Expression of Heat Shock Protein 70 (HSP70) and Astacin Genes of Strongyloides stercoralis as well as HSP70 and HSP17.1 Genes of S. ratti in Adult and Larval Stages of S. stercoralis.

Background: Uncovering the roles and characteristics of pathogenesis-related molecules can help us develop novel management methods in parasitology. In this study, we studied the expression levels of Strongyloides stercoralis heat shock protein70 (HSP70) (Sst-hsp-70) and astacin (Sst-ast) as pathogenesis-related genes as well as the expression of S. ratti HSP70 and HSP17.1 (Sra-hsp-70, Sra-hsp-17.1) in the larvae and adult stages of S. stercoralis. Methods: A hyperinfection isolate of S. stercoralis from Gilan Province, northern Iran was cultivated on nutrient agar. After a couple of days, parasites in different stages of life were collected, and total RNA was extracted. The expression levels of astacin and HSP genes were compared by real-time PCR. Results: Statistically higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in L3 larvae than in adults were observed. However, the expression level of Sra-hsp-17.1 was non-significantly lower in the larval stage than in adult worms. Conclusion: Higher expression levels of Sst-ast, Sst-hsp-70, and Sra-hsp-70 genes in the larval stages of S. stercoralis suggest the potential role of these enzymes in parasite cutaneous invasion and pathogenesis. However, higher expression of Srahsp-17.1 in adult forms is probably involved in resistance and survival mechanisms. The similarity in gene expression between S. stercoralis and S. ratti can provide helpful hints to better understand strongyloidiasis from various perspectives, including pathogenesis, proper diagnosis, and targeted treatment.

Different Gene Expression Patterns of IL-1 Family Members in Parkinson's Disease: Results from Bayesian Regression Model.

Parkinson's disease, the second most prevalent neurodegenerative disorder lacking a recognized etiology, is influenced by oxidative stress and alterations in inflammatory cytokine levels. This study aimed to investigate the expression levels of Interleukin(IL)1 receptor accessory protein (IL-1RAcP), IL1ß, IL1α, IL33, and IL36 genes in blood cells and serum IL-1ß levels in Parkinson's disease patients compared to healthy controls (HCs).I n this case-control study, 44 Parkinson's disease patients and 44 age- and sex-matched HCs were included. Gene expression levels were assessed using Quantitative Real-time PCR, and serum IL-1ß levels were measured via enzyme-linked immunosorbent assay. Advanced statistical analyses using the Bayesian regression model in R software were employed. Parkinson's disease patients exhibited elevated expression levels of IL-1RAcP and IL1ß genes  but decreased levels of IL1α, IL33, and IL36 compared to HCs. Age-based differences were not significant. Regarding gender, IL33 transcript levels were significantly higher in males, and serum IL-1ß levels were increased in patients. Subgroup analysis by gender indicated alterations in IL1ß and IL-1RAcP expression in both genders, while IL1α, IL33, and IL36 showed reduced expression only in males. Remarkably, only female patients displayed significantly higher serum IL-1ß levels than female HCs. These findings suggest that dysregulation of immune-related factors plays a crucial role in Parkinson's disease.

Immune endotyping and gene expression profile of patients with chronic rhinosinusitis with nasal polyps in the aspirin-exacerbated respiratory disease (AERD) and the non-AERD subgroups.

BACKGROUND: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP. MATERIAL AND METHOD: In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1ß, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov-Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant. RESULTS: The mean ± SD age of the studied groups was 37 ± 8.7 years old (21-50) for the AERD, and 40.4 ± 7.7 years old (31-52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups. CONCLUSION: Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies.

IL-1, plays a role in some pathological inflammatory conditions. This pro-inflammatory cytokine also has a crucial role in tumorigenesis and immune responses in the tumor microenvironment (TME). IL-1 receptor accessory protein (IL-1RAP), combined with IL-1 receptor-1, provides a functional complex for binding and signaling. In addition to the direct role of IL-1, some studies demonstrated that IL1-RAP has essential roles in the progression, angiogenesis, and metastasis of solid tumors such as gastrointestinal tumors, lung carcinoma, glioma, breast and cervical cancers. This molecule also interacts with FLT-3 and c-Kit tyrosine kinases and is involved in the pathogenesis of hematological malignancies such as acute myeloid lymphoma. Additionally, IL-1RAP interacts with solute carrier family 3 member 2 (SLC3A2) and thereby increasing the resistance to anoikis and metastasis in Ewing sarcoma. This review summarizes the role of IL-1RAP in different types of cancers and discusses its targeting as a novel therapeutic approach for malignancies.

Antitumor activities of a novel fluorinated small molecule (A1) in CT26 colorectal cancer cells: molecular docking and in vitro studies.

Chemotherapeutic treatment of colorectal cancer (CRC) has not been satisfactory until now; therefore, the discovery of more efficient medications is of great significance. Based on available knowledge, the CXCL12/CXCR4 axis plays a significant role in tumorigenesis, and inhibition of CXCR4 chemokine receptor with AMD3100 is one of the most known therapeutic modalities in cancer therapy. Herein, N, N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) (A1) was synthesized as a potent CXCR4 inhibitor. A1 inhibitory activity was first evaluated employing Molecular Docking simulations in comparison with the most potent CXCR4 inhibitors. Then, the antiproliferative and cytotoxic effect of A1 on CT26 mouse CRC cells was investigated by MTT assay technique and compared with those of the control molecule, AMD3100. The impact of the target compounds IC50 on apoptosis, cell cycle arrest, and CXCR4 expression was determined by flow cytometry technique. Our finding demonstrated that A1 induces a cytotoxic effect on CT26 cells at 60 µg/mL concentration within 72 h and provokes cell apoptosis and G2/M cell cycle arrest in comparison with the untreated cells, while AMD3100 did not show a cytotoxic effect up to 800 µg/mL dose. The obtained results show that A1 (at a concentration of 40 µg/mL) significantly reduced the proliferation of CT26 cells treated with 100 ng/mL of CXCL12 in 72 h. Moreover, treatment with 60 µg/mL of A1 and 100 ng/mL of CXCL12 for 72 h significantly decreased the number of cells expressing the CXCR4 receptor compared to the control group treated with CXCL12. Eventually, the obtained results indicate that A1, as a dual-function fluorinated small molecule, may benefit CRC treatment through inhibition of CXCR4 and exert a cytotoxic effect on tumor cells.Communicated by Ramaswamy H. Sarma.

Investigation of the Relationship between Aspirin-Sensitivity and Poor Response to Medical Management in NSAIDs-exacerbated Respiratory Disease Patients with Sinonasal Polyposis.

Background: NSAID-exacerbated respiratory disease (N-ERD) is a highly heterogeneous disorder with various clinical symptoms. The aspirin challenge test is a gold standard method for its diagnosis, and there are still no reliable in vitro diagnostic biomarkers yet. Oral challenge tests are time-consuming and may be associated with a risk of severe systemic reactions. This study aimed to evaluate whether patients with poor responses to medical management are more susceptible to being aspirin-sensitive. Methods: In this cohort study, after CT scanning of all patients and subject selection, conventional medical treatment was started as follows and continued for three consecutive months: at first, saline nose wash twice per day, intranasal beclomethasone spray one puff in each nostril twice per day, montelukast 10 mg tablet once daily, a ten-day course of oral prednisolone starting with the dose of 25 mg per day and taper and discontinued thereafter. Sinonasal outcome test 22 (SNOT22) was used for the evaluation of symptom severity. Statistical analyses were performed with SPSS version 23, and data were analyzed using an independent samples T-test, paired T-test, and Receiver operating curve analysis. Results: 25 males and 53 females were enrolled in this study, with an average age of 41.56 ± 11.74 years old (18-36). Aspirin challenge test results were positive in 29 (37.2%) patients. The average SNOT22 scores before the treatment were 52.97 ± 17.73 and 47.04 ± 18.30 in aspirin-sensitive and aspirin-tolerant patients, respectively, and decreased to 27.41 ± 16.61 and 24.88 ± 16.72 in aspirin-sensitive and aspirin-tolerant patients after the treatment, respectively. There was no significant difference in SNOT22 scores between the groups. Conclusion: The severity of symptoms before treatment and clinical improvement after treatment are not good predictors of N-ERD.

HOMA-IR mean values in healthy individuals: a population-based study in iranian subjects.

Purpose: Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) is an important indicator of insulin resistance. In this population-based investigation, we sought to report the mean value of HOMA-IR in different subgroups of a large population-based database of Iranian healthy subjects. Methods: This study recruited adult healthy individuals between the ages of 18 to 70 years old to Massoud Medical Laboratory, Tehran, Iran. Fasting insulin was measured by using the Electro Chemiluminescence method using Roche Cobas 6000 e601/602 instrument. Results: The mean ± SD value of the HOMA-IR index in the studied population was 2.11 ± 0.99 (2.5-97.5% percentiles: 0.66-4.50). In addition, the mean ± SD of HOMA-IR index in male and female groups were 2.35 1.0 (2.5-97.5 percentile: 0.57-4.37) and 2.05 ± 1.0 (2.5-97.5 percentiles: 0.53-4.35), respectively. Interestingly, it was observed a significant increment for the HOMA-IR index in the male group compared with the female group in all age subgroups (P < 0.01). Conclusions: Our findings showed the mean value of 2.11 ± 0.99 HOMA-IR in the Iranian healthy population. Considering the large sample size in our study, more clinical investigations in terms of ethnicity should be done to provide a precise standardized HOMA-IR index in the Iranian population. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01099-9.

High resolution melting curve analysis for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

Since the emergence of the original Wuhan SARS-CoV-2 strain, several new variants of the virus have emerged. Alpha, Beta, Gamma, Delta and the most recent Omicron variants have been introduced during this pandemic. Several methods including, but not restricted to, allele-specific PCR, ligation with rolling circle amplification and real-time PCR with allele-specific probes are able to detect mutations as low as a single nucleotide polymorphism. High-resolution melting curve analysis is ano-ther technique to assess any mutations in a nucleic acid chain. Confirmed samples with SARS-CoV-2 infection were subjected to variant identification using a de novo-designed HRM assay. In order to select for mutations with the highest effect on Tm of the amplicon, deletion mutations of NSP6 (Del 3675-3677), and S1 (Del 144) were chosen for HRM analysis. HRM analysis for the amplicon of the primer set-1 (NSP6) resulted in Tm differences of -0.39°C, +0.4°C, and -0.6°C between Alpha, Delta, and Omicron variants, respectively, in comparison to the original Wuhan strain. Moreover, HRM analysis of the amplification performed by primer set-2 (S1) led to Tm differences of +0.32°C, -0.26°C, and +0.24°C between Alpha, Delta, and Omicron variants, respectively, in comparison to original Wuhan strain. The test was able to specify each sample to its variant group with more than 90 percent of confidence. The results obtained in this study demonstrate that using a single closed-tube strategy with a HRM-equipped machine, screening new variants of the virus is possible in a fast and reliable way. Keywords: high resolution melting; SARS coronavirus 2; mutation; variant; genotyping.

Expression profiling of inflammation-related genes including IFI-16, NOTCH2, CXCL8, THBS1 in COVID-19 patients.

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant higher CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.

Comparison of circulating miR-148a and miR-126 with autoantibodies as biomarkers of lupus nephritis in patients with SLE.

Lupus nephritis (LN) is the main manifestation of systemic Lupus Erythematosus (SLE). MicroRNAs (miRNAs) and autoantibodies could be suitable candidate biomarkers of LN. This study evaluates the expression of circulating miR-148a and miR-126 along with anti-dsDNA, anti-C1q, and anti-C3b autoantibodies in SLE patients with LN (SLE + LN). 30 women with SLE, 30 women with SLE + LN, and 25 women as healthy controls (HCs) were enrolled in this study. The plasma expression of selected miRNAs was evaluated by real-time PCR. The serum level of anti-dsDNA, C1q, and C3b antibodies was measured by the ELISA. The expression of miR-148a was significantly increased in SLE and SLE+LN groups compared with the control group. No significant difference was found in the expression of miR-126 among the groups. The frequency of autoantibodies was significantly higher in the SLE + LN group than SLE. The Higher levels of circulating miR-148a in the SLE samples compared with the HCs suggest that this miRNA could be a reliable biomarker for SLE patients (with or without LN). Also, autoantibodies against dsDNA, C1q, and, C3 could be used for the prediction of SLE nephritis, independently. However, further studies are needed to confirm these findings.

Expression Pattern of Inflammatory and Anti-Inflammatory Cytokines and Key Differential Transcription Factors in Peripheral Blood Mononuclear Cells of Iranian Coronavirus Disease 2019 Patients with Different Disease Severity.

The purpose of this research was to investigate the gene expression levels of inflammatory cytokines interferon (IFN)γ, tumor necrosis factor (TNF)α, interleukin (IL)1ß, IL2, IL6, IL8, and IL17, and anti-inflammatory cytokines IL4, IL10, IFNα, and IFNß, as well as relevant key transcription factors (TFs), including GATA3, PU1, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), BCL6 (B cell lymphoma 6 protein), FOXP3 (forkhead box P3), RORγt, and T-bet (T-box expressed in T cell) in Iranian patients with moderate and severe coronavirus disease 2019 (COVID-19). Fifty-six patients with COVID-19, and 25 healthy controls (HCs) age and sex matched were investigated. Based on the interim guidance of COVID-19 from the World Health Organization, the patients were classified into 33 moderate and 23 severe patients with COVID-19. The gene expression levels of cytokines and relevant TFs were quantified in peripheral blood mononuclear cells by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression levels of TFs RoRγ (RAR-related orphan nuclear receptor γ), NF-κB, and T-bet were significantly higher in patients with COVID-19 compared with HCs. Furthermore, the gene expression levels of cytokines, including IL2, IFNγ, IL6, TNFα, IL1ß, IL8, and IL17, were significantly higher in patients with COVID-19 than HCs. However, there was a significant increase for IL6, TNFα, and IL17 in severe compared with moderate patients with COVID-19. Finally, The Spearman correlation analysis revealed a significantly positive correlation for IL6 and TNFα, IL6 and IL2, IL6, IFNγ, and IL2 and IFNγ. These data suggest that expression of IL6, TNFα, and IL17 as well as the synergic effect of elevated values of IL2 and IFNγ should be considered in the treatment and management of patients with severe COVID-19.

The Effectiveness of Oral Immunotherapy in Patients with Sesame Anaphylaxis using Omalizumab.

OBJECTIVE: Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. METHODS: In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after confirmation by oral food challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. RESULTS: All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. CONCLUSION: This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab appears to have reduced the severity of reactions.

Human papilloma virus (HPV) and prostate cancer (PCa): The potential role of HPV gene expression and selected cellular MiRNAs in PCa development.

BACKGROUND: Prostate cancer (PCa) is one of the most common and health-threatening cancers in men worldwide. The human papillomavirus (HPV) is considered one of the organisms with the potential to be involved in the progression of this cancer. In the present study, we evaluated the association between the expression levels of HPV genes with the expression of selected cellular miRNAs (miR-19a, miR-21, miR-23b, miR-34a, miR-150-5p, and miR-155) and their targets genes (P53, Rb, c-Myc, TIMP-1, MMP-2, MMP-9, PDCD4, Bcl-2, and Survivin) in PCa tissue samples. METHODS: HPV detection and genotyping were performed on the tissues of 112 PCa patients and 39 healthy individuals. The expression profile of miRNA was evaluated by SYBR Green-based real-time PCR. As well Human Survivin ELISA Kit was utilized to determine the concentrations of Retinoblastoma, P53, survivin, Bcl-2, c-Myc, TIMP-1, MMP-2, MMP-9, and PDCD4 in the prostate tissues. RESULTS: According to our findings, HPV genome was detected in 28.7% (21/73) of PCa tissue specimens and 17.94% (7/39) control samples. There was no significant association between the presence of HPV infection with PCa (OR = 2.01, 95%CI = 0.8-5.68, P = 0.102). We found that mean expression level of miR-19a (3.7 ± 4.3, p-value: 0.0007), and -21 (2.5 ± 2.8, p-value<0.0001) were significantly higher and miR-23b (-2.14 ± 3.08, p-value: 0.003) and -34a (-3.12 ± 3.28, p-value: 0.0001) levels were significantly lower in PCa tissue samples than in control tissue samples. CONCLUSION: Present research indicated that HPV positive PCa has a distinct miRNA profile compared with HPV negative PCa.

The roles of interleukin-1 receptor accessory protein in certain inflammatory conditions.

Interleukin-1 receptor accessory protein (IL-1RAcP) is a member of the immunoglobulin superfamily proteins consisting of soluble and membranous isoforms. IL-1RAcP plays an essential role in the signaling of the IL-1 family cytokines such as IL-1, IL-33 and IL-36, as well as tyrosine kinases FLT3 and C-Kit. IL-1RAcP generally initiates inflammatory signaling pathway through the recruitment of signaling mediators, including MYD88 and IRAK. Chronic inflammation following prolonged signaling of cytokine receptors is a critical process in the pathogenesis of many inflammatory disorders, including autoimmunity, obesity, psoriasis, type 1 diabetes, endometriosis, preeclampsia and Alzheimer's disease. Recently IL-1RAcP aberrant signaling has been considered to play a central role in the pathogenesis of these chronic inflammatory diseases. Targeting IL-1RAcP signaling pathway that was recently considered in clinical trials related to malignancies also indicates its potential as therapeutic target for the inflammatory and autoimmune diseases. This review summarizes the molecular structure, components associated with IL-1RAcP signaling pathways, and their involvement in the pathogenesis of different inflammatory diseases. We will also discuss the effect of IL-1RAcP inhibition for treatment proposes.

The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies.

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.

Reference interval of antithrombin, protein C, and protein S activities in healthy adults in Iran, the effect of age, sex, oral contraceptive intake, and menopause.

BACKGROUND: Antithrombin (AT), protein C (PC), and protein S (PS) are natural anticoagulant proteins that deficiency in each of them is associated with an increased risk of venous thromboembolism.The overlapping of plasma levels of AT, PC, and PS between healthy individuals and heterozygote carriers poses significant challenges in precise diagnosis. This study aimed to evaluate the effect of most influencing variables on plasma levels of these proteins and propose specific reference intervals to improve the interpretation of the laboratory results. METHODS: This study was conducted on 1464 individuals who were referred to Massoud medical laboratory, Tehran, Iran, from 2019 to 2020. AT and PC were measured through chromogenic assay and PS plasma level with the clot-based assay. A multivariable linear regression model was performed to evaluate the effect of sex, age, oral contraceptive (OCP) intake, and menopause state. Normal deviate z value was used for different subgroups to justify the need for a separate reference interval. RESULTS: 1200 verified healthy individuals (434 males and 766 females), aged between 18 and 69 years were included in the study. The mean ± SD age of the participants was 39.78 ± 11.79 years. The age-related effects for AT were found in men. In females, increasing age was associated with a rise in AT, PC, and PS plasma levels. No sex difference was found in AT plasma level. OCP-taking is associated with a decrease in AT and an increase in PC plasma levels. CONCLUSION: This is the largest study ever conducted on healthy individuals in the Iranian population, using specific reference interval results in accurate diagnosis of true AT, PC, and PS deficiency.

Oral Wheat Immunotherapy: Long-Term Follow-Up in Children with Wheat Anaphylaxis.

INTRODUCTION: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. METHODS: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). RESULTS: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). CONCLUSION: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.

Atopy Patch Test in the Diagnosis of Food Allergens in Infants with Allergic Proctocolitis Compared with Elimination/Introduction C.

Allergic proctocolitis is a cell-dependent food allergy that is present in both breast and formula-fed infants. The presence of blood with different amounts in the stool is the main manifestation of the disease. Different results have been published on the accuracy and specificity of the atopic patch test (APT). The purpose of this study was to evaluate the results of the APT and compare them with those obtained in the food elimination/introduction (E/I) challenge, as the gold standard of confirming the allergy. Twenty-eight patients (18 boys, 10 girls, <1 year) with allergic proctocolitis were recruited in this study. The mean age of the disease onset and enrolling the study were 2.23±1.7 and 5.25±2.19 months, respectively. After performing APT with fresh foods, an E/I challenge was done in a patient with positive tests, and results were analyzed. APT was positive in 14/28 (50%) individuals. The most common foods detected by APT in all of the individuals were: milk (10/28), rice (5/28), soy (4/28), and egg white (4/28), while in E/I challenge in the APT-positive individuals were: milk (8/10), rice (3/5), egg white (1/4), and soy (0/4). APT was positive in half of the infants<1 year with allergic proctocolitis and there was no significant correlation between the APT results and the E/I challenge test for all foods. Comparing the results of APT and E/I challenge methods showed a convergence between the milk and rice sensitivity, thus we suppose APT to be a useful tool in identifying these two allergens in cell-mediated food allergies like allergic proctocolitis.

Vitamin E and selenium improve mesenchymal stem cell conditioned media immunomodulatory effects.

BACKGROUND: Mesenchymal stem cells (MSCs) with immunoregulatory properties affect immune systems. Many studies showed that antioxidants such as vitamin E (Vit E) and selenium (Se) could improve stem cells survival. This study aims to investigate the effects of MSC conditioned media (CM) treated with Vit E and Se on immune cells. METHODS: MSCs were isolated and cultured with Vit E and Se. Immature dendritic cells (DCs) and peripheral blood mononuclear cells (PBMCs) were cultured with MSC CM treated with Vit E and Se. The expression of HLA-DR, CD86, CD40, and CD83 on mature DC were evaluated. DC supernatant and PBMCs supernatant was collected for the study of TGF-ß, IL-10, and IL-12. PBMCs evaluated for the expression of T-bet, GATA3, RORγt, and FOXP3. RESULTS: MSC CM increased CD40 on myeloid DC (mDC). CD40 has been decreased in DC treated with MSC (Vit E) and MSC (Se) CM. HLA-DR expression on DCs and IL-12 level were significantly reduced in MSC (Vit E) CM. IL-10 concentration increased in DCs treated with MSC (Vit E) and MSC (Se) CM. Treatment of PBMCs with MSC CM decreased IL-10 level, FOXP3, and RORγt expression. On the other hand, the MSC (Vit E) CM and MSC (Se) CM decreased the IL-10 level and increased IL-12, T-bet, and RORγt. CONCLUSIONS: According to the results, the treatment of MSC with Vit E and Se enhanced the ability of MSCs to inhibit DCs and improved immunomodulatory effects. Concerning the effect of MSC on PBMC, it seems that it increased RORγt expression through monocytes.

The fatty acid-binding protein (FABP) decreases the clinical signs and modulates immune responses in a mouse model of experimental autoimmune encephalomyelitis (EAE).

BACKGROUND: An increasing body of studies has shown that Fasciola hepatica can affect immune responses. This study explored whether the fatty acid-binding protein (FABP) of F. hepatica can modulate the immune system in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: EAE-induced C57BL/6 mice were treated with vehicle, F. hepatica total extract (TE) or FABP. The clinical signs, body weights, and the expression of IFN-γ, T-bet, IL-4, GATA3, IL-17, RORγ, TGF-ß, FOXP3, IL-10, TNF-α genes and proteins were determined in the isolated CD4+ splenocytes. Besides, the percentage of Treg cells and degree of demyelination were evaluated. RESULTS: We found that TE and FABP treatments decreased the clinical scores, lymphocyte infiltration rate, and demyelinated plaques in EAE mice. The expressions of IL-4 and GATA3 were increased, whereas IL-17 and TNF-α were down-regulated. FABP did not affect the expression of IFN-γ, RORγ, IL-10, and TGF-ß genes or proteins but reduced the expression of T-bet. TE administration did not affect the expression of IL-10 and the Tbet genes, and increased the expression levels of IFN-γ and FOXP3 in CD4+ lymphocytes. Both FABP and TE treatment did not affect the Treg cell percentage. CONCLUSION: This study indicates that F. hepatica FABP and TE can suppress the inflammatory responses in EAE-induced mice and shift the immune system toward Th2 responses. However, FABP exerts stronger anti-inflammatory effects and seems to be more effective than TE for EAE treatment.