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.

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.

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.

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.

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.

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.

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.

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.

Radiation Therapy in Patients With Brain Cancer: Post-proteomics Interpretation.

Introduction: Radiation therapy (RT) as a common method for cancer treatment could result in some side effects. The molecular investigation is one of the approaches that could assist in decrypting the molecular mechanisms of this incident. For this aim, protein-protein interaction (PPI) network analysis as a complementary study of the proteome is conducted to explore the RT effect on brain cancer after the early stage of exposure prior to the appearance of the skin lesion. Methods: Cytoscape 3.7.2 and its plug-ins were used to analyze the network of differential expression of proteins (DEPs) in the treatment condition, and the centrality and pathway enrichment was conducted by the use of NetworkAnalyzer and ClueGO+CluePedia. Results: A network of 15 DEPs indicated that 6 nodes were key players in the network stability and SERPINC1 and F5 were from the query proteins. The pathways of post-translational protein phosphorylation, platelet degranulation, and complement and coagulation cascades were the most highlighted ones for the central nodes that could be affected in RT. Conclusion: The central proteins of the network of early-stage treatments could have additional importance in the mechanisms of radiotherapy response prior to skin lesions. Introduced biomarkers can be used for the patients' follow-up. These candidates are worth precise attention for this type of therapy after approving by validation studies.

The relationship between 174 G/C and -572 G/C of IL-6 gene polymorphisms and susceptibility of celiac disease in the Iranian population.

INTRODUCTION: Celiac disease (CD) is a chronic inflammatory intestinal disorder. Different immunological factors, including inflammatory cytokines, may play an important role in disease susceptibility. AIM: To investigate the relationship between -174G/C and -572G/C gene polymorphisms and the serum level of interleukin 6 (IL-6) and susceptibility to CD in the Iranian population. MATERIAL AND METHODS: In this case-control study blood samples were collected of 105 patients with CD and 106 healthy subjects randomly in 2016 and evaluated by polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. A sequence was also used to confirm the results of both polymorphisms. The IL-6 concentration was measured using ELISA. RESULTS: The results showed a significant relationship between polymorphism -572G in CD patients when compared with control subjects by genotype (p = 0.001) and alleles (p = 0.022), respectively. There was no significant relationship between polymorphism 174G and frequency of genotype, but an association of this polymorphism with the frequency of alleles (p = 0.034), age (p = 0.001), and body mass index (p = 0.003) was seen. The serum level of interleukin-6 was significantly associated only with rs1800796 (p < 0.001). CONCLUSIONS: The results confirm previous studies in different parts of the world and indicate that IL-6 (572G/C) polymorphism may play a role in susceptibility to CD in the Iranian population.

Celiac disease microarray analysis based on System Biology Approach.

AIM: Aim of this study is screen of the large numbers of related genes of CD to find the key ones. BACKGROUND: Celiac disease (CD) is known as a gluten sensitive and immune system dependent disease. There are several high throughput investigations about CD but it is necessary to clarify new molecular aspects mechanism of celiac. METHODS: Whole-genome profile (RNA) of the human peripheral blood mononuclear cells (PBMCs) as Gene expression profile GSE113469 was retrieved Gene Expression Omnibus (GEO) database. The significant genes were selected and analyzed via protein-protein interaction (PPI) network by Cytoscape software. The key genes were introduced and enriched via ClueGO to find the related biochemical pathways. RESULTS: Among 250 significant genes 47 genes with expressed change above 2 fold change (FC) were interacted and the constructed network were analyzed. The network characterized by poor connections so it was promoted by addition 50 related nodes and 18 crucial nodes were introduced. Two clusters of biochemical pathways were identified and discussed. CONCLUSION: There is an obvious conflict between microarray finding and the well-known related genes of CD. This problem can be solve by more attention to the interpretation of PPI ntwork analysis results.

Network analysis of common genes related to esophageal, gastric, and colon cancers.

AIM: The aim of this study was to provide a biomarker panel for esophageal, gastric and colorectal cancers. It can help introducing some diagnostic biomarkers for these diseases. BACKGROUND: Gastrointestinal cancers (GICs) including esophageal, gastric and colorectal cancers are the most common cancers in the world which are usually diagnosed in the final stages and due to heterogeneity of these diseases, the treatments usually are not successful. For this reason, many studies have been conducted to discover predictive biomarkers. METHODS: In the present study, 507 genes related to esophageal, gastric and colon cancers were extracted.. The network was constructed by Cytoscape software (version 3.4.0). Then a main component of the network was analyzed considering centrality parameters including degree, betweenness, closeness and stress. Three clusters of the protein network accompanied with their seed nodes were determined by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO) analysis of the key genes in combination to the seed nodes was performed. RESULTS: The network of 17 common differential expressed genes in three esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges were constructed. Eight crucial genes were determined. Three Clusters of the network were analyzed by GO analysis. CONCLUSION: The analyses of common genes of the three cancers showed that there are some common crucial genes including TP53, EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to gastrointestinal cancers and can be predictive biomarkers for these cancers.

The early efficacy of Heller myotomy in the treatment of Iranian patients with achalasia.

AIM: The purpose of this study was to determine the efficacy of Heller myotomy for the treatment of achalasia in a referral center in Tehran, and investigate the clinical characteristics, manometric results and treatment responses among three achalasia subtypes in Iranian patients. BACKGROUND: Esophageal achalasia is an unusual swallowing disorder, characterized by high pressure in the lower esophageal sphincter (LES) on swallowing, failure relaxation of the LES and the absence of peristalsis in esophageal. PATIENTS AND METHODS: In this cross sectional study, clinical symptom and esophageal manometry before and 2 months after treating with Heller myotomy in 20 patients with achalasia who were referred to Taleghani Hospital, Tehran, in 2013 were evaluated. Patients' demographic, clinical features and response to treatment were analyzed using SPSS software (version 20, Chicago, IL, USA). RESULTS: All the diagnostic criteria measured after the treatment were significantly different (P<0.05) before and after the therapy. The average decline in the length of the esophagus was 1.8 cm and dysphasia score was 7.25 units. Also an average decline in LES Resting Pressure, LES Residual Pressure, PIP, and IRP were 23.2 mmHg, 14.3 mmHg, 3.4 mmHg and 17.8 mmHg, respectively. CONCLUSION: Results of this study showed that the Heller myotomy is highly effective in relieving dysphasia in patients with achalasia. Also, type II achalasia is the most common subtype of achalasia with a better response to Heller myotomy compared to the other types.

Angiotensin converting enzyme insertion/deletion (I/D) (rs4646994) and Vegf polymorphism (+405G/C; rs2010963) in type II diabetic patients: Association with the risk of coronary artery disease.

HYPOTHESIS: Little is known about the concomitant presence of the angiotensin-converting enzyme (ACE) (rs4646994) D allele and vascular endothelial growth factor(VEGF) (+405G/C; rs2010963) G allele on the susceptibility of coronary artery disease (CAD). Here we examined the hypothesis that ACE-D and VEGF-G alleles act synergistically to increase the severity of CAD in patients with type II diabetes mellitus (T2DM). MATERIALS AND METHODS: The VEGF (rs2010963) and ACE (rs4646994) genotypes were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and PCR, respectively in 510 T2DM patients undergoing their first coronary angiography. Diabetic patients were classified as T2DM patients with and without CAD (control). RESULTS: The crude odds ratio (OR) for the presence of CAD in ID+DD and D allele carriers were 1.98 (p=0.01) and 1.55 (p=0.001), respectively. Also, adjusted ORs in the presence of normolipidemia and the absence of history of hypertension for the risk of CAD in the either ACE(rs4646994) D allele or VGEF(rs2010963)-G alleles were 2.08 (p=0.004) and 1.75 (p=0.024), respectively. In addition, the concomitant presence of the ACE-D and VEGF-G alleles increased the risk of CAD 2.25-fold (p=0.043). CONCLUSION: Our results indicated that ACE(rs4646994)-D allele alone and in the presence of VEGF(rs2010963)-G allele can be an important independent risk factor for susceptibility of CAD in T2DM patients even after correcting for conventional risk factors in a population of Iran.

Expression of Glucose Transporter 4 (GLUT4) is Increased by Cinnamaldehyde in C2C12 Mouse Muscle Cells.

BACKGROUND: In diabetes mellitus because of the absence or insufficient sensitivity to insulin, glucose transporter protein in cell membrane, glucose transporter 4, is decreased. GLUT4 is the major glucose transporter in skeletal muscle and adipose tissue, which is under control of insulin. It remains, however, unclear whether cinnamaldehyde plays a regulatory role(s) or not. OBJECTIVES: The objective of this study was to investigate the effects of cinnamaldehyde on GLUT4 gene expression. MATERIALS AND METHODS: This study was an experimental trial. Tests were performed in triplicates. This study examined effects of cinnamaldehyde on Glut4 gene expression in C2C12 skeletal muscle cells by using Real Time PCR. C2C12 myoblasts were cultured in DMEM + 10 % FBS. After differentiation of myoblasts to myotubes, the cells were serum deprived for 5 hours and then treated with 10, 20, or 50 µM of cinnamaldehyde for 1 hour. RESULTS: Our data revealed a significant increase in the expression of Glut4 in cinnamaldehyde treated cells. In addition, GLUT4 mRNA level was increased in a dose dependent manner. Analyses were performed using the SPSS 16 for Windows software. Differences between the groups were determined by one-way ANOVA. CONCLUSIONS: These results demonstrate that cinnamaldehyde up regulates the expression of mouse skeletal muscle GLUT4 gene expression.

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.