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.

Identification of Targeted Central Genes (IGF1 and HMOX1) by Indirect Cold Physical Plasma in Human Melanocytes.

Introduction: Cold physical plasma is a growing tool in medicine which is applied for the treatment of different cancers. In the present study, the gene profiles of human melanocytes exposed to indirect cold physical plasma versus control individuals are analyzed via protein-protein interaction (PPI) network analysis. Methods: The gene expression profiles were derived from Gene Expression Omnibus (GEO), and the significant differentially expressed genes (DEGs) were decoded via "Expression Atlas". PPI network analysis was applied to find the targeted central genes by indirect cold physical plasma. Results: The main connected component of the constructed network including 74 queried DEGs and 50 added first neighbors was analyzed. Considering degree value, betweenness centrality, closeness centrality, and stress, IGF1 and HMOX1 were introduced as the central nodes. Conclusion: The finding of this study indicates that the down-regulation of IGF1 and the up-regulation of HMOX are the prominent events in response to indirect cold physical plasma treatment at the cellular level. Detection of related biological terms via gene ontology is suggested.

Fibrinogen Dysregulation is a Prominent Process in Fatal Conditions of COVID-19 Infection; a Proteomic Analysis.

INTRODUCTION: Molecular pathophysiology of COVID-19 is not completely known. Expression changes in patients' plasma proteins have revealed new information about the disease. Introducing the key targeted plasma protein in fatal conditions of COVID-19 infection is the aim of this study. METHODS: Significant differentially expressed proteins (DEPs) in the plasma of cases with a fatal condition of COVID-19 were extracted from an original article. These proteins were included in a network via STRING database along with 100 first neighbor proteins to determine central nodes of the network for analyzing. RESULTS: Queried and added proteins were included in a scale free network. Three hub nodes were identified as critical target proteins. The top queried hub proteins were chains of fibrinogen; Fibrinogen Alpha chain (FGA), Fibrinogen gamma chain (FGG), and Fibrinogen beta chain (FGB), which are related to the coagulation process. CONCLUSIONS: It seems that fibrinogen dysregulation has a deep impact on the fatality of COVID-19 infection.

Side effects of omeprazole: a system biology study.

AIM: To assess the effects of omeprazole on the human cardiovascular system is the main aim of this study. BACKGROUND: Omeprazole as a proton pump inhibitor is widely consumed to inhibit gastric acid secretion. METHODS: Gene expression profiles of "human coronary artery endothelial cells" in the absence and presence of omeprazole were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) interacted as an interactome, and the hub nodes are determined. The DEGs were enriched via gene ontology (GO) analysis. The critical hubs were identified based on the GO findings. RESULTS: Among 103 queried DEGs, 61 individuals were included in the main connected component. CTNNB1, HNRNPA1, SRSF4, TRA2A, SFPQ, and RBM5 genes were identified as critical hub genes. Six clusters of biological terms were introduced as deregulated elements in the presence of omeprazole. CONCLUSION: In conclusion, long-term consumption of omeprazole may be accompanied with undesirable effects, however more evidence is required.

Assessment of colon cancer molecular mechanism: a system biology approach.

AIM: The current study aimed to assess and compare colon cancer dysregulated genes from the GEO and STRING databases. BACKGROUND: Colorectal cancer is known as the third most common kind of cancer and the second most important reason for global cancer-related mortality rates. There have been many studies on the molecular mechanism of colon cancer. METHODS: From the STRING database, 100 differentially expressed proteins related to colon cancers were retrieved and analyzed by network analysis. The central nodes of the network were assessed by gene ontology. The findings were compared with a GSE from GEO. RESULTS: Based on data from the STRING database, TP53, EGFR, HRAS, MYC, AKT1, GAPDH, KRAS, ERBB2, PTEN, and VEGFA were identified as central genes. The central nodes were not included in the significant DEGs of the analyzed GSE. CONCLUSION: A combination of different database sources in system biology investigations provides useful information about the studied diseases.

The Principal Role of Several Members of HLA and IRF Genes in Prevention of Oral Mucositis After Chemoradiotherapy.

Introduction: One of the chemoradiotherapy (CRT) side effects is oral mucositis (OM). Since photobiomodulation therapy (PBMT) is a public method for the repair process, in the present study the mechanism of PBMT in the prevention of OM is investigated via the bioinformatics approach. Methods: Six validated and significant differentially expressed genes (DEGs) associated with the prevention of OM in head and neck cancer (HNC) patients who had experienced CRT were extracted from the literature. After adding 50 neighbors from STRING, the network was constructed and analyzed. The results of the action map and network analysis were compared and discussed. Results: HLA gene family were identified as central nodes of the analyzed network. Based on action map finding, activation is prominent action and IRF9 was the potent activator. The role of the IRF gene family was highlighted by action map analysis. Conclusion: Regulation of the immune system by HLA and IRF genes family is a crucial factor in the prevention of OM in the studied patients.

EGR1 Is a Critical Gene in Response of Human Keratinocyte to Blue Light Radiation.

Introduction: Investigating the molecular mechanism of cellular response to light radiation has attracted many researchers' attention. In the present study, the critically affected gene by 7.5 min blue light radiation in human keratinocytes was investigated via network analysis. Methods: Gene expression profiles of human keratinocytes exposed to 7.5 min blue light radiation plus controls were extracted from Gene Expression Omnibus (GEO). The significant dysregulated genes plus 100 first neighbors were investigated by Cytoscape software and its applications. The central nodes of the network based on four centrality parameters were determined and discussed. Results: Among 6 significant dysregulated genes, 4 individuals were recognized by the STRING database. The network was constructed by using the 4 queried genes and 100 first neighbors. EGR1, STAT1, and ISG15 were identified as central nodes; however, the prominent role of EGR1 was highlighted. Conclusion: EGR1 appeared as a critically affected gene after blue light irradiation. It seems that this upregulated gene is responsible for protecting human keratinocytes against stress and cancer. Therefore, the application of blue light may be accompanied by antistress effects in the human body.

Low-Level Laser Therapy: Potential and Complications.

Introduction: Laser therapy has attracted experts' attention in medical sciences. Many benefits of laser therapy are presented besides some complications. In the present study, it is tried to present a new perspective of laser therapy in the various fields of medicine. Methods: Laser therapy-related articles which are combined with regenerative medicine, cosmetic, dentistry, neurodegenerative diseases, kidney, bone fracture, and vaginal function in the English language were searched through the google scholar search engine in the range of 2000-2021. After title screening, the abstracts were evaluated to access the full texts. Results: Basic concepts and various kinds of lasers which are applied in medicine were explained. Applications of laser therapy in various fields of medicine such as pain reduction, wound healing, regenerative medicine, dentistry, and several other body organs were highlighted and some complications were pointed. Conclusion: High potential of laser therapy for application in medicine implies a reconsideration of the laser properties and also styles of laser applications to improve the treatment and prevention of its side effects.

An Investigation of Post-radiation Gene Expression Profiles: A System Biology Study.

Introduction: Genomics and bioinformatics are useful methods for exploring unclear aspects of radiation effects on biological systems. Many radiation-induced alterations in irradiated samples are post-radiation time-dependent. This study aims to evaluate the post-irradiation effects of the gamma ray on human Jurkat cells. Methods: Gene expression profiles of the samples harvested 6 and 24 hours after radiation to find the critical differential expressed genes and the related pathways. Samples are provided from Gene Expression Omnibus (GEO) and analyzed by ClueGO. Results: Twnety-nine critical genes were determined as the important affected genes and 7 classes of related pathways were introduced. CCNE2, PSMD11, CDC25C, ANAPC1, PLK1, AURKA, and CCNB1 that were associated with more than 6 pathways were related to one of the determined pathway groups. Conclusion: Cell protecting pathways were associated with the genes (HSPA5, HSPA8, HSP90B1, HMMR, CEBPB, RXRA, and PSMD11) which were related to the minimum numbers of pathways. The finding of this study corresponds to repair processes which depend on post-radiation time. It seems these sets of genes are suitable candidates for further investigation.

Central Proteins of Plasma in Response to Low-Level Laser Therapy Involve in Body Hemostasis and Wound Repair.

Introduction: Low-level laser therapy (LLLT) is accompanied by protein expression change in the body. There are many efforts to find a clear relationship between the differentially expressed proteins. This study aims to find the central differentiated expressed proteins of plasma after LLLT. Methods: Six proteins are extracted from a proteomics study and the network including these query proteins plus 100 first neighbors was constructed. The central proteins were determined based on degree value, betweenness centrality, closeness centrality (CC), and stress (The centrality parameters). Results: Among 106 nodes of the network, 10 proteins were characterized with the most values of degree, betweenness centrality, CC, and stress. These proteins were determined as central proteins in response to LLLT in plasma. Conclusion: Three query proteins, AHSG, FGG, and SERPINA1, plus 7 first neighbors, namely FGA, ALB, KNG1, FN1, APP, TIMP1, and F5, were identified as central proteins which were dysregulated.

Introducing GATA3 as a prominent player in Crohn's disease.

AIM: This study was aimed at gene assessment of Crohn's disease (CD) through protein-protein interaction (PPI) network analysis to find crucial genes. BACKGROUND: CD is a major subtype of inflammatory bowel diseases (IBD), which affects gastrointestinal tract. PPI network analysis is a suitable tool to clarify a critical gene as a drug target or diagnostic biomarker for these types of diseases. METHODS: Gene expression profile GSE126124 of 20 CD patients and 20 healthy controls was obtained from the Gene Expression Omnibus (GEO) database. RNA profile of peripheral blood mononuclear cells (PBMCs) and colon biopsy samples of the studied groups was investigated. Crucial genes were selected and analyzed via the PPI network by Cytoscape software. Gene ontology enrichment for the hubs, bottlenecks, and hub-bottlenecks was performed via CluGO plugin of Cytoscape software. RESULTS: Eighty-one differentially expressed genes (DEGs) among 250 initial DEGs were highlighted as significant by FC>2 and p-value ≤ 0.05, and 69 significant DEGs were used for PPI network construction. The network was characterized by poor connections, so 20 top neighbors were added to form a scale-free network. The main connected component included 39 query DEGs and 20 added first neighbors. Three clusters of biological processes associated with crucial genes were identified and discussed. CONCLUSION: The results of this study indicated that GATA3 has a key role in CD pathogenesis and could be a possible drug target or diagnostic biomarker for Crohn's disease.

Evaluation of long-term consumption of omeprazole disadvantages: a network analysis.

AIM: Evaluation of deregulated genes after long-term consuming of omeprazole via network analysis. BACKGROUND: Proton pump inhibitors (PPIs) are used to inhibit gastric high rate of acid secretion in patients. Omeprazole as a PPI is a common drug in this regard. Evaluation of long-term consumption of omeprazole is studied in the present study via its effects on the gene expression of "human coronary artery endothelial cells". METHODS: Net effect of the presence of omeprazole on gene expression profiles of "human coronary artery endothelial cells" was evaluated through data from gene expression omnibus (GEO). Results of protein-protein interaction (PPI) network analysis were assessed via biological process examination to find the critical deregulated genes after long-term consumption of omeprazole. RESULTS: "Negative regulation of muscle cell apoptotic process", "negative regulation of DNA binding", "telencephalon cell migration", "forebrain cell migration" "response to cadmium ion", "cell-cell recognition", "positive regulation of protein targeting to mitochondrion", and "central nervous system neuron development" were the clusters of biological processes that were associated to the long -term presence of omeprazole. The final critical deregulated genes were JAK2, PTK2, and NRG1. CONCLUSION: It can be concluded that cell cycle, proliferation, and apoptosis and several essential biological processes are affected and nervous system is a possible target related to the long-term consumption of omeprazole.

Immunological reactions by T cell and regulation of crucial genes in treated celiac disease patients.

AIM: To assess the immunological reactions and gene expression level in the celiac disease (CD) patients under a gluten-free diet (GFD). BACKGROUND: CD is an autoimmune disorder in genetic susceptible individuals and lifelong gluten free diet is the effective treatment method. It seems that treated patients will experience a normal life style though there are documents about some potential damages. METHODS: Gene expression profiles of treated CD patients and healthy samples were obtained from Gene Expression Omnibus (GEO) and compared to find the differentially expressed genes (DEGs). The identified DEGs were introduced in the network and gene ontology (GO) analysis. RESULTS: Ten differentially expressed genes (DEGs) including CCR2, IRF4, FASLG, CCR4, ICOS, TNFSF18, BACH2, LTF, PRM1, and PRM2 were investigated via network analysis. Seven clusters of biological processes (BP) were determined as the affected BP. PThe finding led to introduction of CCR2, IRF4, FASLG, CCR4, and ICOS as the potential immunological markers that are still active despite GFD in the treated CD patients. CONCLUSION: The results of this study indicated that the immune system is already active in treated CD patients despite GFD treatment and exposure to gluten causes potential immunological reactions in these patients.

Highlighted role of VEGFA in follow up of celiac disease.

AIM: Evolution of gene expression change of intestine tissue in celiac patients to find a new molecular prospective of disease is the aim of this study. BACKGROUND: Celiac disease (CD) as an autoimmune disease is known as an immune reaction response to the gluten in patients. It is reported that genetic and environmental conditions are important in onset and progress of CD. METHODS: gene expression profiles of intestinal tissue in 12 celiac patients and 12 healthy controls from gene expression omnibus (GEO) were downloaded and verified by boxplot analysis. The significant and selected differentially expressed genes (DEGs) were included protein-protein interaction (PPI) network analysis. The central nodes were identified by network analyzer. RESULTS: The network was constructed from 161 query DEGs and 50 additional neighbors. GTF2H1, VEGFA, SUMO1, RAD51, MED21, BBP4, LEP, and MAP2K7 as potent hub nodes LRP5, RABGEF1, BCAS2, DYRK1B, AOC3, RABL2A, CRTAP, VEGFA, and SPOPL as potent bottlenecks are introduced as crucial nodes. CONCLUSION: Among the crucial DEGs, Vascular endothelial growth factor A (VEGFA) was highlighted as an important biomarker candidate for follow up of celiac patients.

Gene screening of colorectal cancers via network analysis.

AIM: Identifying crucial genes related to colorectal cancers via protein-protein interaction (PPI) network analysis is the aim of this study. BACKGROUND: colorectal cancer as major reason of mortality is evaluated by genetic and proteomic approaches to find suitable biomarkers. Chromosomal instability plays crucial role in CRC. Expression change of large numbers of genes is reported. METHODS: Differentially expressed genes related to CRCs which obtained from different proteomic methods were extracted from a review article of Paula Álvarez-Chaver et al. The genes interacted by Cytoscape software via STRING database. The central nodes determined and were enriched for biological terms by ClueGO. Action map for central genes was illustrated by CluePedia. The critical genes in CRC were introduced. RESULTS: Among 123 query genes, 114 one recognized by software and were included in the network. SRC, EGFR, PCNA, IL8, CTNNB1, TIMP1, CDH1, and HSPD1 were determined as central genes. After gene ontology analysis SRC, EGFR, and CDH1 were identified as critical genes related to CRC. CONCLUSION: It seems that SRC, EGFR, and CDH1 and the related pathways are possible biomarkers for CRC.

Gene expression profile analysis of colon cancer grade II into grade III transition by using system biology.

AIM: Gene expression profile analysis of colon cancer grade II into grade III transition by using system biology. BACKGROUND: Colon cancer is one of lethal cancer in men and women. Treatment in advanced colon cancer is difficult and survival rate is low. METHODS: Gene expression profiles of children patients with non-preforated appendicitis in comparison with the samples with non- appendicitis abdominal pain are analysis via protein - protein interaction PPI and the critical compounds are introduced by STITCH. RESULTS: Six critical genes including MAPK3, AKT1, SRC, TP53, GAPDH, and ALB were identified as a possible biomarker panel related to colon cancer grade II to III transition. Among these critical genes roles of MAPK3, AKT1, SRC, TP53 are highlighted. CONCLUSION: It was concluded that target therapy to regulate SRC and TP53 may be the effective therapeutic way to treatment of colon cancer and more researches in necessary to design drugs for these purposes.

Introducing Critical Pain-related Genes: A System Biology Approach.

INTRODUCTION: Pain is valuable in diagnosis and also warning of the patients. Many molecular reagents are introduced which are related to pain. In this research, the pain-related genes are screened to identify the critical ones. METHODS: First, the pain-related genes were pulling out from the STRING database, and Cytoscape software was used to make the interactome unit. Then the central genes and their neighbors were analyzed. Finally, the genes were clustered, and the essential genes were introduced. RESULTS: After analyzing 159 genes of the network, FOS, IL6, TNF, TAC1, IL8, and KNG1 were identified as the essential genes. Further analysis revealed that 88 genes are directly connected to the central genes. More resolution led to ignoring TNF and IL8 and considering SCN-alpha and PAICS as additional critical nodes. CONCLUSION: Six critical genes related to pain were identified. They can be potentially considered as new drug targets. Further investigation is required to introduce the central genes as a pain killer.

The critical role of dysregulation of antioxidant activity and carbohydrate metabolism in celiac disease.

AIM: Identification of the important processes and the related genes that are dis-regulated in the celiac disease (CD) was the aim of this study. BACKGROUND: Celiac disease is an autoimmune disorder which is characterized by immune reaction response mostly to wheat gluten. The gluten-free diet is the best-known treatment of the patients. METHODS: Significant differentially expressed proteins (DEPs) related to the CD are extracted from a published proteomics study and are included in protein-protein interaction PPI) network analysis by Cytoscape software and its applications. The central proteins and related processes are identified and discussed. RESULTS: Among 53 queried genes, 51 individuals were recognized by the database, and after network construction, 48 ones included in the network, and three genes remained as isolated nodes. Following 50 neighbors, the network was analyzed, and eight central genes were identified as dis-regulated elements. Related processes and the role of the central genes in celiac are discussed in detail. CONCLUSION: CAT, ENO1, PCK2, ACO2, ALDOOB, GALM, ADA, and ACTBADA as critical genes and Antioxidant activity, carbohydrate metabolism, inflammation, cell growth processes are highlighted as the dis-regulated individuals in CD.

Introducing tumor necrosis factor as a prominent player in celiac disease and type 1 diabetes mellitus.

AIM: This study aimed to screen the common genes between celiac disease (CD) and type 1 diabetes mellitus to find critical ones. BACKGROUND: Celiac disease is a chronic autoimmune disorder which is correlated to type 1 diabetes mellitus (T1DM) in several molecular pathways. Understanding the clear common molecular mechanism of both diseases is of interest to scientists. METHODS: The related genes to the CD and T1DM were obtained from disease query of STRING and included in two separated PPI networks by Cytoscape software version 3.7.1. The networks were analyzed by network analyzer and the hub nodes were determined. The common hubs between the two networks were selected for further analysis and enriched via gene ontology using ClueGO plugin of Cytoscape software. Also, an action map was provided by Cluepedia application of Cytoscape software. RESULTS: Two separated networks of 2000 and 430 genes were constructed related to T1DM and CD, respectively. A total of 84 and 28 hubs were determined for T1DM and CD, respectively. There were 11 common hubs between the two networks. The first top hubs of Type 1 Diabetes Mellitus and CD networks were insulin (INS) and tumor necrosis factor (TNF), respectively. Also, 77 biological terms and pathways (in five clusters) were related to the common hubs. Action map revealed a close relationship between hubs. CONCLUSION: The result of this study indicated that TNF is key mediator of immune reactions in celiac disease and type 1 diabetes mellitus.

Effects of high fat medium conditions on cellular gene expression profile: a network analysis approach.

AIM: This study aimed to evaluate high fat medium (HFM) effect on the gene expression profile of human Sk-hep1 cells and to determine critical differential proteins. BACKGROUND: There is a correlation between high fat diet (HFD), obesity, and non-alcoholic fatty liver disease. Despite wide range of investigations, understanding molecular mechanism of HFD effect on onset and progression of NAFLD warrants further examination. In this study, network analysis is applied to obtain a clear perspective about HFD effects and NAFLD. METHODS: Gene expression profiles of human Sk-hep1 cells treated with HFM versus controls were extracted from GEO. Data were analyzed by GEO2R where the significant and characterized DEGs were included in the PPI network. The top 10 nodes of query DEGs based on four centrality parameters were selected to determine central nodes. The common hub nodes with at least other one central group were identified as central nodes. Action map was provided for the introduced central nodes. RESULTS: Heterogeneous nuclear ribonucleoprotein family including A1, A2/B1, D, R, and D-like, and five proteins (PRPF40A, SRSF1, PCF11, LSM8, and HSP90AA1) were introduced as differential proteins. CONCLUSION: mRNA processing and several biological terms including hypoxia and oxidative stress, apoptosis, regulation of cell morphology and cytoskeletal organization, and differentiation of micro tubes were introduced as dysregulated terms under HFM condition.