Reduced frequency of circulating regulatory T cells and their related immunosuppressive mediators in treated celiac patients.

BACKGROUND: Regulatory T cells (Tregs) have an important role in the control of the immune responses. This study aimed to compare the frequency of peripheral blood (PB) CD4+ CD25+ FoxP3+ Treg cells and PB and duodenal expression levels of pro- and anti-inflammatory mediators in treated celiac disease (CD) patients and healthy controls. METHODS AND RESULTS: Duodenal biopsy specimens and PB samples were collected from 60 treated CD patients and 60 controls. Flow cytometry analysis was conducted on peripheral blood mononuclear cell (PBMC) specimens and relative PB and duodenal mRNA expression levels of CD25, forkhead box P3 (Foxp3), interleukin (IL)-10 and granzyme B (GrzB) were evaluated using quantitative real-time PCR. The levels of serum IL-10 and IL-6 were tested with sandwich enzyme-linked immunosorbent assay kits. p values < 0.05 were considered significant. Flow cytometry analysis showed a significant decrease in the number of Tregs in CD patients' PBMC specimens (p = 0.012). CD25 and Foxp3 PB mRNA expressions were also lower in CD patients without reaching the significance level (p > 0.05). IL-10 PB mRNA and protein expression did not differ between the groups (p > 0.05), and GrzB PB expression was significantly reduced in CD patients (p = 0.001). In duodenal specimens of CD patients, while significantly increased CD25, Foxp3 mRNA expression (p = 0.01 and 0.001, respectively) and decreased IL-10 mRNA expression (p = 0.02) were observed, GrzB mRNA expression did not differ between groups (p > 0.05). Moreover, a high serum level of IL-6 was observed in CD patients (p = 0.001). CONCLUSIONS: Despite following the gluten free diet, there may still be residual inflammation in the intestine of CD patients. Accordingly, finding a therapeutic approach based on strengthening the function of Treg cells in CD might be helpful.

Serum pro-inflammatory and anti-inflammatory cytokines and the pathogenesis of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS) is characterized by demyelination, infiltration of inflammatory cells into the nervous system and dysregulation of serum inflammatory cytokines. We investigated the correlation of serum cytokines and other inflammatory markers with the EAE pathogenesis. After EAE induction, the levels of different serum cytokine/inflammatory mediators were measured. Furthermore, motor functions, myelination, and lymphocyte infiltration in EAE mice were also assessed. Our results revealed that the serum concentrations of T-helper 1 (Th1) and Th17 cytokines, interleukin (IL)-6, IL-1ß, IL-1α and prostaglandin E2 in EAE mice were significantly higher than controls. The ratios of pro- to anti-inflammatory cytokines were different between the EAE and the control group. A statistically significant positive correlation was found between the IL-6/IL-10 ratio and the EAE severity, demyelination rate, and lymphocyte infiltration in EAE mice. Results indicate that the profiles of serum pro- and anti-inflammatory cytokines might be useful as biomarkers for monitoring the pathological manifestation of EAE. Furthermore, evaluating the dynamic interplay of serum cytokine levels and the correlation with pathogenic mechanisms of EAE may provide diagnostic and therapeutic insights for MS and some other inflammatory disorders.

Lack of association between cyclooxygenase 2-765G/C gene polymorphism and breast cancer risk in Ahvaz, west-south Iran.

Cyclooxygenases are key enzymes in conversion of arachidonic acid into prostaglandin H2. Cyclooxygenase-2 (COX-2) increases prostaglandins in neoplastic tissue. COX-2 has important roles in cell proliferation cancers, angiogenesis, and alzheimer. COX-2 is up-regulated in several types of cancer, and it is hypothesized that COX-2 expression may be genetically influenced. Our main objective was to evaluated the association of polymorphism COX-2 with risk of breast cancer in khouzestan province, and the second objective of the study was to evaluate the association with biochemistry parameters. This study consisting of 150 patients with breast cancer and 120 normal DNA was extracted from the white blood cells. Polymorphism cox2 gene was detected by polymerase chain reaction according to the standard methods. The profile lipids and estrogen were measured in two groups by standard methods. Chi square analysis showed that there was no association between breast cancer risk and COX-2 -765G>C genotype and alleles. Also, no association were observed between -765G>C polymorphism and biochemistry parameters. A multiple logistic regression model with cox2 genotypes and LDL and HDL as covariates revealed that there is no significant association between cox2 genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer.

Immunomodulatory and Anti-Inflammatory Effects of Vitamin A and Tryptophan on Monocyte-Derived Dendritic Cells Stimulated with Gliadin in Celiac Disease Patients.

Celiac Disease (CeD) is an autoimmune disorder with various symptoms upon gluten exposure. Dendritic cells (DCs) play a crucial role in gliadin-induced inflammation. Vitamin A (retinol; Ret) and its metabolite, retinoic acid (RA), along with tryptophan (Trp) and its metabolite, kynurenic acid (KYNA), are known to influence the immune function of DCs and enhance their tolerogenicity. This research aims to assess the impact of gliadin on DC maturation and the potential of vitamin A and tryptophan to induce immune tolerance in DCs. The monocyte cells obtained from peripheral blood mononuclear cells (PBMCs) of celiac disease patients were differentiated into DCs in the absence or presence of Ret, RA, Trp, KYNA, and then stimulated with peptic and tryptic (PT) digested of gliadin. We used flow cytometry to analyze CD11c, CD14, HLA-DR, CD83, CD86, and CD103 expression. ELISA was carried out to measure TGF-ß, IL-10, IL-12, and TNF-α levels. qRT-PCR was used to assess the mRNA expression of retinaldehyde dehydrogenase 2 (RALDH2) and integrin αE (CD103). The mRNA and protein levels of Indoleamine 2, 3-dioxygenase (IDO) was analyzed by qRT-PCR and Western blot assays, respectively. Our findings demonstrate that PT-gliadin enhances the expression of maturation markers, i.e. CD83, CD86 and HLA-DR and promote the secretion of TNF-α and IL-12 in DCs. Interestingly, vitamin A, tryptophan, and their metabolites increase the expression of CD103, while limiting the expression of HLA-DR, CD83, and CD86. They also enhance RALDH2 and IDO expression and promote the secretion of TGF-ß and IL-10, while limiting IL-12 and TNF-α secretion. These findings suggest that vitamin A and tryptophan have beneficial effects on PT-gliadin-stimulated DCs, highlighting their potential as therapeutic agents for celiac disease. However, further research is needed to fully understand their underlying mechanisms of action in these cells.

Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients.

Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFß in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFß (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.

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.

The role of vascular endothelial growth factor +405 G/C polymorphism and albuminuria in patients with type 2 diabetes mellitus.

Observations on the association between the vascular endothelial growth factor (VEGF) gene polymorphism and nephropathy have been inconsistent, which might be due to ethnic and geographical variations. Furthermore, the relationship between +405 G/C polymorphism and albuminuria in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between +405 G/C polymorphism and albuminuria in an population from Tehran of Iran. A total of 255 consecutive patients with type 2 diabetes and microalbuminuria (Group A) and 235 patients with type 2 diabetes and normoalbuminuria (Group B) were included. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to detect the VEGF alleles. In univariate analysis, the groups were statistically similar in all variables except for HbA1c (8.53 ± 1.7 in Group A vs. 8.2 ± 1.73 in Group B; P = 0.034), 24-h urinary albumin (201.33 ± 84.8 in Group A vs. 22.88 ± 3.5 in Group B; P < 0.001), and the frequency of GG genotype (31% in Group A vs. 18.7% in Group B; P = 0.006). The GG genotype was the independent predictor of albuminuria [P = 0.014, OR = 1.771, 95% confidence interval (CI) = 1.124-2.790]. Our study showed that the G allele was not associated with albuminuria, but the GG genotype in the VEGF gene is independently associated with development of nephropathy in the our diabetic population.

Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes.

The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22-0.68); P = 0.001]. Similar findings were not observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32-0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13-0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276G>T SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.

A common variant in the adiponectin gene and polycystic ovary syndrome risk.

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 "TT" genotype compared with "TG and GG" genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20-3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03-2.86). Furthermore, the ADIPOQ rs2241766 "T" allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18-2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 "TT" genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.

Vascular endothelial growth factor (VEGF) +405 C/G polymorphism is associated with essential hypertension in a population from Tehran of Iran.

Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction-restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy-Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44-4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200-2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.

The -4817 G>A (rs2238136) variant of the vitamin D receptor gene: a probable risk factor for colorectal cancer.

Vitamin D appears to have anti-tumor activities in the large bowel. Our aim was to investigate whether -4817 G>A (rs2238136) polymorphism located at 5'-untranslated region (5'-UTR) of the human vitamin D receptor (VDR) gene was associated with colorectal cancer (CRC) risk. We conducted a case-control study and VDR genotypes, determined by Bpu10I restriction endonuclease digestion of PCR-amplified DNA, were performed on 327 cases with CRC and 327 controls. The distribution of VDR -4817 G>A genotypes and alleles differed significantly between cases with CRC and controls even after adjustment for confounding factors such as age, BMI, sex, and smoking status. Individuals carrying the "AA" genotype had a 2.09-fold increased risk compared with those with "GG" genotype (P = 0.016, OR = 2.09, 95% CI = 1.15-3.78) and a 1.87-fold increased risk compared with those with "GG and GA" genotypes (P = 0.033, OR = 1.87, 95% CI = 1.05-3.33) for CRC. Furthermore, the VDR "A" allele was significantly overrepresented in cases with CRC than controls (P = 0.044; OR = 1.28, 95% CI = 1.01-1.63). Interestingly, the analysis of the SNP revealed that all these associations were stronger for women subjects than for all subjects combined. These data indicated for the first time a direct association between "AA" genotype of VDR gene -4817 G>A polymorphism and CRC, with a stronger association for female subjects. However, our findings remain to be confirmed in other populations.

Association of plasma leptin levels and insulin resistance in diabetic women: a cross-sectional analysis in an Iranian population with different results in men and women.

OBJECTIVES: The objective of this study was to assess the association of serum leptin levels with insulin resistance (IR), metabolic syndrome (MetS), lipid levels, and glucose control in an Iranian type 2 diabetic population. FINDINGS: In this cross-sectional analysis, 132 type 2 diabetic patients (79 women) and 71 healthy non-diabetic and non-hypertensive individuals (40 women; as control subjects) were included. Homeostasis model assessment (HOMA) of insulin values ≥ 1.8 for females and 1.7 for males was regarded as the cut-point of IR. MetS was defined according to updated 2005 NCEP ATP III criteria. The leptin correlated with HOMA-IR values without adjustment (r = 0.24; p < 0.005) and with adjustment for sex and diabetes (r = 0.44; p < 0.005). Sex had significant effect on the BMI adjusted association of HOMA-IR (quintiles) and leptin (df = 4 F(12.7) = 3.5; p = 0.011). In diabetic women (but not men), leptin levels were different between those with and without IR (27.3 ± 1.9 vs. 18.2 ± 3.3; p < 0.05). BMI adjusted leptin values were different between subjects with and without MetS (22.2 ± 1.7 vs.14.8 ± 1.2; p < 0.001). No association was noticed between BMI-adjusted leptin with glycated hemoglobin or blood lipid levels. CONCLUSIONS: In this study, plasma leptin concentration correlated with IR independent of the effect of obesity in female but not male diabetic subjects.

Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome.

PURPOSE: The purpose of this study was to evaluate the associations between polymorphisms in vitamin D receptor (VDR), parathyroid hormone (PTH), calcium sensing receptor (CASR), insulin receptor (INSR), and adiponectin (ADIPOQ) genes and biochemical characteristics of women with polycystic ovary syndrome (PCOS). METHODS: Serum levels of LH, FSH, estradiol, testosterone, prolactin, SHBG, glucose, IGF-1, IGFBP-1, calcium, phosphorus, PTH, 25(OH)D, and 1,25(OH)(2) D were measured in 56 women with PCOS. Furthermore, genotyping five, one, one, two, and two polymorphisms of the VDR, PTH, CASR, INSR, and ADIPOQ genes, respectively, were performed. RESULTS: The VDR TaqI "CC" genotype was associated with elevated serum levels of LH (p = 0.011). There were significant associations between decreased levels of SHBG and both VDR BsmI "GG" (p = 0.009) and ADIPOQ BsmI "CC" (p = 0.016) genotypes. Furthermore, patients with CaSR Hin1I "TG" genotype showed higher HoMA-IR (p = 0.008). All these associations remained significant after Bonferroni correction. In addition, phosphorus correlated negatively with estradiol (r = -0.298, P = 0.026) and positively with glucose (r = 0.287, P = 0.032). CONCLUSIONS: These data indicated for the first time that it is possible that the VDR and CASR gene variants through their effects on LH and SHBG levels, and insulin resistance are involved in pathogenesis of PCOS.

Papillary Thyroid Cancer-Promoting Activities of Combined Oral Contraceptive Components.

BACKGROUND: Thyroid cancer is more common in women at reproductive age, suggesting the relationship between its high-incidence and therapeutic use of hormonal medications, such as oral contraceptives (OCPs). The aim of this study was to identify the effect of low-dose combined OCP (LD-COC) on proliferation, apoptosis, and migration of human papillary thyroid cancer (PTC) BCPAP cell line. MATERIALS AND METHODS: BCPAP cells were cultured and treated with the combination of 90nM levonorgestrel (LNG) and 20nM ethinylestradiol (EE) for 48 hours. Afterward, using 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay, the proliferation of the cells was measured. Apoptosis was determined by using a Caspase-3 ELISA kit. Migratory properties of combined LNG and EE were studied through wound scratch assay. The expression levels of pro-apoptotic factor BAX, anti-apoptotic factor Bcl2, and proliferation marker Ki67 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: Upon treatment with the combination of LNG and EE, proliferation and migration of BCPAP cells were significantly enhanced. However, LNG and EE remarkably inhibited apoptosis of these cells. Furthermore, treating PTC cells with combined LNG and EE caused a marked increase in the expression of Bcl2 and Ki67 and a considerable decrease in BAX levels (P˂0.05). CONCLUSION: Our data linked the use of COCs and the progression and aggressiveness of PTC, suggesting the role of these hormonal compounds as promoting factors for PTC tumors. Despite these observations, further investigations will be required to fully establish the pathogenic impact of these medications on PTC.

Role of Flt4 in Skin Protection against UVB Radiation: A System Biology Approach.

Background: Although the application of ultraviolet B (UVB) in phototherapy of human skin is a common therapeutic method, it is known as a risk factor for skin cancer. This study aims to assess the role of differentially expressed genes (DEGs) to find the critical one that is mainly responsible for skin protection against UVB radiation. Methods: The gene expression profiles of irradiated mice by UVB that issued skin protection against exposure are extracted from Gene Expression Omnibus (GEO) and analyzed by GEO2R. The significant DEGs are assessed via gene ontology (GO) analysis and the critical individuals are investigated via action mapping. Results: Thirty-eight significant DEGs that provide skin resistance against UVB irradiation were determined. Among the query DEGs, 26 individuals were related to 43 biological terms. Flt4, F3, Tspan6, Cblb, and Itgb6 were highlighted as the critical DEGs to promote skin protection against UVB irradiation. Conclusion: The finding indicates that Flt4 is the key DEG that is mainly responsible for protecting skin from UVB exposure.

Gene Activation as a Cell Protection Mechanism Against Gamma-Ray radiation.

Introduction: Gamma radiation is accompanied by prominent biological effects and damages. Cell proliferation and tumorigenesis are highlighted as the main resulted effects of gamma radiation on cultured cells. This study aims to assess the dysregulated mode of gene function after gamma radiation in human Jurkat cells. Methods: Six gene expression profiles from Gene Expression Omnibus (GEO) were analyzed by GEO2R to find the significant differentially expressed genes (DEGs) via gamma radiation. Action map analysis was applied to screen the query DEGs. Results: Among 108 study genes, 20 critical DEGs including AURKA, AURKB, BORA, CCNB1, CCNB2, CCNF, CDC20, CDCA8, CENPA, CENPE, CENPF, KIF18A, KIF20A, KIF23, BUB1, DLGAP5, ECT2, PLK1, SGO2, and TPX2 were introduced as down-regulated genes by the gamma ray. Conclusion: Activators of the introduced critical genes may be the cell protector against gamma radiation.

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.

Suppressive Mechanisms Induced by Tregs in Celiac Disease

Celiac disease (CD) is a systemic immune-mediated disorder caused by the dietary gluten in individuals who are genetically susceptible to the disease. In fact, CD is a T cell-mediated immune disease in which gluten-derived peptides activate the lamina propria CD4+ Teff cells, and these T-cell subsets can cause the intestinal tissue damages. Also, there are additional subsets of CD4+ T cells with suppressor functions. These subsets express the master transcription factor, FOXP3, and include Tr1 cells and CD4+CD25+ regulatory T cells (Tregs), which are the main population involved in maintaining the peripheral tolerance, preventing the autoimmune diseases and limiting the chronic inflammatory diseases such as CD. The suppressive function of Tregs is important to maintain the immune homeostasis. This paper examined the features and the basic mechanisms used by Tregs to mediate the suppression in CD.