns across different tissues and developmental stages. ResultsStable transgenic early japonica lines exhibiting single-copy transgene integration were established. Transcriptional analysis revealed variations in Bt gene expression among lines, tissues, and growth stages, with higher expression levels observed in leaves than in other organs. Notably, cry2A* exhibited consistently higher mRNA and protein levels than cry1C* across all examined tissues and developmental time points. Bt protein accumulation followed the trend of leaves > stem sheaths > young panicles > brown rice, with peak expression during the filling stage in the vegetative tissues. ConclusionsSynthetic cry2A* displayed markedly elevated transcription and translation compared to cry1C* in the transgenic early japonica rice lines examined. Distinct spatiotemporal patterns of Bt gene expression were elucidated, providing insights into the potential insect resistance conferred by these genes in rice. These findings will contribute to the development of insect-resistant japonica rice varieties and facilitate the rational deployment of Bt crops.

Reliable Genomic Integration Sites in Pseudomonas putida Identified by Two-Dimensional Transcriptome Analysis.

Genomic integration is commonly used to engineer stable production hosts. However, so far, for many microbial workhorses, only a few integration sites have been characterized, thereby restraining advanced strain engineering that requires multiple insertions. Here, we report on the identification of novel genomic integration sites, so-called landing pads, for Pseudomonas putida KT2440. We identified genomic regions with constant expression patterns under diverse experimental conditions by using RNA-Seq data. Homologous recombination constructs were designed to insert heterologous genes into intergenic sites in these regions, allowing condition-independent gene expression. Ten potential landing pads were characterized using four different msfGFP expression cassettes. An insulated probe sensor was used to study locus-dependent effects on recombinant gene expression, excluding genomic read-through of flanking promoters under changing cultivation conditions. While the reproducibility of expression in the landing pads was very high, the msfGFP signals varied strongly between the different landing pads, confirming a strong influence of the genomic context. To showcase that the identified landing pads are also suitable candidates for heterologous gene expression in other Pseudomonads, four equivalent landing pads were identified and characterized in Pseudomonas taiwanensis VLB120. This study shows that genomic "hot" and "cold" spots exist, causing strong promoter-independent variations in gene expression. This highlights that the genomic context is an additional parameter to consider when designing integrable genomic cassettes for tailored heterologous expression. The set of characterized genomic landing pads presented here further increases the genetic toolbox for deep metabolic engineering in Pseudomonads.

Deciphering the cis-regulatory landscape of natural yeast Transcript Leaders.

Protein synthesis is a vital process that is highly regulated at the initiation step of translation. Eukaryotic 5' transcript leaders (TLs) contain a variety of cis-regulatory features that influence translation and mRNA stability. However, the relative influences of these features in natural TLs are poorly characterized. To address this, we used massively parallel reporter assays (MPRAs) to quantify RNA levels, ribosome loading, and protein levels from 11,027 natural yeast TLs in vivo and systematically compared the relative impacts of their sequence features on gene expression. We found that yeast TLs influence gene expression over two orders of magnitude. While a leaky scanning model using Kozak contexts and uAUGs explained half of the variance in expression across transcript leaders, the addition of other features explained ~70% of gene expression variation. Our analyses detected key cis-acting sequence features, quantified their effects in vivo, and compared their roles to motifs reported from an in vitro study of ribosome recruitment. In addition, our work quantitated the effects of alternative transcription start site usage on gene expression in yeast. Thus, our study provides new quantitative insights into the roles of TL cis-acting sequences in regulating gene expression.

The link between gene duplication and divergent patterns of gene expression across a complex life cycle.

The diversification of many lineages throughout natural history has frequently been associated with evolutionary changes in life cycle complexity. However, our understanding of the processes that facilitate differentiation in the morphologies and functions expressed by organisms throughout their life cycles is limited. Theory suggests that the expression of traits is decoupled across life stages, thus allowing for their evolutionary independence. Although trait decoupling between stages is well established, explanations of how said decoupling evolves have seldom been considered. Because the different phenotypes expressed by organisms throughout their life cycles are coded for by the same genome, trait decoupling must be mediated through divergence in gene expression between stages. Gene duplication has been identified as an important mechanism that enables divergence in gene function and expression between cells and tissues. Because stage transitions across life cycles require changes in tissue types and functions, we investigated the potential link between gene duplication and expression divergence between life stages. To explore this idea, we examined the temporal changes in gene expression across the monarch butterfly (Danaus plexippus) metamorphosis. We found that within homologous groups, more phylogenetically diverged genes exhibited more distinct temporal expression patterns. This relationship scaled such that more phylogenetically diverse homologous groups showed more diverse patterns of gene expression. Furthermore, we found that duplicate genes showed increased stage-specificity relative to singleton genes. Overall, our findings suggest an important link between gene duplication and the evolution of complex life cycles.

Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study

BackgroundCervical cancer’s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes’ immune gene expression profiles and immunoregulation mechanisms have...

Unraveling genetic threads: Identifying novel therapeutic targets for allergic rhinitis through Mendelian randomization

BackgroundAllergic rhinitis (AR) is a pervasive global health issue, and currently, there is a scarcity of targeted drug therapies available. This study aims to identify potential druggable target genes for AR using Mendelian randomization (MR) analysis. MethodsMR analysis was conducted to assess the causal effect of expression quantitative trait loci (eQTL) in the blood on AR. Data on AR were collected from 2 datasets: FinnGen(R9) (11,009 cases and 359,149 controls) and UK Biobank (25,486 cases and 87,097 controls). Colocalization analysis was utilized to assess the common causal genetic variations between the identified drug target genes and AR. We also employed available genome-wide association studies (GWAS) data to gauge the impact of druggable genes on AR biomarkers and other allergic diseases. ResultsThis study employs MR to analyze the relationship between 3410 druggable genes and AR. After Bonferroni correction, 10 genes were found to be significantly associated with AR risk (P < 0.05/3410). Colocalization analysis revealed a significant causal relationship between the expression variation of CFL1 and EFEMP2 genes and AR, sharing direct causal variants (colocalization probability PP.H3 + PP.H4 > 0.8), highlighting their importance as potential therapeutic targets for AR. The CFL1 gene showed a causal link with levels of thymic stromal lymphopoietin (TSLP), eosinophil count, and interleukin-13 (IL-13) (P = 0.016, 7.45E-16, 0.00091, respectively). EFEMP2 was also causally related to eosinophil count, IL-13, and interleukin-17 (IL-17) (P = 0.00012, 0.00091, 0.032, respectively). PheWAS analysis revealed significant associations of CFL1 with asthma, whereas EFEMP2 showed associations with both asthma and eczema. Protein-Protein Interaction (PPI) network analysis further unveiled the direct interactions of EFEMP2 and CFL1 with proteins related to immune regulation and inflammatory responses, with 77.64% of the network consisting of direct bindings, indicating their key roles in modulating AR-related immune and inflammatory responses. Notably, there was an 8.01% significant correlation between immune-related pathways and genes involved in inflammatory responses. ConclusionThese genes present notable associations with AR biomarkers and other autoimmune diseases, offering valuable targets for developing new AR therapies.

The Incidence of CD28 Gene Polymorphism (rs3116496) and Gene Expression with Oral Carcinoma in Some Iraqi Samples

Abstract Background: Oral carcinoma is one kind of cancer that develops in the cavity of the oral, lip, tongue, gingiva, and oropharynx. The World Health Organization (WHO) illustrated that oral carcinoma is among the most prevalent cancers in the world, considered the sixteenth most malignant, which is commonly prevalent, and the fifteenth reason that causes mortality in the world. Objective: This study aimed to investigate the association between oral carcinoma with single-nucleotide polymorphism (rs3116496) and CD28 (cluster differentiation 28) gene expression. Materials and Methods: Samples were collected from 61 control and 61 patients with early squamous oral carcinoma from the gum diseases department/Fallujah specialized center. Then we investigated the variation of CD28 polymorphism and gene expression of CD28 using real-time PCR. Results: The results showed that there are significant differences between patients and control in the TT genotype of codominant models with P = 0.003 and OR = 8.89. There were significant differences in the dominant and recessive models with P = 0.03 and 0.008, and OR = 2.4, 7.2, respectively. In addition, the T allele showed significant differences between patients and control with P = 0.002 and OR = 2.61. However, in the CD28 gene expression there were no significant differences between patients and control. Conclusion: The genotype TT and allele T of SNP of the CD28 gene are considered risk factors in oral carcinoma.