Alterations in the gut microbiota and their metabolites in human intestinal epithelial cells of patients with colorectal cancer.

BACKGROUND: The gut microbiota has become one of the main risk factors for the formation and development of colorectal cancer (CRC). CRC intensification may be due to the microbial pathogens' colonization and their released metabolites. Here, we analyzed Bacteroidetes and Clostridia bacteria in CRC patients and studied bacterial metabolome in cancerous tissues compared to their adjacent normal tissues. METHODS AND RESULTS: The population of selected bacteria in biopsy specimens of 30 patients with CRC was studied by RT-qPCR. The mutagenicity and cytotoxicity effects of microbiota metabolites were evaluated by Ames test and MTT Assay, respectively. Moreover, gene expression in carcinogenic pathways was studied by RT-qPCR, and genes with different expressions in tumor and non-tumor tissues were diagnosed. Based on microbiota analysis, the relative abundance of Clostridia and C. difficile was significantly higher in CRC tissue, whereas C. perfringens showed higher relative abundance in normal tissue. AIMES test confirmed the proliferation and mutagenicity effects of the bacterial metabolites in CRC patients. Significant upregulation of C-Myc, GRB2, IL-8, EGFR, PI3K, and AKT and downregulation of ATM were observed in CRC samples compared to the control. CONCLUSIONS: The influence of bacterial metabolites on inflammation and altered expression of genes in the cell signaling pathways was observed. The findings confirm the role gut microbiota composition and bacterial metabolites as key players in CRC onset and development.

The role of mir-197-3p in regulating the tight junction permeability of celiac disease patients under gluten free diet.

BACKGROUND: Celiac disease (CD) is a hereditary immune-mediated disorder, which is along with the enormous production of pro-inflammatory cytokines and the reduced level of tight junction proteins. The aim of this study was to determine the expression of TNF-α, IFN-γ, IL-18, Occludin, miR-122-5p and miR-197-3p genes in duodenal biopsies of treated CD patients in comparison to the controls. METHODS AND RESULTS: Biopsy specimens were taken from the duodenum of 50 treated CD patients (36 (72%) females and 14 (28%) males with mean age of 37.06 ± 7.02 years) and 50 healthy controls (17 (34%) females and 33 (66%) males with mean age of 34.12 ± 4.9). Total RNA was isolated, cDNA was synthesized and mRNA expression of TNF-α, IFN-γ, IL-18, Occludin, miR-122-5p and miR-197-3p were quantified by relative qPCR using B2M and U6 as internal control genes. All data were evaluated using SPSS (V.21) and GraphPad Prism (V.5). Our results showed that there was no significant difference between patients and controls for intestinal mRNA expression of TNF-α, IFN-γ, IL-18, Occludin, and miR-122-5p (p > 0.05) and the expression of miR-197-3p was significantly increased in CD patients relative to control subjects (p = 0.049). CONCLUSION: This study suggests that adherence to GFD may have a positive effect on the tight junction (TJ) permeability and in this process, miR-197-3p plays an important role. Increased expression of miR-197-3p with a final protective effect on Occludin expression can be further studied as a complement therapeutic target for Celiac disease.

The connection between fatty acids and inflammation in celiac disease; a deep exploring.

The interplay between fatty acids (FAs) and celiac disease (CD) is a burgeoning field of research with significant implications for understanding the pathophysiology and potential therapeutic avenues for this autoimmune disorder. CD, triggered by gluten consumption in susceptible individuals, presents with a range of intestinal and extra-intestinal symptoms impacting various bodily functions. The disruption of intestinal tight junctions (TJs) by gluten proteins leads to increased gut permeability and subsequent inflammatory responses mediated by T-cells. FAs, crucial components of cell membranes, play diverse roles in inflammation and immune regulation. In fact, FAs have been shown to modulate inflammatory processes through various mechanisms. Studies have highlighted alterations in FA profiles in individuals with CD, indicating potential implications for disease pathogenesis and micronutrient deficiencies. Moreover, the exploration of FAs as biomarkers for CD diagnosis offers promising avenues for future research and therapeutic interventions. Understanding the intricate relationship between FAs and CD could lead to novel approaches in managing this complex autoimmune disorder. Therefore, this review article aims to provide an overview of the connection between FAs and inflammation in CD.

Overview of the compromised mucosal integrity in celiac disease.

Intestinal epithelium is a dynamic cellular layer that lines the small-bowel and makes a relatively impenetrable barrier to macromolecules. Intestinal epithelial cell polarity is crucial in coordinating signalling pathways within cells and mainly regulated by three conserved polarity protein complexes, the Crumbs (Crb) complex, partitioning defective (PAR) complex, and Scribble (Scrib) complex. Polarity proteins regulate the proper establishment of the intercellular junctional complexes including tight junctions (TJs), adherence junctions (AJs), and desmosomes which hold epithelial cells together and play a major role in maintaining intestinal barrier integrity. Impaired intestinal epithelial cell polarity and barrier integrity result in irreversible immune responses, the host- microbial imbalance and intestinal inflammatory disorders. Disassembling the epithelial tight junction and augmented paracellular permeability is a conspicuous hallmark of celiac disease (CD) pathogenesis. There are several dietary components that can improve intestinal integrity and function. The aim of this review article is to summarize current information about the association of polarity proteins and AJC damages with pathogenesis of CD.

Metabolomics and lipidomics signature in celiac disease: a narrative review.

Celiac disease (CD) is a chronic immune-mediated inflammatory disease of the small intestine caused by aberrant immune responses to consumed gluten proteins. CD is diagnosed by a combination of the patients reported symptoms, serologic and endoscopic biopsy evaluation of the small intestine; and adherence to a strict gluten-free diet (GFD) is considered the only available therapeutic approach for this disorder. Novel approaches need to be considered for finding new biomarkers to help this disorder diagnosis and finding a new alternative therapeutic method for this group of patients. Metabolomics and lipidomics are powerful tools to provide highly accurate and sensitive biomarkers. Previous studies indicated a metabolic fingerprint for CD deriving from alterations in gut microflora or intestinal permeability, malabsorption, and energy metabolism. Moreover, since CD is characterized by increased intestinal permeability and due to the importance of membrane lipid components in controlling barrier integrity, conducting lipidomics studies in this disorder is of great importance. In the current study, we tried to provide a critical overview of metabolomic and lipidomic changes in CD.

The link between gluten intake and the risk of cancers.

Gluten is a complex mixture of hundreds of related proteins, with the two major groups being gliadin and glutenin. Gliadin primarily affects the viscosity of dough, while glutenin contributes to its strength. Nowadays, there is evidence suggesting an increase in gluten exposure due to advancements in cereal technology. Consumption of gluten can lead to development of gluten-related disorders (GRDs) in susceptible individuals. Some GRDs have been strongly associated with an increased risk of developing certain types of cancer. Colorectal cancer and lymphoma are among the most commonly reported malignancies associated with GRDs. Dietary factors, including gluten intake, have been recognized as significant modifiable risk factors for the development of digestive system cancers. The present study aimed to collect current information on the effect of gluten on the incidence of cancer in the general population and among GRDs patients. Protein-Protein Interaction (PPI) Network analysis of common genes between celiac disease (CD) and cancer was also conducted.

The correlation between fecal microbiota profiles and intracellular junction genes expression in young Iranian patients with celiac disease.

Celiac disease (CD) is characterized by the disruption of the intestinal barrier integrity and alterations in the microbiota composition. This study aimed to evaluate the changes in the fecal microbiota profile and mRNA expressions of intracellular junction-related genes in pediatric patients with CD compared to healthy controls (HCs). Thirty treated CD patients, 10 active CD, and 40 HCs were recruited. Peripheral blood (PB) and fecal samples were collected. Microbiota analysis was performed using quantitative real-time PCR (qPCR) test. The mRNA expressions of ZO-1, occludin, ß-catenin, E-cadherin, and COX-2 were also evaluated. In active and treated CD patients, the PB expression levels of ZO-1 (p = 0.04 and 0.002, respectively) and ß-catenin (p = 0.006 and 0.02, respectively) were lower than in HCs. PB Occludin's level was upregulated in both active and treated CD patients compared to HCs (p = 0.04 and 0.02, respectively). However, PB E-cadherin and COX-2 expression levels and fecal mRNA expressions of ZO-1, occludin, and COX-2 did not differ significantly between cases and HCs (P˃0.05). Active CD patients had a higher relative abundance of the Firmicutes (p = 0.04) and Actinobacteria (p = 0.03) phyla compared to treated subjects. The relative abundance of Veillonella (p = 0.04) and Staphylococcus (p = 0.01) genera was lower in active patients in comparison to HCs. Researchers should explore the precise impact of the gut microbiome on the molecules and mechanisms involved in intestinal damage of CD. Special attention should be given to Bifidobacteria and Enterobacteriaceae, as they have shown a significant correlation with the expression of tight junction-related genes.

Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients.

OBJECTIVE: Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions. METHODS: Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test. RESULT: CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels. CONCLUSION: This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.

Introducing critical proteins related to liver ischemia/reperfusion injury.

Aim: The current study aimed to introduce the key proteins involved in liver ischemia/reperfusion (I/R) injury through protein-protein interaction (PPI) analysis. Background: Liver transplantation (LT) is a well-known treatment for liver diseases that threaten patients with mortality. LT is a complex operation, and several risks, including liver I/R injury, affect its success. Improving LT requires detection of its molecular mechanism. Experiments have revealed that high throughput methods such as proteomics in combination with bioinformatics are useful tools for analyzing the molecular mechanism of disease. Methods: The differentially expressed proteins (DEPs) involved in liver I/R injury were extracted from the literature. The queried DEPs plus the first 100 neighbors were included in a network through STRING database using Cytoscape software. Degree, betweenness centrality, closeness centrality, and stress were considered to determine the central nodes. The queried DEPs were assessed by action map analysis using the CluePedia application of Cytoscape software. The key proteins were identified by comparing network analysis and action map evaluation results. Results: Six proteins, namely ALB, INS, GAPDH, CAT, IL6, and TNF, among the added first neighbors were determined as the central first neighbors. MPO, CRP, MMP9, and HMOX1 were selected as central DEPs among the queried proteins. Action map analysis confirmed the PPI findings. The final evaluation revealed that MMP9 in combination with CRP and HMOX1 plays a critical role in liver I/R injury. Conclusion: The significant role of MMP9 in liver I/R injury was detected in this study. Two central proteins (CRP and HMOX1) were shown to have a regulatory effect on MMP9; CRP activated MMP9, while HMXO1 downregulated it.

Assessment of Recovery Time Effects on Human Primary Neonatal Dermal Fibroblasts After Exposure to Solar-Simulated Ultraviolet Radiation.

Introduction: Photoaging that is accompanied by gene expression alteration is known as early aging of the skin due to overexposure to natural and/or artificial ultraviolet radiation (UVR). The assessment of gene expression alteration in human primary neonatal dermal fibroblasts depending on recovery time after exposure to solar simulated ultraviolet radiation (ssUVR) is the main aim of this bioinformatic study. Methods: Data are extracted from Gene Expression Omnibus (GEO). The pre-evaluation is done via the GEO2R program. The Significant differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis, and the central genes were identified. The central genes were enriched via gene ontology assessment. Results: Among 224 significant DEGs, 20 central genes including TOP2A, MKI67, BRCA1, HELLS, MAD2L1, ANLN, KIF11, MSH2, KRAS, NCAPG, RFC3, PLK4, WDHD1, BLM, CDKN3, KIF15, SMARCA5, and ATAD2 as hub genes and TOP2A, MKI67, BRCA1, ANLN, KRAS, PLK4, SMARCA5, MMP2, and TLR4 as bottleneck genes were determined. Eight central genes were associated with 16 biological terms. Conclusion: In conclusion, significant differences appeared between gene expression conditions of the cells after 1-day and 5-day recovery. Molecular events include the repair and continuation of photodamages. It is possible to introduce drug targets to prevent the progress of induced damages.

The effectiveness of photobiomodulation therapy in modulation the gut microbiome dysbiosis related diseases.

Maintaining a healthy balance between commensal, and pathogenic bacteria within the gut microbiota is crucial for ensuring the overall health, and well-being of the host. In fact, by affecting innate, and adaptive immune responses, the gut microbiome plays a key role in maintaining intestinal homeostasis and barrier integrity. Dysbiosis is the loss of beneficial microorganisms and the growth of potentially hazardous microorganisms in a microbial community, which has been linked to numerous diseases. As the primary inducer of circadian rhythm, light can influence the human intestinal microbiome. Photobiomodulation therapy (PBMT), which is the use of red (630-700 nm), and near-infrared light (700 and 1200 nm), can stimulate healing, relieve pain, and reduce inflammation, and affect the circadian rhythm and gut microbiome beneficially. Our focus in this paper is on the effects of PBMT on gut microbiota, to provide an overview of how it can help control gut microbiota dysbiosis-related disorders.

The Gliadin Hydrolysis Capacity of B. longum, L. acidophilus, and L. plantarum and Their Protective Effects on Caco-2 Cells against Gliadin-Induced Inflammatory Responses.

BACKGROUND: Non-celiac wheat sensitivity (NCWS) is a poorly understood gluten-related disorder (GRD) and its prominent symptoms can be ameliorated by gluten avoidance. This study aimed to determine the effectiveness of a probiotic mixture in hydrolyzing gliadin peptides (toxic components of gluten) and suppressing gliadin-induced inflammatory responses in Caco-2 cells. METHODS: Wheat dough was fermented with a probiotic mix for 0, 2, 4, and 6 h. The effect of the probiotic mix on gliadin degradation was monitored by SDS-PAGE. The expression levels of IL-6, IL-17A, INF-γ, IL-10, and TGF-ß were evaluated using ELISA and qRT-PCR methods. RESULTS: According to our findings, fermenting wheat dough with a mix of B. longum, L. acidophilus, and L. plantarum for 6 h was effective in gliadin degradation. This process also reduced levels of IL-6 (p = 0.004), IL-17A (p = 0.004), and IFN-γ (p = 0.01) mRNA, as well as decreased IL-6 (p = 0.006) and IFN-γ (p = 0.0009) protein secretion. 4 h fermentation led to a significant decrease in IL-17A (p = 0.001) and IFN-γ (p = 0.003) mRNA, as well as reduced levels of IL-6 (p = 0.002) and IFN-γ (p < 0.0001) protein secretion. This process was also observed to increase the expression levels of IL-10 (p < 0.0001) and TGF-ß (p < 0.0001) mRNA. CONCLUSIONS: 4 h fermentation of wheat flour with the proposed probiotic mix might be a good strategy to develop an affordable gluten-free wheat dough for NCWS and probably other GRD patients.

Targeting colon cancer via antimicrobial RT2 peptide: a system biology study.

Aim: This study aims to investigate the anticancer molecular mechanism of RT2 through protein-protein interaction (PPI) network analysis. For this aim, a bioinformatics evaluation of the proteome profile of colon cancer is carried out. Background: Antimicrobial peptides such as RT2 showed anticancer properties against various tumors. The molecular mechanism of the anticancer effect of RT2 is a challenging subject. Methods: By applying Cytoscape V.3.9.1 and integrated apps, the profile of the interaction network and related centrality is analyzed. An enrichment analysis of hub bottlenecks was also performed, and highlighted biological processes were visualized and determined. Results: Several 207 differentially expressed proteins were retrieved by PPI network analysis, and 10 hub bottlenecks were introduced. Among these differentially expressed proteins (DEPs), only AKT1 is from the queried DEPs. Key biological processes contributing to RT2 targeting mechanism include "Regulation of fibroblast proliferation", "Positive regulation of cyclin-dependent protein serine/threonine kinase activity", "positive regulation of miRNA transcription", and "fungiform papilla formation". Conclusion: In conclusion, central proteins Tp53, MYC, EGFR, AKT1, HDAC1, and SRC can be introduced as a targeted biomarker panel of bioactive peptide treatments. However, extensive research is required to establish this claim before clinical application.

Evaluation of the Cellular Resistance Process in Treated Cells Via Extracorporeal Photopheresis.

Introduction: Extracorporeal photopheresis (ECP) is a therapeutic method applied against some diseases such as cancers. Using 8-methoxypsoralen (8-MOP) and UVA radiation in ECP is associated with achievement in the treatment of patients with leukemic cutaneous T-cell lymphoma (CTCL). Evaluation of cellular resistance versus ECP is the aim of this study. Methods: Data were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed via the GEO2R program. The significant DEGs were assessed via protein-protein interaction (PPI) network analysis by using the STRING database and Cytoscape software. The critical genes were evaluated via gene ontology by using the ClueGO application of Cytoscape software. The identified biological processes were determined and analyzed. Results: Fifty-seven significant DEGs were determined. The main connected component of the PPI network including 32 queried significant DEGs plus 50 first neighbors was constructed. Nineteen histones as critical nodes were assessed via gene ontology, and "nucleosome organization" was pointed out as the crucial biological process. Finally, 15 histones from H2A, H2B, and H3 histone families were identified as the key genes that are involved in the resistance property of the treated cells. Conclusion: In conclusion, 15 members of H2A, H2B, and H3 families (especially H2A family) were considered as the origin of resistance versus ECP treatment. It is concluded that sensitivity to ECP treatment depends on gross molecular events which are involved in the functions of histones.

Network analysis of liver cancer: a system biology approach.

Aim: Determining critical dysregulated proteins in liver cancer was the main aim of this study. Background: Liver cancer is a common health problem characterized by difficulties in early diagnosis and rapid progression. Due to the lack of targeted drugs and the other features of the disease, the survival rate for patients is extremely low. Methods: The related dysregulated proteins for liver cancer were retrieved from the STRING database. The queried proteins were included in a network by Cytoscape software, and the central nodes of the network were enriched via gene ontology. Results: Among 11 introduced central nodes (GAPDH, TP53, EGFR, MYC, INS, ALB, IL6, AKT1, VEGFA, CDH1, and HRAS), HRAS and AKT1 were highlighted as critical dysregulated proteins which can be considered as possible biomarkers. Conclusion: Analysis revealed that AKT1, HRAS and the related biochemical pathways (especially "HIF-1 signaling pathway") are the possible diagnostic and therapeutic agents of liver cancer.

The Clinical Effects of Laser Acupuncture on Hospitalized Patients With Severe COVID-19: A Randomized Clinical Trial.

Introduction: The coronavirus disease (COVID-19) was extended to the entire population in China and around the world, and its mortality rate was about 3.4%. The impact of laser therapy on chronic respiratory diseases has been shown in previous studies. This study was aimed at examining the effects of laser acupuncture (LA) on patients with severe COVID-19. Methods: In the present study, 60 patients with a positive reverse transcription-polymerase chain reaction (RT-PCR) test were assigned to the intervention and control groups (30 patients in each group). The intervention group was treated with LA, that is, laser light with low energy on acupuncture points, once a day for five consecutive days. Results: The participants' mean age in the intervention and control groups was 48.96±12.65 and 53.16±12.28 respectively; 70% of the patients were male and 30% of them were female. IL6 had a significant reduction in the intervention group (P value=0.038) in comparison with the control group (P value=0.535). Furthermore, the mean admission time in the control group was significantly higher than that in the intervention group (P value=0.047). However, the mortality rate in the intervention group was zero, but three patients in the control group died. Conclusion: Our study showed that LA can be used as supportive therapy for routine treatment in patients with severe COVID-19. Moreover, due to LA safety and it's low cost, it could be recommended as an adjuvant to conventional therapy in patients interested in treating their disease with such a method.

Lack of association between Helicobacter pylori infection and biliary tract diseases.

There are ambiguous results about the involvement of Helicobacter species in production of hepatobiliary diseases. This study was aimed to investigate any possible association between the presences of Helicobacter spp., their genotypes and occurrence of different biliary diseases. Cultures of 102 bile samples for Helicobacter spp. did not show any growth, but the presence of Helicobacter genus specific DNA (16s rRNA gene) was detected in 3.92% of them. No significant association was found between development of the diseases and presence of the bacteria. All the Helicobacter genus positive samples belonged to H. pylori species and showed vacA+ (s1/m2), cagA- genotypes.

Elevated interleukin-17A levels despite reduced microRNA-326 gene expression in celiac disease patients under gluten-free diet.

Introduction: The microRNA-326 (miR-326) gene, by targeting ETS Proto-Oncogene 1 (ETS1), regulates the differentiation and interleukin-17A production of T helper 17 (Th17) cells. Celiac disease (CD) is an intestinal autoimmune disorder, in which the cascade of Th17 cells plays an important role in its pathogenicity. The aim of this study was to evaluate the expression changes of miR-326 and its two target genes ETS1 and IL-17A in celiac disease patients under a gluten-free diet (GFD). We expected the expression of miR-326 and IL-17A gene to decrease, and the expression of the ETS1 gene to increase, following the adherence to GFD. Methods: Peripheral blood samples of 40 CD patients under GFD (for more than 1 year) and 40 healthy individuals were collected. RNA was extracted, cDNA was synthesized and the miR-326, ETS1 and IL-17A gene expressions were evaluated by the quantitative polymerase real-time qPCR method. P-value ˂ 0.05 was considered statistically significant. Results: Although miR-326 mRNA expression was significantly lower in CD patients (P = 0.001), no significant difference was observed in ETS1 mRNA level between the two groups (P = 0.54), but IL-17A was significantly overexpressed in CD patients (P=0.002). No significant correlation was observed between the expression of the studied genes and the patients' symptoms and Marsh classification. Conclusion:Adherence to the GFD for one to two years did not have the expected effect on the expression of genes in this panel. The most important finding that contradicted our hypothesis was the observation of high IL-17A levels in CD patients despite dieting, which may be related to the protective effect of this cytokine on intestinal tight junctions, which needs to be confirmed in further studies.

A trend of Medical Negligence in Laser Therapy in the Capital City: A Nine-Year Survey.

Introduction: The purpose of the present study is to investigate the common causes of injuries, claims, and decisions related to laser therapy medical malpractice during a nine-year survey. Methods: The legal documents in the Coroner's Office of Forensic Medicine were investigated in a national database from 2012 to 2020 in Tehran, Iran. The frequency and nature of the cases, including the year of litigation, the location and certificate of the provider, the injury sustained, and the cause of legal action and judgment were collected. Results: Three hundred and eighty-three cases related to injury from laser therapy were registered in the coroner's Office of Forensic Medicine during the study period. The incidence of litigation related to laser surgery showed an increasing trend, with a peak occurrence in 2020. Laser hair removal was the most common (51.2%) litigated procedure. General practice operators (48%) recorded the highest rate of laser-related medical complaints. Lack of skill was the most common reason for failure. Among 383 cases with public decisions, 62.4% of them were fault liability in paid judgment. Conclusion: Medical claims related to laser application are increasing. However, as it is clear, the growth of laser technology and the increasing demand for lasers in medical science require more surveillance to avoid probable injuries and improve patient safety, especially surveillance of the physicians who work outside the scope of their specialty.

Introducing New Potential Biomarkers for Celiac Disease among the Genes Extracted from General Databases.

BACKGROUND: Inflammatory cytokines play roles in the pathogenesis of celiac disease. To introduce new diagnostic markers in patients with celiac disease for easy, fast, low cost, and non-invasive diagnosis, we evaluated the peripheral blood expression levels of interleukin-15 (IL-15), interleukin-17A (IL-17A), interleukin23A (IL-23A), granzyme B (GzmB), T-box transcription factor 21 (TBX21), and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) of patients compared with the healthy controls, which were extracted from public databases organized in a protein-protein interaction network, in this group. METHODS: Peripheral blood mononuclear cells were collected from 30 patients with celiac disease and 30 healthy subjects. Total RNA was extracted, and mRNA expression levels of targeted genes were investigated by the quantitative real-time polymerase chain reaction (PCR) method. SPSS software was used for statistical analysis. Receiver operating characteristic (ROC) curve analysis was performed to characterize the diagnostic ability of the studied genes. RESULTS: The expression of IL-15, IL-17A, IL-23A, GzmB, TBX21, and TNFAIP3 genes in peripheral blood mononuclear cells of patients with celiac disease showed a significant increase compared with the control group. Among them, TNFAIP3, IL23A, and GzmB have better resolution and diagnostic value in differentiating patients with celiac disease from healthy controls. CONCLUSION: Our results suggest that TNFAIP3, IL23A, and GzmB could be useful and sensible markers in differentiating patients with celiac disease from healthy controls. However, the diagnostic relevance of other genes recognized by pathway analysis needs to be further investigated.