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.

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.

Collagen Synthesis as a Prominent Process During the Interval between Two Laser Sessions.

Introduction: Many people suffer from skin photodamage, especially photoaging. The application of a laser to repair damages is a common therapeutic method that is used widely. In the present study, the effectiveness and molecular mechanism of an Er:Glass non-ablative fractional laser on the human skin was assessed via bioinformatics and network analysis. Methods: The gene expression profiles of 17 white female forearm skins which received an Er:Glass non-ablative fractional laser before and after laser treatment in two sessions were extracted from Gene Expression Omnibus (GEO). Data were evaluated via GEO2R and the significant differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis. The central nodes were identified and discussed for the compared set of samples. Results: Five classes of samples were clustered in two categories: first, baseline, 7 and 14 days after the first session of laser treatment, and second, one day after the first laser session, 29 days after the first laser session, and 1 day after the second laser session. The gross cell functions such as cell division and cell cycle and immune response were highlighted as the early affected targets of the laser. Collagen synthesis was resulted after the first laser session. Conclusion: In conclusion, the time interval between laser sessions plays a critical role in the effectiveness of laser therapy. Findings indicate that the gross effect of laser application appears in a short time, and important processes such as collagen synthesis happen later.

The growth inhibitory and apoptotic effects of umbelliprenin in a mouse model of systemic candidiasis.

AIMS: Umbelliprenin has shown promising biological activities, including immunoregulatory, anti-inflammatory, and anti-cancer effects. The present study investigated the growth inhibitory and apoptotic effects of umbelliprenin against Candida albicans in a BALB/c mice model of disseminated candidiasis. METHODS AND RESULTS: First, an antimicrobial assay via microdilution sensitivity test was performed. Then, twenty-five 6-week-old female BALB/c mice (20 ± 12 g) were divided into five groups of five mice, including one control group (no umbelliprenin treatment) and four experimental groups: C. albicans-infected mice treated with umbelliprenin at the doses of 5, 10, 20, and 40 mg kg -1. The brain, lung, kidney, spleen, and liver tissues were examined for fungal infection and histological lesions, and TUNEL staining was performed to assess apoptosis. The ß-1, 3-glucan synthase assay was used to evaluate enzymatic activity, and gene expression analysis was also performed to investigate the transcriptional changes of ERG11, CDR1, ALS1, and HWP1 genes. The MIC of umbelliprenin was 1.5 mg mL-1. Our results showed that at the 40 mg kg -1 dose, umbelliprenin was able to eradicate fungal infection in BALB/c mice. The percentage of apoptotic cells in umbelliprenin-treated groups increased in a concentration-dependent manner. Umbelliprenin (40 mg kg -1) also inhibited the expression of ß-1, 3-glucan synthase, and the genes involved in antifungal resistance (CDR1 and ERG11), as well as the expression of the genes encoding adhesins (ALS1 and HWP1). CONCLUSION: Our results showed that umbelliprenin could promote antifungal effects, partly via inducing apoptosis.

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.

Examining the effect of Helicobacter pylori cagPAI variety on gene expression pattern related to gastric cancer.

OBJECTIVES: We aimed to determine possible association between heterogeneity of Helicobacter pylori cytotoxin-associated gene pathogenicity island and gene expression profiles in patients with distinct histopathological changes. METHODS: Gastric biopsies were obtained from seventy five patients. Microbiological and pathological examinations were done and intactness of Helicobacter pylori cagPAI was determined by PCR using 11 pairs of primers flanking cagζ-cagA regions and cagPAI empty site. Alterations at mRNA levels of eight genes were investigated by real-time PCR and their association with cagPAI intactness and histopathological changes examined statistically. RESULTS: A larger proportion of cagPAI positive strains colonized patients with SAG (52.4%), followed by CG (33.3%), and IM (14.3%). Intact cagPAI was found in 87.5% of the strains obtained from patients with SAG, while significantly lower frequency was detected among those with CG (12.5%) and IM (0%). No significant difference was found among the studied histological groups and fold changes in gene expression of gastric biopsies of Helicobacter pylori infected patients with distinct cagPAI status. However, in each histological group, the strains with more complete gene cluster induced (ErbB2, CCNE1, CTNNB1, and MMP7 in SAG and IM groups) or reduced (TP53, in CG group) expression of the GC associated genes in relatively higher levels. APC, TP53 and E-cadherin were down-regulated in patients with SAG and IM compared with CG patients, irrespective to the status of cagPAI integrity. CONCLUSIONS: Helicobacter pylori strains that carry more complete cagPAI segment could induce remarkably higher levels of mRNA changes of GC associated genes in all histopathological groups.

Extracellular matrix is the main targeted environment in early stage of pancreatic ductal adenocarcinoma.

Aim: Due to weak diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC), detection of PDAC possible biomarkers in early stage is the main aim of this study. Background: PDAC is known as an exocrine cancer with a 5-year overall survival of 11%. Methods: Gene expression profiles of early stage of PDAC tissue and normal tissue are downloaded from gene expression omnibus (GEO) and evaluated via GEO2R. The significant differentially expressed genes (DEGs) are investigated via protein-protein interaction (PPI) network analysis and gene ontology. Results: Among 104 DEGs, ALB, COL1A1, COL1A2, MMP1, POSTN, PLAU, and COL3A1 were pointed out as hub nodes. "Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13" group of 52 biological terms were identified as the main affected terms. Conclusion: In conclusion, ALB, MMP1, and COL1A1 genes were highlighted as possible biomarkers of early stage of PDAC. Dysfunction of extracellular matrix was identified as a main event in patients.

Network Analysis of Effect of Light-Dark Time Ratio on the Gene Expression Profile of Mouse Skin.

Introduction: Circadian rhythms refer to daily cyclic events such as activity and rest in biology. A protein-based core related to the mechanism of circadian is identified. In the present study, the gene expression profiles of mouse skin in different conditions of light-dark times were investigated via protein-protein interaction (PPI) analysis to explore the main affected genes. Methods: GSE174155 was derived from Gene Expression Omnibus (GEO) and was analyzed via GEO2R to find the significant differentially expressed genes (DEGs). The gene expression profiles of Cry-null (genotype: cryptochrome-1(-/-): crytochrome-2 (-/-)) mouse skin versus the wild-type samples in the various circadian times (CTs) were assessed. The queried DEGs plus 50 first neighbors were included in a PPI network via the STRING database by Cytoscape software. The networks were analyzed and the central nodes were evaluated. Results: Three groups of mice based on CTs were identified. 15, 15, and 14 central nodes were determined as central nodes for the analyze networks. There was not a common central node for the analyzed networks. Conclusion: It was pointed out that the light/dark time ratio had a gross effect on the gene expression profile of the skin in the mice. Results imply more investigations to suggest a standard protocol related to CT, considering human lifestyle and exploring suitable protective methods for the jobs which are fixed in the abnormal CT sets.

Introducing BDNF and SNAI1 as the Crucial Targeted Genes by UV Radiation.

Introduction: Due to widespread penetration of UV radiation in human life, the biological effect of UV radiation is studied through many investigations in the field of medicine. There are many assessments about UV radiation which are concerned with protein-protein interaction (PPI) network analysis. In the present study, a network analysis associated with the complementary evaluation of UV radiation on human primary melanocytes is presented. Methods: The gene expression profiles of the irradiated human primary melanocytes and the control cells were extracted from Gene Expression Omnibus (GEO) and were evaluated via PPI network analysis and action map assessment. Results: 69 significant differentially expressed genes (DEGs) were included in the main component of the PPI network. Brain-derived neurotrophic factor (BDNF), SNAI1, and SOCS1 were highlighted as the top dysregulated and hub genes. Results indicate that BDNF and SNAI1 participate in the regulatory unit including the total hubs and top dysregulated genes. Conclusion: Considerable down-regulation of BDNF and up-regulation of SNAI1 as the two critical targeted genes by UV radiation are accompanied by gross alteration in cell functions.

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.

Evaluating of Gene Expression Alteration after Garlic Consumption, Analyzing through Bioinformatics Approach.

Molecular study of garlic as a popular food ingredient could better understand its health benefits such as immunological effects. For this aim, effects of garlic on the spleen and possible side effects including oxidative stress increment, the molecular mechanism is investigated through network analysis of differentially expressed genes in the treatment of garlic. Protein-protein interaction (PPI) network analysis of spleen gene expression profile of Mus musculus (8-week old male C57BL/6J mice) in garlic treatments from a microarray study with the code of GSE10344 was analyzed via GEO2R software. Furthermore, Cytoscape V 3.7.1 was applied to construct and analyze a network of up- and down-regulated genes. The differentially expressed genes (DEGs) were analyzed via the CluePedia plugin of Cytoscape to determine expression patterns. After the identification of central nodes, an action map was created. A total of 77 DEGs were achieved which were including 40 up-regulated and 37 Down-regulated. The centrality analysis of the network indicated that Vcan, Lamb1, and Ltbp1 are hubs and Glra1, Wdr17, Nefl, and Becn1 are bottlenecks. Mutual regulatory connections between hubs and Alb and App (as two non-queried hubs) were determined. The findings indicate that garlic effect on the spleen and its mechanism may be involved mostly with App dysregulation.

Platelet and Haemostasis are the Main Targets in Severe Cases of COVID-19 Infection; a System Biology Study.

INTRODUCTION: Many proteomics-based and bioinformatics-based efforts are made to detect the molecular mechanism of COVID-19 infection. Identification of the main protein targets and pathways of severe cases of COVID-19 infection is the aim of this study. METHODS: Published differentially expressed proteins were screened and the significant proteins were investigated via protein-protein interaction network using Cytoscape software V. 3.7.2 and STRING database. The studied proteins were assessed via action map analysis to determine the relationship between individual proteins using CluePedia. The related biological terms were investigated using ClueGO and the terms were clustered and discussed. RESULTS: Among the 35 queried proteins, six of them (FGA, FGB, FGG, and FGl1 plus TLN1 and THBS1) were identified as critical proteins. A total of 38 biological terms, clustered in 4 groups, were introduced as the affected terms. "Platelet degranulation" and "hereditary factor I deficiency disease" were introduced as the main class of the terms disturbed by COVID-19 virus. CONCLUSION: It can be concluded that platelet damage and disturbed haemostasis could be the main targets in severe cases of coronavirus infection. It is vital to follow patients' condition by examining the introduced critical differentially expressed proteins (DEPs).

Assessment of the Microbiome Role in Skin Protection Against UV Irradiation Via Network Analysis.

Introduction: Diverse microbiotas which have some contributions to gene expression reside in human skin. To identify the protective role of the skin microbiome against UV exposure, proteinprotein interaction (PPI) network analysis is used to assessment gene expression alteration. Methods: A microarray dataset, GEO accession number GSE117359, was considered in this respect. Differential expressed genes (DEGs) in the germ-free (GF) and specific pathogen-free (SPF) groups are analyzed by GEO2R. The top significant DEGs were assigned for network analysis via Cytoscape 3.7.2 and its applications. Results: A total of 28 genes were identified as significant DEGs and the centrality analysis of the network indicated that only one of the seven hub-bottlenecks was from queried genes. The gene ontology analysis of Il6, Cxcl2, Cxcl1, TNF, Il10, Cxcl10, and Mmp9 showed that the crucial genes were highly enriched in the immune system. Conclusion: The skin microbiome plays a significant role in the protection of skin against UV irradiation and the role of TNF and IL6 is prominent in this regard.

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.

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.

Assessment of liver cancer biomarkers.

Liver cancer is the third cause of cancer-related deaths in the world. It is primarily divides into two main types, namely hepatocellular carcinoma (HC) and cholangiocarcinoma (IC). Due to the increasing number of patients with liver cancer and the high mortality rate, early diagnosis of the disease can be helpful in treatment, but most patients are diagnosed atlate stages of HC. The aim of this study is to screen and provide an overview on candidate biomarkers related to primary liver cancer to introduce the critical ones. In this study, various biomarkers related to the diagnosis of primary liver cancer have been studied. Accordingly, biomarkers are divided into different groups as blood biomarkers classified as serum and plasma biomarkers, tissue biomarkers, microRNA biomarkers, proteomic biomarkers and altered genes. Previous researches have focused on liver cells and bile ducts, the surround cellular environment, how cells differentiate, and the types of genes expressed in liver cancer. Some even have focused on the origin of tumor cells and how they differentiate and develop. In all these studies, the expression of specific proteins and genes in liver cancer has been considered. Based on available sources, biomarkers can be considered as candidates to diagnose and prognosis of various types of primary liver cancer, from sources such as blood, tissue, mic-RNA, proteome and genes. However, more investigations are required to introduce a biomarker for precise detection of early liver cancer.

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.

Introducing Transthyretin as a Differentially Expressed Protein in Washing Subtype of Obsessive-Compulsive Disorder.

INTRODUCTION: Obsessive-Compulsive Disorder (OCD) as one of the important mental problems is valuable topic for proteomic research studies to better understand the underlying mechanisms of this disorder. METHODS: In this paper, gel-based proteomic was used to investigate the proteome profile of 16 female patients with OCD, washing subtype before and after treatment with fluoxetine and comparing them with 20 healthy female controls. RESULTS: One of the abnormally expressed protein spots in this study was introduced and examined for protein-protein interaction network analysis via Cytoscape and its plug-ins. Transthyretin (TTR) protein showed significant expression changes (fold change=1.7, P<0.05). While the expression level of TTR is significantly decreased in OCD patients before any treatments, the trend is partially normalized after treatment with fluoxetine in positive responders. Furthermore, TTR interaction profile shows that the proteins interacting with this protein may get affected as this protein expression trend changes in OCD patients. CONCLUSION: TTR can be considered for further studies to be validated as a potential biomarker for OCD.

Fluoxetine Regulates Ig Kappa Chain C Region Expression Levels in the Serum of Obsessive-Compulsive Disorder Patients: A proteomic Approach.

Obsessive-Compulsive Disorder (OCD) is one of the most common mental conditions. Proteome profiling may help identifying important proteins and finally shed lights to complexity of OCD underlying mechanisms. Here, by the application gel-based proteomic approach the proteome profile of patients with washing subtype of OCD before and after treatment with Fluoxetine (positive responders) are compared to healthy matched controls. However, only one of the differentially expressed proteins is examined and introduced in this paper. Proteomic analysis was done by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS)-based. Furthermore, network analysis and biological annotation were handled by Cytoscape Plug-in and CluePedia. The proteome comparison between groups identified protein with the significant expression changes (p<0.05 and fold change ≥ 1.5). While the expression level of Ig Kappa Chain C Region is significantly decreased in OCD patients before any treatments, the trend is almost normalized after treatment with Fluoxetine in positive responders. In addition, interaction profile of IGKC shows that the interacting proteins may be affected as the expression pattern of IGKC changes in OCD patients. In conclusion, IGKC may be introduced as potential biomarker in our study; yet, investigation in bigger sample size and application of validation methods is a requirement.

Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study.

INTRODUCTION: Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD. METHODS: Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software. RESULTS: The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein α-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein α-1-antitrypsin (APOA1) proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process. CONCLUSION: It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential requirements to confirm this preliminary evaluation.