Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

BACKGROUND: Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. METHODS: Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. RESULTS: CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). CONCLUSION: The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for 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.

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.

Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.

In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity. These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers. It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.

Classification and Diagnostic Prediction of Colorectal Cancer Mortality Based on Machine Learning Algorithms: A Multicenter National Study.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. This study aimed to predict survival outcomes of CRC patients using machine learning (ML) methods. MATERIAL AND METHODS: A retrospective analysis included 1853 CRC patients admitted to three prominent tertiary hospitals in Iran from October 2006 to July 2019. Six ML methods, namely logistic regression (LR), Naïve Bayes (NB), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (DT), and Light Gradient Boosting Machine (LGBM), were developed with 10-fold cross-validation. Feature selection employed the Random Forest method based on mean decrease GINI criteria. Model performance was assessed using Area Under the Curve (AUC). RESULTS: Time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type emerged as crucial predictors of survival based on mean decrease GINI. The NB (AUC = 0.70, 95% Confidence Interval [CI] 0.65-0.75) and LGBM (AUC = 0.70, 95% CI 0.65-0.75) models achieved the highest predictive AUC values for CRC patient survival. CONCLUSIONS: This study highlights the significance of variables including time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type in predicting CRC survival. The NB model exhibited optimal efficacy in mortality prediction, maintaining a balanced sensitivity and specificity. Policy recommendations encompass early diagnosis and treatment initiation for CRC patients, improved data collection through digital health records and standardized protocols, support for predictive analytics integration in clinical decisions, and the inclusion of identified prognostic variables in treatment guidelines to enhance patient outcomes.

Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study.

Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.

Human-Induced Pluripotent Stem Cell‒Derived Keratinocytes, as Therapeutic Option in Vitiligo.

Vitiligo is a skin condition affecting 1% of the global population, causing non-scaly, chalky-white macules on the skin and hair. It is caused by the pathologic destruction of melanocytes, which produce melanin. Research has focused on the abnormalities of melanocytes and their interaction with neighboring keratinocytes. Current treatments are mainly immunosuppressive drugs and UV radiation, which are scarce and ineffective. To treat vitiligo, regenerative medicine techniques, such as cell-based and cell-free methods, are recommended. Keratinocyte cell transplantation has shown promising results in treating vitiligo. Moreover, studies suggest individualized therapy for diseases can be provided by reprogramming somatic cells into induced pluripotent stem cells. On the other hand, differentiation into particular cell types is a key component of induced pluripotent stem cells-based treatment. In this chapter, the differentiation and validation of human induced pluripotent stem cells into a keratinocyte as a therapeutic option in vitiligo will be discussed.

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.

Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

Assessment of the Response of Human Umbilical Vein Endothelial Cells to Photodynamic Therapy: Highlighting the Role of Il-17 Signaling Pathway.

Introduction: Photodynamic therapy (PDT) is a method based on the application of a photosensitive agent and the administration of light irradiation on the treated samples. PDT is applied as an effective tool with minimal side effects against tumor tissues. This study aimed to assess the targets of critical genes by PDT at the cellular level of cancer to provide a new perspective on its molecular mechanism. Methods: To assess the effect of PDT, we extracted the differentially expressed genes (DEGs) from the gene expression profiles of human umbilical vein endothelial cells (HUVECs) treated with PDT from Gene Expression Omnibus (GEO) databases. The queried DEGs were evaluated via a regulatory network and gene ontology enrichment to find the critical targets. Results: Among 76 queried significant DEGs, 27 individuals were interacted by activation, inhibition, and co-expression actions. Thirty DEGs were related to the five classes of biological terms. The IL-17 signaling pathway and PTGS2, CXCL8, FOS, JUN, CXCL1, ZFP36, and FOSB were identified as the crucial targets of PDT. Conclusion: PDT as a stimulator of gene expression and an activator of gene activity overexpressed and hyper-activated many genes. It seems that PDT introduces a number of genes and pathways that can be regulated by anticancer drugs to fight against cancers.

Efficacy Evaluation of Human Skin Treatment with Photodynamic Therapy in Actinic Keratoses Patients.

Introduction: Photodynamic therapy (PDT) is a combined method of light and light-activated chemicals that are called photosensitizers (PSs). PDT is recommended as a high cure rate method with fewer side effects and a noninvasive tool to treat cancer. This study aimed to evaluate PDT efficacy as a therapeutic method against actinic keratoses in patients via protein-protein interaction (PPI) network analysis by using the gene expression profiles of Gene Expression Omnibus (GEO). Methods: Twenty-one gene expression profiles were extracted from GEO and analyzed by GEO2R to determine the significant differentially expressed genes (DEGs). The significant DEGs were included in PPI networks via Cytoscape software. The networks were analyzed by the "Network Analyzer", and the elements of the main connected components were assessed. Results: There were three main connected components for the compared sets of the gene expression profiles including the lesional region of skin before (Before set) and after (After set) PDT versus healthy (healthy set) skin and before versus after. The before-health comparison showed a partial similarity with the After-Healthy assessment. The before-after evaluation indicated that there were not considerable differences between the gene expression profile of the lesional region before and after PDT. Conclusion: In conclusion, PDT was unable to return the gene expression pattern of the actinic keratoses skin to a healthy condition completely.

Laser Diode - GaAlAs Acupuncture in the Treatment of Central Obesity: a Randomized Clinical Trial.

Background: : Obesity is a global health challenge. Traditional approaches, including increased physical activity, dietary interventions, and medical therapy, often yield limited success, propelling some patients toward costly and invasive procedures like bariatric surgery. Laser acupuncture has been suggested as a complementary therapeutic approach to overcome this challenge. The present study investigated the effectiveness of laser acupuncture treatment in weight loss and abdominal subcutaneous fat reduction. Methods: : A randomized, blinded, sham-controlled clinical trial was conducted, with 30 subjects each in the intervention and control groups. Patients in the intervention group underwent 12 sessions of laser acupuncture treatment within a month (three sessions/week), whereas those in the control group received sham laser treatment on identical acupoints. The patients were instructed not to alter their physical activity levels or dietary regimens. All parameters were evaluated before and after the treatment. Results: : Significant reductions in weight, body mass index, and waist circumference were noted in both intervention and control groups. Further analysis revealed a more significant decrease in the laser acupuncture group. Abdominal sonography revealed a marked decrease in periumbilical fat thickness in the intervention group. Conversely, laboratory evaluations showed no significant difference between the two groups. Conclusion: : Laser acupuncture is an effective method for weight loss in patients with periumbilical abdominal fat. The observed impact on subcutaneous fat suggests its potential as a non-invasive intervention for individuals seeking weight management alternatives. Further research is warranted to validate these findings and explore the underlying mechanisms of laser acupuncture in adipose tissue modulation.

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.

Assessment of Photosensitizer Concentration Effects on the Efficacy of Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) is an attractive approach in medicine. Due to its noninvasive nature and low side effects, PDT has been developed quickly. In the present study, the gene expression profiles of the human cell line that was treated via PDT in the sub-lethal concentration (LC50) and super-lethal concentration (LC90) of a photosensitizer (PS) from Gene Expression Omnibus (GEO) were extracted and the common differentially expressed genes (DEGs) were investigated. Methods: The gene expression profiles of the treated cells were compared with a control, and the common DEGs were determined. The common DEGs were assessed via protein-protein interaction (PPI) network analysis, and gene ontology enrichment was evaluated. The related biological terms for the common genes were identified. Results: Ninety-four common DEGs were selected to be analyzed. It appeared that the activation and increment of gene expression were prominent processes. Jun, Dusp1, Atf4, and Atf3 as four critical genes were highlighted. "Chromosomal and microsatellite instability in colorectal cancer" was identified as the main class of biological terms related to the assessed DEGs. Conclusion: The major molecular events which happened in both analyses indicated that PDT, independent from the concentration of PS, induced gross molecular changes such as the upregulation of Jun and Dusp1.

DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.

Stem cells, as a group of undifferentiated cells, are enriched with self-renewal and high proliferative capacity, which have attracted the attention of many researchers as a promising approach in the treatment of many diseases over the past years. However, from the cellular and molecular point of view, the DNA repair system is one of the biggest challenges in achieving therapeutic goals through stem cell technology. DNA repair mechanisms are an advantage for stem cells that are constantly multiplying to deal with various types of DNA damage. However, this mechanism can be considered a trump card in the game of cell survival and treatment resistance in cancer stem cells, which can hinder the curability of various types of cancer. Therefore, getting a deep insight into the DNA repair system can bring researchers one step closer to achieving major therapeutic goals. The remarkable thing about the DNA repair system is that this system is not only under the control of genetic factors, but also under the control of epigenetic factors. Therefore, it is necessary to investigate the role of the DNA repair system in maintaining the survival of cancer stem cells from both aspects.

GMP-Based Isolation of Full-Term Human Placenta-Derived NK Cells for CAR-NK Cell Therapy in Malignant Melanoma.

Melanoma, a severe type of skin cancer, poses significant management challenges due to its resistance to available treatments. Despite this obstacle, the high immunogenicity of melanoma renders it amenable to immune therapy, and NK cells have been identified as possessing anti-tumor properties in immunotherapy. The development of chimeric antigen receptor (CAR)-modified NK cells, or CAR-NK cells, has shown potential in enhancing immunotherapeutic regimens. To achieve this, researchers have explored various sources of NK cells, including those derived from the placenta, which offers benefits compared to other sources due to their limited ex vivo expansion potential. Recent studies have indicated the capacity to expand functional NK cells from placenta-derived cells in vitro that possess anti-tumor cytolytic properties. This chapter discusses the isolation of full-term human placenta-derived NK cells using Good Manufacturing Practice-based methods for CAR-NK cell therapy in melanoma.

Introducing Critical Genes in Response to Photodynamic Therapy: A Network Analysis.

Introduction: Photodynamic therapy (PDT) is applied as an efficient method for preventing the progress of cancers. Light and a photosensitive compound which is known as photosensitizer (PS) are the main parts of PDT. In the present study, molecular events after using PDT in the presence of a super lethal dose of a PS were assessed via protein-protein interaction (PPI) analysis. Methods: Data were extracted from Gene Expression Omnibus (GEO). The gene expression profiles of the treated human Sk-Cha1 cells via PDT were compared with the control cells. Expressed change analysis and PPI network analysis were administrated via Cytoscape software v 3.7.2 to find the critical differentially expressed genes (DEGs). Regulatory relationships between the central DEGs were evaluated and the highlighted genes were identified. Results: The significant amounts of gene expression values were grouped and a few DEGs characterized by tremendously expressed values were identified. EGFR, CANX, HSPA5, MYC, JUN, ITGB1, APP, and CDH1 were highlighted as hub-bottleneck DEGs. EGFR, CDH1, and JUN appeared as a set of SEGs, which play a crucial role in response to PDT in the treated Sk-Cha1 cells. Conclusion: In conclusion, regulatory relationships between EGFR, CDH1, and JUN, which have an effect on the regulation of cellular survival, differentiation, and proliferation, were highlighted in the present investigation.

Long and Short-terms Effects of Ablative Fractional Laser Therapy on Human Skin: A Network Analysis.

Introduction: Time-dependent effects of laser radiation have been investigated by researchers. An understanding of the molecular mechanism of the time course effect of the laser needs molecular assessment and function evaluation of the related genes. In the present study, the importance of repetition of treatment after 4 weeks and gene expression alteration after 7 days of laser radiation versus one day on the human skin was evaluated via protein-protein interaction (PPI) network analysis and gene ontology enrichment. Methods: The differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus (GEO) and assessed via PPI network analysis. The critical DEGs were enriched via gene ontology. The related biological processes and biochemical pathways were retrieved from "GO-Biological process" and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) respectively. Results: The repetition of laser therapy after 4 weeks of the first treatment did not have a significant effect on treatment efficacy. Sixty-three significant DEGs and six classes of biological terms discriminated the samples seven days after the treatment from individuals one day after the treatment. The studied DEGs were organized into two clusters with certain functions. Conclusion: Based on the findings after laser therapy, several days are required to complete the critical processes such as DNA biosynthesis and skin cornification.

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.

Gene Ontology Assessment of Indirect Cold Physical Plasma and UV-Radiation Molecular Mechanism at the Cellular Level.

Introduction: The development of therapeutic methods implies an understanding of the molecular mechanism of the applied methods. Due to the widespread use of UV radiation and cold physical plasma in medicine, the molecular mechanism of these two methods is compared via gene ontology. Methods: Data were derived from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) which discriminate the cells treated with UV radiation versus indirect cold physical plasma were analyzed via gen ontology enrichment. The related biochemical pathways were extracted from the "Kyoto Encyclopedia of Genes and Genomes" (KEGG). Results: Among the 152 queried DEGs, 18 critical genes including SOC1, LDLR, ALO5, PTGS2, TNF, JUNB, TNFRSF1A, CD40, SMAD7, ID1, SMAD6, SERPINE1, PMAIP1, MDM2, CREB5, GADD45A, E2F3, and ETV5 were highlighted as the genes that victimize the two methods. Conclusion: NOTCH1 and TNF as the main genes plus SEREPINE1, KLF, and BDNF were introduced as the significant genes that are involved in the processes which discriminate cold physical plasma administration and UV-radiation as the two evaluated therapeutic methods.