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.

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.

Screening of Altered Metabolites and Metabolic Pathways in Celiac Disease Using NMR Spectroscopy.

BACKGROUND: Celiac disease (CeD) is an autoimmune intestinal disorder caused by gluten protein consumption in genetically predisposed individuals. As biopsy sampling is an invasive procedure, finding novel noninvasive serological markers for screening of at-risk CeD population is a priority. Metabolomics is helpful in monitoring metabolite changes in body fluids and tissues. In the present study, we evaluated serum metabolite levels of CeD patients relative to healthy controls with the aim of introducing new biomarkers for population screening. METHOD: We compared the serum metabolic profile of CeD patients (n = 42) and healthy controls (n = 22) using NMR spectroscopy and multivariate analysis. RESULT: 25 metabolites were identified by serum metabolic profiling. Levels of 3-hydroxyisobutyric acid and isobutyrate showed significant differences in CeD patients' samples compared with healthy controls (p < 0.05). According to pathway analysis, our data demonstrated that changes in nine metabolic pathways were significantly disrupted/affected in patients with CeD. These enriched pathways are involved in aminoacyl-tRNA biosynthesis; primary bile acid biosynthesis; nitrogen metabolism; glutamine and glutamate metabolism; valine, leucine, and isoleucine biosynthesis and degradation; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis. CONCLUSION: In summary, our results demonstrated that changes in the serum level of 25 metabolites may be useful in distinguishing CeD patients from healthy controls, which have the potential to be considered candidate biomarkers of CeD.

Evaluation of Laser Effects on the Human Body After Laser Therapy.

Lasers have wide applications in the treatment and diagnosis of diseases and various medical fields. Laser therapy like the other methods has advantages and disadvantages. Some risks such as bleeding, pain, and infection are created after laser therapy. Explanation and evaluation of laser effects on cell function, tissue, and the body are the aims of this study. We reviewed papers available from 1986 to 2019 about the effects of lasers on cells and tissue. An online search of PubMed, Science Direct and Google scholar using such keywords as "laser", "cell", "tissue", "body" and "side effects" was performed. The laser photons are absorbed by chromophores, resulting in the target heating and localized damage. Laser irradiation alters cellular metabolism and cellular functions. These alterations may be accompanied by undesired side effects which can be monitored via metabolites level change in the body. Based on this finding, laser therapy may be associated with several side effects and complications; therefore, before treatment, the determination of laser types and their properties is necessary to avoid creating side effects. The advantages and disadvantages of the treatment type should be considered in order to choose the best treatment with the least side effects. The patients' awareness of possible side effects before treatment and also an effective follow-up and management of patients after action are two important points in laser therapy. Training curriculum definition should be determined for laser applicant qualifications in different medical fields.

Evaluation of expression of common genes in the intestine and peripheral blood mononuclear cells (PBMC) associated with celiac disease.

AIM: this study was conducted to investigate expression of the genes associated with CD in the target tissue in order to estimate contribution of each single gene to development of immune response. Then, the same set of genes was evaluated in peripheral blood mononuclear cells (PBMCs). BACKGROUND: Celiac disease (CD) is a chronic systemic autoimmune disease of the small intestine occurring in genetically-susceptible individuals. There are several genes related to immune response. METHODS: For this purpose, the genes related to CD were extracted from public databases (documents of proteomics and microarray-based techniques) and were organized in a protein-protein interaction network using the search tool for retrieval of interacting genes/proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were introduced and enriched via ClueGO to find the related biochemical pathways. The network was analyzed, and the most important genes were introduced based on central indices. RESULTS: Among 20 CD genes as hub and bottleneck nodes, there were 7 genes with common expression in blood and intestinal tissue (C-X-C motif chemokine 11(CXCL11), granzyme B (GZMB), interleukin 15(IL-15), interleukin 17(IL-17A), interleukin 23(IL-23A), t-box transcription factor 21(TBX21), and tumor necrosis factor alpha-induced protein 3(TNFAIP3)). CONCLUSION: The enriched biological process related to the central nodes of celiac network indicated that most of hub-bottleneck genes are the well-known ones involved in different types of autoimmune and inflammatory diseases.

Evaluation of CXCR1 as a possible diagnostic biomarker in acute appendicitis.

AIM: The present study was conducted to determine the genes with common expression in blood and appendix tissue samples in order to introduce them as possible diagnostic biomarkers. BACKGROUND: Diagnosis of acute appendicitis (AA) without applying computed tomographytomography (CT), subjecting the patient to significant radiation, can be surprisingly difficult. Blood circulation may have conscious alterations in its RNA, protein, or metabolite composition. METHODS: The genes related to appendix tissue and blood samples of the patients with AA were extracted from public databases. Fold change (FC) ≥ 2 in blood and FC ≥ 5 in appendix tissue samples were considered to screen differentially expressed genes (DEGs). A protein-protein interaction network was organized using the search tool for retrieval of interacting genes and proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were enriched by DAVID Bioinformatics Resources to find the related biochemical pathways. RESULTS: Among the DEGs in blood and appendix tissue samples, C-X-C motif chemokine receptor 1(CXCR1), leukocyte immunoglobulin-like receptor A3 (LILRA3), low-affinity immunoglobulin gamma Fc region receptor III (FCGR3), and superoxide dismutase 2(SOD2) were common in both sources. CXCR1 was found as only hub gene upregulated in both blood and tissue of the patients with AA compared to controls and those with other abdominal pain. CONCLUSION: CXCR1, FCGR3, LILRA3, and SOD2 were determined as a suitable possible biomarker panel for diagnosis of AA disease.

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.

Pharmaceutical Advances and Proteomics Researches.

Proteomics enables understanding the composition, structure, function and interactions of the entire protein complement of a cell, a tissue, or an organism under exactly defined conditions. Some factors such as stress or drug effects will change the protein pattern and cause the present or absence of a protein or gradual variation in abundances. The aim of this study is to explore relationship between proteomics application and drug discovery. "proteomics", "Application", and "pharmacology were the main keywords that were searched in PubMed (PubMed Central), Web of Science, and Google Scholar. The titles that were stablished by 2019, were studied and after study of the appreciated abstracts, the full texts of the 118 favor documents were extracted. Changes in the proteome provide a snapshot of the cell activities and physiological processes. Proteomics shows the observed protein changes to the causal effects and generate a complete three-dimensional map of the cell indicating their exact location. Proteomics is used in different biological fields and is applied in medicine, agriculture, food microbiology, industry, and pharmacy and drug discovery. Biomarker discovery, follow up of drug effect on the patients, and in vitro and in vivo proteomic investigation about the drug treated subjects implies close relationship between proteomics advances and application and drug discovery and development. This review overviews and summarizes the applications of proteomics especially in pharmacology and drug discovery.

The Evaluation of Laser Application in Surgery: A Review Article.

There are several types of surgeries which use lasers in the operating room. Surgeons use lasers in general surgery or surgical specialties to cut, coagulate, and remove tissue. In modern medicine, the application of laser therapy is an attractive subject due to its minimal invasive effect. Today lasers are widely used in the treatment and diagnosis of many diseases such as various cancers, lithotripsy, ophthalmology, as well as dermatology and beauty procedures. Depending on the type of lasers, the wavelength and the delivery system, most lasers have replaced conventional surgical instruments for better wound healing results. Over time, by using many different tools and devices, new lasers have been created; as a result, they are used in a wide range of medical special cases. In this review, laser applications in surgery and its beneficial effects compared to previous surgeries with the aim of providing appropriate therapeutic and non-invasive solutions with minimal side effects after surgery are investigated.

Comparison of cytokine and gene activities in tissue and blood samples of patients with celiac disease.

AIM: The aim of this study is to explore the expression of genes associated to celiac disease (CD) in the target tissue and peripheral blood monocytes (PBMC) or serum to introduce possible potential biomarkers. BACKGROUND: Celiac disease (CD) is an autoimmune disease induced by gluten ingestion in genetically predisposed individuals. Despite technological progress, small intestine biopsy is still the gold standard for diagnosis of CD. METHODS: CD data were collected from public databases (proteomics and microarray-based techniques documents). Differentially expressed genes (DEGs) in PBMC or serum as well as small intestinal biopsies from celiac patients compared to normal were collected and analyzed to introduce common individuals. Gene ontology was done to identify the involved biological terms. RESULTS: Among 598 CD genes in biopsies and 260 genes in PBMC or serum, 32 common genes with a similar expression pattern in both sources were identified. A total of 48 biological terms were introduced which were involved in the CD via the determined DEGs. "Cytokine activity" was the most expanded one of the biological terms. CONCLUSION: In this analysis, it was concluded that 32 potential biomarkers of CD can be assessed by complementary research to introduce effective and available biomarkers in biopsy and blood.

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.

Human Urine Proteomics: Analytical Techniques and Clinical Applications in Renal Diseases.

Urine has been in the center of attention among scientists of clinical proteomics in the past decade, because it is valuable source of proteins and peptides with a relative stable composition and easy to collect in large and repeated quantities with a noninvasive procedure. In this review, we discuss technical aspects of urinary proteomics in detail, including sample preparation, proteomic technologies, and their advantage and disadvantages. Several recent experiments are presented which applied urinary proteome for biomarker discovery in renal diseases including diabetic nephropathy, immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis, lupus nephritis, membranous nephropathy, and acute kidney injury. In addition, several available databases in urinary proteomics are also briefly introduced.