De novo antioxidant peptide design via machine learning and DFT studies.

Antioxidant peptides (AOPs) are highly valued in food and pharmaceutical industries due to their significant role in human function. This study introduces a novel approach to identifying robust AOPs using a deep generative model based on sequence representation. Through filtration with a deep-learning classification model and subsequent clustering via the Butina cluster algorithm, twelve peptides (GP1-GP12) with potential antioxidant capacity were predicted. Density functional theory (DFT) calculations guided the selection of six peptides for synthesis and biological experiments. Molecular orbital representations revealed that the HOMO for these peptides is primarily localized on the indole segment, underscoring its pivotal role in antioxidant activity. All six synthesized peptides exhibited antioxidant activity in the DPPH assay, while the hydroxyl radical test showed suboptimal results. A hemolysis assay confirmed the non-hemolytic nature of the generated peptides. Additionally, an in silico investigation explored the potential inhibitory interaction between the peptides and the Keap1 protein. Analysis revealed that ligands GP3, GP4, and GP12 induced significant structural changes in proteins, affecting their stability and flexibility. These findings highlight the capability of machine learning approaches in generating novel antioxidant peptides.

Proteome analysis, bioinformatic prediction and experimental evidence revealed immune response down-regulation function for serum-starved human fibroblasts.

Emerging evidence indicates that fibroblasts play pivotal roles in immunoregulation by producing various proteins under health and disease states. In the present study, for the first time, we compared the proteomes of serum-starved human skin fibroblasts and peripheral blood mononuclear cells (PBMCs) using Nano-LC-ESI-tandem mass spectrometry. This analysis contributes to a better understanding of the underlying molecular mechanisms of chronic inflammation and cancer, which are intrinsically accompanied by growth factor deficiency.The proteomes of starved fibroblasts and PBMCs consisted of 307 and 294 proteins, respectively, which are involved in lymphocyte migration, complement activation, inflammation, acute phase response, and immune regulation. Starved fibroblasts predominantly produced extracellular matrix-related proteins such as collagen/collagenase, while PBMCs produced focal adhesion-related proteins like beta-parvin and vinculin which are involved in lymphocyte migration. PBMCs produced a more diverse set of inflammatory molecules like heat shock proteins, while fibroblasts produced human leukocytes antigen-G and -E that are known as main immunomodulatory molecules. Fifty-four proteins were commonly found in both proteomes, including serum albumin, amyloid-beta, heat shock cognate 71 kDa, and complement C3. GeneMANIA bioinformatic tool predicted 418 functions for PBMCs, including reactive oxygen species metabolic processes and 241 functions for starved fibroblasts such as antigen processing and presentation including non-classical MHC -Ib pathway, and negative regulation of the immune response. Protein-protein interactions network analysis indicated the immunosuppressive function for starved fibroblasts-derived human leucocytes antigen-G and -E. Moreover, in an in vitro model of allogeneic transplantation, the immunosuppressive activity of starved fibroblasts was experimentally documented. Conclusion: Under serum starvation-induced metabolic stress, both PBMCs and fibroblasts produced molecules like heat shock proteins and amyloid-beta, which can have pathogenic roles in auto-inflammatory diseases such as rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus, aging, and cancer. However, starved fibroblasts showed immunosuppressive activity in an in vitro model of allogeneic transplantation, suggesting their potential to modify such adverse reactions by down-regulating the immune system.

Body composition and serum levels of matrix metalloproteinase-9, adiponectin and AMP-activated protein kinase in breast cancer survivors.

Background: Available data suggest that obesity is related to changes in the several adipocyte-derived proteins levels, which are involved in cancer recurrence. The purpose of this work was to investigate the correlation between obesity with metalloproteinase-9 (MMP-9), adiponectin and adiponectin and AMP-activated protein kinase (AMPK) levels by comparing serum levels of MMP-9, AMPK in normal weight and obese breast cancer survivors. Materials and Methods: In this cross-sectional study, 30 normal weight breast cancer survivors (body mass index [BMI] 18.5-25 kg/m2) and 30 obese breast cancer survivors (BMI ≥30 kg/m2) were investigated. Anthropometric parameters and serum levels of MMP-9, adiponectin, and AMPK were compared between the two groups. Results: No differences were detected in the serum levels of MMP-9, adiponectin, and AMPK in obese patients and normal weight patients (P > 0.05). There were no correlations between MMP-9, adiponectin, and AMPK levels with anthropometric measurements in two groups (P > 0.05). Conclusion: We found that there was a lack of correlation between obesity measures and serum levels of MMP-9, adiponectin, and AMPK. In breast cancer survivors, it seems that circulating levels of adiponectin, AMPK, and MMP-9 do not change in obesity state.

Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor via reduction in angiogenesis and alternations in Gch1 and Spr expressions.

Introduction: The microenvironment of solid tumors such as breast cancer is heterogeneous and complex, containing different types of cell, namely, cancer stem cells and immune cells. We previously reported the immunoregulatory behavior of the human immune cell in a solid tumor microenvironment-like culture under serum starvation stress for 96 h. Here, we examined the effect of this culture-derived solution on breast cancer development in rats. Method: Ninety-six-hour starved PBMCs supernatant (96 h-SPS) was collected after culturing human PBMCs for 96 h under serum starvation condition. Breast cancer stem cells, LA7 cell line, was used for in vitro study by analyzing gene expression status and performing cytotoxicity, proliferation, scratch wound healing assays, followed by in vivo tumor induction in three groups of mature female Sprague Dawley rats. Animals were treated with 96 h-SPS or RPMI and normal saline as control, n = 6 for each group. After biochemical analysis of iron, lactate, and pH levels in the dissected tumors, Ki67 antigen expression, angiogenesis, and necrosis evaluation were carried out. Metabolic-related gene expression was assessed using RT-qPCR. Moreover, 96 h-SPS composition was discovered by Nano-LC-ESI-MS/MS. Results: 96 h-SPS solution reduced the LA7 cell viability, proliferation, and migration and Gch1 and Spr genes expression in vitro (p< 0.05), whereas stemness gene Oct4 was upregulated (p< 0.01). The intracellular lactate was significantly decreased in the 96 h-SPS treated group (p = 0.007). In this group, Gch1 and Spr were significantly downregulated (p< 0.05), whereas the Sox2 and Oct4 expression was not changed significantly. The number of vessels and mitosis (Ki67+ cells) in the 96 h-SPS-treated group was significantly reduced (p = 0.024). The increased rate of necrosis in this group was statistically significant (p = 0.04). Last, proteomics analysis revealed candidate effectors' components of 96 h-SPS solution. Conclusion: 96 h-SPS solution may help to prevent cancer stem cell mediated tumor development. This phenomenon could be mediated through direct cytotoxic effects, inhibition of cell proliferation and migration in association with reduction in Gch1 and Spr genes expression, angiogenesis and mitosis rate, and necrosis augmentation. The preliminary data obtained from the present study need to be investigated on a larger scale and can be used as a pilot for further studies on the biology of cancer development.

Downregulation of Stemness Genes and Induction of Necrosis in Rat LA7 Cancer Stem Cells Induced Tumors Treated with Starved Fibroblasts Culture Supernatant.

BACKGROUND: Stem cell differentiation therapy is a promising strategy in cancer treatment. we show that protein cocktail prepared from serum starved fibroblasts has therapeutic potential based on this strategy. METHODS: The condition medium was prepared from foreskin isolated fibroblasts and analyzed by Liquid chromatography electrospray ionization mass spectrometry-mass spectrometry (LC-ESI-MS/MS). LA7 mammary gland cancer stem cells originated tumors were induced in Sprague Dawley rats. The rats treated subcutaneously with DMEM (group A), condition medium (group B), or normal saline (group C) once daily for 7 days. Then the tumors were removed and divided into the two parts, one part was used to quantify gene expression by stem-loop RT-qPCR assay and the other part was used for Hematoxylin & Eosin (H & E), Giemsa, and immunohistochemistry (IHC) staining. RESULTS: All induced tumors appeared as sarcomatoid carcinoma (SC). Immunohistochemistry staining confirmed this conclusion by recognizing the tumor as Ki67+, cytokeratin+, vimentine+, and estrogen receptor negative SC. RT-qPCR analysis revealed that Oct4-, Sox-2, Nanog- gene expression was much reduced in the condition medium treated tumors versus proper controls (p< 0.05). Tissue necrosis was more prevalent in this group while tumors volume was diminished almost by 40%. The LC-ESI-MS/MS analysis unrevealed the stemness reducing and the cell death inducing proteins such as, pigment epithelium-derived factor (PEDF), insulin like growth factor binding protein-5 (IGFBP-5) and -7 (IGFBP-7) in the condition medium. CONCLUSION: This study showed that the substances released from starved human fibroblasts were able to down-regulate the stemness-related genes and induce necrosis in LA7 derived tumors.

Evaluation of the Level of Salivary sHLA-G in Children Aged 3-5 Years with or without Dental Caries.

METHODS AND MATERIALS: This analytic cross-sectional study was carried out on 83 healthy children aged 3 to 5 years of both genders, who were divided into three groups based on decayed dental surfaces (ds): group 1, caries-free children (CF, n = 29); group 2, children with 1 ≤ ds ≤ 3, 1 ≤ ds ≤ 4, and 1 ≤ ds ≤ 5 for age 3, 4, and 5 years, respectively (ECC, n = 20); and group 3, children with ds ≥ 4, ds ≥ 5, and ds ≥ 6 for age 3, 4, and 5 years, respectively (S-ECC, n = 34). The unstimulated saliva samples were collected, and the salivary sHLA-G concentration was measured by the ELISA kit. The SPSS Statistics v17.0 software and Mann-Whitney, Kruskal-Wallis, chi-square, and Spearman's rank correlation tests were used for statistical analysis. The level of significance was considered at p < 0.05. RESULTS: The mean concentrations of salivary sHLA-G in CF, ECC, and S-ECC groups were 3.18 ± 2.28, 5.64 ± 5.51, and 6.21 ± 6.03 ng/l, respectively (p = 0.047), and the mean salivary sHLA-G level was comparatively higher in children with dental caries than that of the CF group (p = 0.02), but there is no significant difference between ECC and S-ECC groups (p > 0.05). Spearman's rank correlation test showed a weak positive correlation (p = 0.039, r = 0.22), between the level of salivary sHLA-G and dental caries. CONCLUSION: The present study provides some preliminary evidences on relationship between sHLA-G and dental caries in children.

Systemic effects of starved fibroblast culture supernatant on immunosuppressed rats treated with cancer stem cells (LA7).

BACKGROUND: The present study aimed to investigate and compare the effect of starved fibroblast culture supernatant (SFS), DMEM and normal saline alone or along with LA7 on dexamethasone-treated immunosuppressed Wistar rats. METHODS: After the isolation of fibroblasts from the fresh foreskin of children, it was cultured in serum-free DMEM, and the supernatant collected after 16 hours (16h-SFS). This solution and the other treatments were injected subcutaneously into the rats from each group once daily for 14 days. The liver, intestine and lung histology along with blood cellular and biochemical characteristics were studied. RESULTS: The results showed that dexamethasone as immunosuppressant reduced the body weight. The histological change in the liver was mild fibrosis induced by LA7+16h-SFS. Also, among the different blood cellular and biochemical indices measured, the eosinophil percentage in the 16h-SFS treated rats , glucose levels in the 16h-SFS+LA7 group and triglyceride concentrations in the 16h-SFS group were changed (p<0.05). CONCLUSION: This study showed that the secretions of starved fibroblasts especially that combined with LA7 cancer stem cells could induce some minor histological and biochemical changes in immunosuppressed rats, and also it opened a new window for subsequent investigations on unknown mechanisms related to this work.

Comparison of women's stress in unexplained early pregnancy loss and normal vaginal delivery.

BACKGROUND: Postpartum period and recurrent abortion are stressful conditions that affect women's mental health. Stress and depression lead to the release of stress biomarkers that may be dangerous for the mother and fetus. The aim of this study was to determine stress in the after recurrent pregnancy loss (RPL) and normal vaginal delivery (NVD) in the north of Iran. MATERIALS AND METHODS: This case-control study was done on forty women with NVD and forty women with RPL. Stress was measured through measuring serum cortisol, Perceived Stress Scale-14 (PSS-14), and the revised version of the Symptom Checklist-90 (SCL-90-R). Data were analyzed using the Statistical Package for the Social Sciences (SPSS) 22.0 software. Chi-square test, independent-samples t-test, Mann-Whitney U-test, and Pearson correlation were used to analyze the data. RESULTS: Findings showed that nonpregnant healthy women had significantly higher cortisol level than RPL women (mean ± standard deviation [SD]: 155.80 ± 84.97 ng/ml and 126.02 ± 50.44 ng/ml, P < 0.011), respectively. Furthermore, they had higher PSS-14 and SCL-90 scores than PRL women (mean ± SD: 25.87 ± 7.48 and 25.5 ± 9.19, P = 0.745, and mean ± SD: 1.27±0.63 and 1.20 ± 0.53, P = 0.624), respectively. CONCLUSIONS: High levels of cortisol reflect the acute stress caused by the care of the baby in women. Therefore, social support for the pregnant woman by the health-care team is an essential factor for reducing postpartum depression.

Appraisal of the characteristic dataset of the synthesized nanobiocomposite hydrogel.

The survey on the characteristic data presented here, are related to the study entitled "Transparent chitosan based nanobiocomposite hydrogel: Synthesis, thermophysical characterization, cell adhesion and viability assay" [1]. Scanning electron microscopy images, evidence for structural confirmation and more description about biological assay are presented. The thermophysical characteristic including Differential scanning calorimetery and thermogravimetery analysis are described. Swelling kinetic parameters for the prepared hydrogel were calculated and showed that Schott's equation is well suited for explaining the swelling behavior of this transparent hydrogel.

Targeting LA7 breast cancer stem cells of rat through repressing the genes of stemness-related transcription factors using three different biological fluids.

Down-regulation of stemness genes expression is important in differentiation therapy against cancer stem cells (CSCs). The aim of this study was to evaluate the Oct4 , Sox2, Nanog, and C-myc expression in rat breast cancer stem cells (LA7) which treated with human ovarian follicular fluid (FF), replicative senescent fibroblast culture supernatant (P14), and 16 h serum starved fibroblast supernatant (16 h-SFS). The cells were exposed to these biological fluids for 24 h, 72 h, and 7 days. Stem-loop RT-qPCR assay was used to quantify the expression of above mentioned genes. Results showed that FF had the least cytotoxic effect on the LA7 cells. Except for Nanog gene, exposure of LA7 cell line to 16 h-SFS and P14 decreased significantly expression of the three other genes after 24 h (P < 0.05). Nanog and Sox2 genes expression was also decreased in LA7 cells which have been already treated with FF for 24 h. Moreover, compared to the control solution, the expression of Oct4 increased significantly after 7 days exposure to FF (P < 0.05). Annexin V-PE /7-AAD-, acridine orange/ethidium bromide staining and doubling time assays revealed apoptosis and necrosis induction by these biological fluids in LA7 cells. Moreover, in an in vitro model of metastasis assay, i.e., scratch test, these fluids exhibited anti-LA7 migration activity which culminated in 16 h-SFS treated cells. Generally, this study showed that FF, 16 h-SFS, and P14 have positive effects on down-regulation of Nanog, Oct4, Sox2 and C-myc expression, and consequently can increase the differentiation of breast cancer stem cells. For the first time, this study provided some evidence indicating that some biological fluids have potential to differentiate the CSCs, show anti- survival, growth-, and cell migration activity.

Transparent chitosan based nanobiocomposite hydrogel: Synthesis, thermophysical characterization, cell adhesion and viability assay.

This study designed to explore the characteristic features of the novel prepared hydrogel. This transparent nanocomposite hydrogel was formulated with employing environmental friendly biopolymer, "chitosan". To increase the hydrophilicity of chitosan, it was quaternized with triethyl amine. Also by incorporating click protocol, the triazole rings were inserted in the structure. After decoration with appropriate chemicals using efficient methods, functionalized chitosan and the corresponding hydrogel were investigated by Fourier transform infrared (FT-IR), thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC) and dynamic-mechanical thermal analysis (DMTA). Swelling behavior of the synthesized hydrogel was assayed in both room temperature and 37 °C. Moreover, swelling kinetics were appraised and found that the experimental data fit the Schott's equation. To study the cell adhesion and proliferation, MTT assay was performed and the SEM images of 24, 48 and 72 h of direct cell culture on the surface of the scaffold were obtained. Morphological features of cultured cells were confirmed with Giemsa staining. The results displayed the potential capability of the synthesized scaffold for being used in bioapplications.

Psychological distress in women with recurrent spontaneous abortion: A case-control study.

OBJECTIVE: The aim of the present study was to evaluate psychological problems in women with recurrent spontaneous abortion (RSA). MATERIALS AND METHODS: In this case-control study, 115 women with RSA were assigned to the case group and 240 non-pregnant women comprised the control group. The revised version of the Symptom Checklist-90 (SCL-90-R) and the Intolerance of Uncertainty scale (IUS) were used for assessing mental health problems. RESULTS: The results showed that the mean Global Severity Index (GSI) of the SCL-90-R and the IUS scores in the case and control groups were 109.10±59.85 and 68.91±22.17, and 82.98±52.99 and 59.19±23.01, respectively. GSI was the strongest predictor of RSA [odds ratio (OR)=6.43; 95% confidence interval (CI): 3.52-11.72]. The chance estimate of RSA was approximately 2.1 times higher in women in rural areas (OR=2.07; 95% CI: 1.16-3.69), and 2 times higher at 12 months after the last pregnancy (OR=1.99; 95% CI: 1.42-2.78). CONCLUSION: Psychological problems are greater after RSA. Therefore, it is suggested that the treatment of RSA emphasizes psychological counseling and psychological management.

Interleukin 10, lipid profile, vitamin D, selenium, metabolic syndrome, and serum antioxidant capacity in elderly people with and without cardiovascular disease: Amirkola health and ageing project cohort-based study.

BACKGROUND: The age-related autoinflammation-mediated atherosclerosis is associated with some immunological, nutritional, and metabolic parameters and redox status. Here, we evaluated the association of circulatory interleukin 10 (IL-10) levels with lipid profile, some nutrients, and total anti-oxidant capacity in elderly people who presented cardiovascular disease (CVD) with or without metabolic syndrome (MetS) and in healthy subjects. METHODS: In this cross-sectional case-control study, 258 sera prepared from elderly people (144 healthy and 114 patient subjects) who participated in a community-based study, the Amirkola Health and Ageing Project (AHAP), were analyzed for IL-10, lipid profile, vitamin D, selenium (Se), antioxidant capacity, and MetS. RESULTS: Compared to patients, the healthy subjects exhibited higher levels of circulatory IL-10 among individuals with detectable serum IL-10 (P = 0.036). However, this difference was not observed when total subjects from both groups were compared, since more than 90% of those people were IL-10-negative. Se, vitamin D, and antioxidant levels were similar in both groups. There was a negative association between IL-10 and body mass index (BMI) (P < 0.050) and an equivocal association with vitamin D levels, whereas the association between IL-10 and other indicated variables was not significant. Significant association was observed between MetS and CVD prevalence (P < 0.001). There was a positive correlation between Se and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (P < 0.010) in healthy subjects and with TC in patients (P < 0.050). CONCLUSION: A major proportion of elderly people were serum IL-10-negative, whereas independently to IL-10, MetS was most common in patients with CVD. Weight loss may have the potential to increase IL-10 levels in the elderly.

Human PBMCs fight or flight response to starvation stress: Increased T-reg, FOXP3, and TGF-ß1 with decreased miR-21 and Constant miR-181c levels.

Regulatory T-lymphocytes play a prominent role in autoimmunity, allergy, and cancer. In some conditions such as inflammation and tumor, immune cells are encountered with metabolic stress. Emerging evidence indicates the contribution of microRNAs in both metabolism and immune regulation. Herewith, we have examined the in vitro effects of serum starvation for 16, 48, 72 and 96 h on the expression of T-reg differentiation markers (CD4, CD25, CD127, and FOXP3) as well as on the Transforming Growth Factor-ß1 (TGF-ß1) and some microRNAs (miR-21,-29a,-31,146a,-155,-181a and -181c) levels in human Peripheral Blood Mononuclear Cells (PBMCs). The percentage of CD4+CD25+CD127low/-FOXP3+ T-regs, as well as FOXP3 expression, was increased in starved lymphocytes (p < 0.01). 96 h-starved PBMCs had the lowest T-eff/T-reg ratio (p < 0.05). All the studied miRNAs except miR-181c were significantly down-regulated in those cells (p < 0.05), in particular, miR-29a and miR-155 were sharply declined in 48h-starved PBMCs (p < 0.01). There was a negative correlation between time of starvation and microRNAs expression, except for miR-181c (r-value = -0. 61 to -0.9 and p-value = 0.037 to 0). The percentage of T-reg was inversely correlated with all miRNAs levels except for miR-31 and miR-181c (r-value = -0.68 to -0.78 and p-value = 0.015 to 0.003). FOXP3 expression exhibited a same degree of negative correlation with miR-31 and miR-155 expression levels (r = -0.57 and p = 0.05, for both). Increasing starvation duration led to a rise inTGF-ß1 protein levels (p<0.01), especially its active form (P<0.001). This study introduced the serum starvation as a tool for immunoregulation which acts probably through increasing TGF-ß1 production and inducing some alterations in microRNAs expression.

Comparison of Salivary and Serum Soluble CD44 Levels between Patients with Oral SCC and Healthy Controls

Background: The most common type of oral cancer is oral squamous cell carcinoma. If it is diagnosed in the early stages; the success of the treatment can be increased. It seems that ELISA-based techniques as a screening tool for society are the most cost-effective methods for early diagnosis. CD44 is a key marker for the detection of SCC stem cells. The aim of this study was to compare the level of soluble CD44 in saliva and serum between patients with oral SCC and healthy controls. Materials and Methods: Saliva and serum were collected from 20 patients with primary OSCC and 20 healthy persons as control group. The samples were evaluated by an ELISA test kit. Data were analyzed by SPSS software version 22, chi-square, ANOVA, T-test and Spearman correlation test. Results: The mean of soluble CD44 level in serum and saliva of the patient and control groups are 531.51±228.95 and 453.3±113.74 (for serum) and 48.53±59.02 and 17.76±39.14 (for saliva) respectively. There was no statistically significant difference in serum and saliva solCD44 level between the patient and control groups (P value = 0.182 and P value = 0.061 respectively). Also, there was no significant correlation between the solCD44 level in each patient and control group in serum (P value = 0.61) and in saliva (P value = 0.445). Conclusions: Determination of solCD44 level in saliva and serum can be a useful method for diagnosis the person's involvement with cancer cells and the cancer in the early stages. But according to the controversial outcomes of past studies, larger and more accurate studies are needed in groups with more cases of oral cancer.

Evaluation of peripheral blood NK cell subsets and cytokines in unexplained recurrent miscarriage.

BACKGROUND: Recurrent miscarriage is considered as one of the main problems in women's reproductive health. The aim of the present study was to evaluate the natural killer cells (NK cells) and cytokines in unexplained recurrent miscarriage and fertile women. METHODS: In this case-control study, 40 women with unexplained recurrent miscarriage were assigned to the case group and 40 fertile women were assigned to the control group. NK cell subsets (CD56+ CD16+/CD56+ CD16-) and cytokines (IL-2/IL-12) levels in the peripheral blood (PB) were used for assessing immunologic problems. The percentage of peripheral blood NK cells (CD56dim/bright) was identified by flow cytometry. RESULTS: The obtained results showed a significant difference in CD56+ CD16+ and CD56+ CD16- between the two groups. Also, there was no significant difference in the IL-2 and IL-12 between the two groups. A cut-off value of ≥5.25% (p < 0.001) and ≥3.4% (p < 0.015) for the increased percentage of CD56+ CD16+ and CD56+ CD16-cells in the PB become predictive of recurrent miscarriage. CONCLUSION: Increased NK cells in the PB of women with recurrent miscarriage strongly establish prospective researches to recognize the predictive value of these parameters in the evaluation of patients with recurrent miscarriage.

TLR2 Arg677Trp but not TLR2 -196 to -174 ins/del and Arg753Gln polymorphism alter the risk of peptic ulcer in north of Iran.

BACKGROUND: Most polymorphisms that occur in TLR-2 are associated with gastrointestinal disorders such as peptic ulcer disease (PUD). Hence, in current study, association between TLR2-196 to -174 ins/del, Arg753Gln and Arg677Trp polymorphisms and risk of PUD development in north of Iran was evaluated. METHODS: This case-control study included 50 patients with PUD as cases and 50 people without peptic ulcer as control group. Blood and endoscopic biopsies were collected. Helicobacter pylori infection was screened by rapid urease test, specific IgG measurement and specific PCR for glmM gene. Then, TLR2-196 to -174 ins/del polymorphism was assessed by using allele-specific PCR. The Arg753Gln and Arg677Trp polymorphism in TLR2 gene were analyzed by the PCR-restriction fragment length polymorphism (RFLP). RESULTS: There was no significant difference in the allele and genotype frequencies of polymorphisms in the TLR2-196 to -174 ins/ins and Arg753Gln genes between controls and patients, respectively. However, an association with increased risk for PUD was observed for polymorphism TLR-2 Arg677Trp (odds ratio [OR] = 7.9; 95% confidence interval [CI] = 0.94-67.5). Further analysis showed that H. pylori infection was associated with a significant difference in genotype and allele frequencies of TLR2-196 to -174 ins/ins and Arg753Gln polymorphism, respectively. Furthermore, there was no association between variant haplotypes and PUD development in H. pylori infected subjects. However, no association was detected between gender and genotypic frequencies of all polymorphisms in TLR2. CONCLUSION: Our findings showed that TLR2 Arg677Trp polymorphism and H. pylori infection may play crucial roles in peptic ulcer development respectively in north of Iran.

Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran.

Toll-like receptor-4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR-restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non-peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35-13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08-0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2-fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran.

Evaluation of the Prevalence of Temporomandibular Joint Involvement in Rheumatoid Arthritis Using Research Diagnostic Criteria for Temporomandibular Disorders.

OBJECTIVES: Temporomandibular joint (TMJ) disorders, known as TMDs, are significant public health problems and may result in pain and disability. In order to determine the prevalence of clinical/subjective TMD in rheumatoid arthritis (RA), we used the research diagnostic criteria (RDC)/TMD axes. We assessed the anti-cyclic citrullinated protein (anti-CCP)-related TMD in RA for the first time. MATERIALS AND METHODS: Fifty-two RA patients were compared to 47 healthy controls with regard to complete blood count (CBC), serology, acute phase reactants (APR), and TMJ dysfunction. RESULTS: The anti-CCP antibody showed a significant correlation with the development of clinical TMD (P=0.001, 95% confidence interval (CI)=12.4%-35.6%). A prevalence of 50% was calculated through the RDC/TMD for such disorders. In RA patients, statistically significant differences were observed between the groups with and without clinical TMD regarding psychological depression and physical symptoms. CONCLUSIONS: According to the results, a significant correlation was found between the anti-CCP antibody and TMD. Therefore, when this antibody is detected in the blood serum, the treatment must be initiated. The RDC/TMD used in this study assessed the prevalence of TMJ dysfunction in conformity with RA-associated TMJ findings previously obtained through other conventional methods.