Clinical heterogeneity in families with multiple cases of inborn errors of immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.

Study of NLRP3 Single Nucleotide Polymorphisms in Juvenile Systemic Lupus Erythematosus (JSLE).

Juvenile systemic lupus erythematosus (JSLE) is a multifaceted multifactorial disorder with an unclear etiopathogenesis. Environmental factors, genetic factors, and dysregulated and defective immune system responses are known to have a role in JSLE etiopathogenesis. NLRP3 inflammasome, as an important contributor to immune-mediated inflammatory responses, is assumed to be involved in JSLE etiopathogenesis. To determine whether the NLRP3 genetic variants are altered in patients with JSLE. Fifty-three patients diagnosed with JSLE and 56 healthy sex-matched controls were studied. NLRP3 (C/G rs10754558, C/T rs3806265, C/T rs4612666, A/C rs35829419) gene polymorphisms were evaluated using a TaqMan single-nucleotide polymorphism assay. C allele at position rs3806265 was detected in higher frequencies in patients than in the control group (37.74% vs 23.21%, P-value = .028). At the genotype level at the same position, CT has a significantly higher frequency in patients than the healthy subjects (75.47% vs 46.43%, P-value = .003). The NLRP3 rs3806265 CT genotype was detected at a higher frequency in patients with JSLE than in the healthy control group.

Comparison of five DNA extraction methods in three medicinal plants: Peganum harmala L., Tamarix ramosissima Ledeb., and Potentilla reptans L.

Extracting high-yield, high-quality DNA from plant samples is challenging due to the presence of the cell wall, pigments, and some secondary metabolites. The main CTAB method, two of its modified protocols (beta-mercaptoethanol or ammonium acetate were eliminated), the modified Murray and Thompson method, and the Gene All kit were statistically compared based on the quantity and quality of the total DNA (tDNA) extracted from fresh and dried leaves of three medicinal herbs P. harmala, T. ramosissima, and P. reptans. The suitability of the tDNAs for molecular studies was evaluated by polymerase chain reaction (PCR) of the fragments of the internal transcribed spacer (ITS) in nuclear DNA and the trnL-F region in chloroplast DNA. Some significant differences were found between the tDNAs extracted by five extraction methods. With the exception of P. harmala, where the PCR of both the ITS fragments and the trnL-F region worked successfully in all DNA samples, but only the ITS fragments, not the chloroplast trnL-F region, were amplified in the DNA samples of T. ramosissima and P. reptans. The chloroplast trnL-F region was amplified only in DNA samples extracted from fresh and dried leaves of the three studied herbs using the commercial kit. Gene All kit, the main CTAB method, and its modified protocols were the less time-consuming protocols that yielded DNA suitable for downstream PCR vis-a-vis the modified Murray and Thompson method.

MGMT Gene rs1625649 Polymorphism in Iranian Patients with Brain Glioblastoma: A Case Control Study.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

BACKGROUND: Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. METHODS: A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. RESULTS: The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). CONCLUSIONS: Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Diversity of malignancies in patients with different types of inborn errors of immunity.

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Characterization of exopolysaccharide produced by probiotic Enterococcus durans DU1 and evaluation of its anti-biofilm activity.

Exopolysaccharides (EPS) produced by lactic acid bacteria are complicated polymers with industrial applications. LAB were isolated, screened for EPS production, and their probiotic properties determined. The anti-biofilm activity of EPS was investigated. Safety of EPS-producing isolate was investigated and it was molecularly identified through 16S rRNA sequencing. Finally, anti-biofilm and emulsification activity of EPS was studied and it was characterized using FT-IR, TGA, 1H-NMR, DLS and HPLC. Thirteen LAB were isolated from dairy products. They showed probiotic characteristics like acid resistance (0-6.51 CFU ml-1) hydrophobicity (8-54.04%), autoaggregation (0% [t = 2 h]-99.8% [t = 24 h]) and coaggregation with food borne pathogens. Among them, Enterococcus durans DU1 had ability to produce EPS. EPS of Enterococcus durans DU1 showed antibiofilm activity against Y. enterocolitica (24.06-51.36%), S. aureus (12.33-49.6%), and B. cereus (11.66-27.16%). FT-IR showed this EPS had characteristic absorption peaks due to the presence of the pyran ring of sugars. 1H NMR showed that EPS has N-acetyl, methyl, and alkyl groups in its structure. The HPLC analysis showed that EPS is a heteropolysaccharide and consists of sucrose, glucose, and fructose. EPS showed significant thermal stability (20% weight loss) under 300 °C and zeta potential of - 18.1 mV. This EPS can be used in the food industry with no adverse effect on consumers.

Adjuvant Effects of Pseudomonas aeruginosa Flagellin on the Immunological Patterns of the HIV-1 Vaccine Candidate: Vaccine Formulations Versus Different Routes of Immunization.

New strategies to increase the immune response to HIV-1 vaccine using immunological adjuvants such as Toll-like receptor agonists are needed. In this study, HIV-1 p24-Nef and conjugated form of the vaccine candidate to type-A flagellin (FLA) were injected in the BALB/c mice in different routes. Two weeks after the last immunization, lymphocyte proliferation was measured by the BrdU method. The IL-4 and IFN-γ levels, as well as the total IgG antibody and its isotypes titer, were evaluated by the enzyme-linked immunosorbent assay method. The IFN-γ ELISPOT was also performed. Our data showed that the HIV-1 p24-Nef alone and conjugated to type-A flagellin (FLA) significantly increased lymphocyte proliferation responses as well as higher levels of cytokines and IFN-γ producing lymphocytes and the level of humoral immune responses compared with the control groups. The cell-mediated immune responses through the subcutaneous route and humoral immune responses through the intramuscular route were significantly higher in the conjugated form than in the mere vaccine candidate. In conclusion, when the FLA as an adjuvant is constructed in the HIV-1 vaccine candidate, it could effectively improve both humoral and cellular immune responses. Furthermore, modification in the vaccine formulation could change the optimal route of vaccine inoculation.

AMELX and ENAM Polymorphisms and Dental Caries.

Introduction: The variety of the genetic factors playing role in development of dental caries calls for further research in this regard. The aim of the present study was to investigate the differences between caries-free adults and adults with dental caries in terms of polymorphism of caries-related genes (AMELX and ENAM). Methods: The present case-control study was performed on 81 adults aged 18-24 years, 41 caries free, and 40 with a DMFT ≥ 4. A questionnaire containing background and demographic information (such as age, gender, time and type of latest dental check-ups, parent's education, oral self-care, and the place of residence in the first 12 years of life) was completed by participants at the time of examination. The blood sample was taken from each participant in the EDTA tube, and PCR was performed. Gene diversity of AMELX and ENAM genes was compared between the two groups. Results: Regarding AMELX gene, in the caries-free group 33 (80.5%) and in the group with DMFT ≥ 4, 33 (82.5%) students had TT genotype, but this difference was insignificant. For ENAM gene, in the caries-free group 34 (82.9%) and in the group with DMFT ≥ 4, 39 (97.5%) students had TT genotype, but this difference was insignificant (P value = 0.048, CI 95%:0.02-1.27, and OR = 0.145). Conclusion: There was no relationship between TT and TC genotypes of single nucleotide polymorphism of AMELX and ENAM gene and susceptibility to dental caries, but with increasing sample size, there may be a relationship between SNP of ENAM gene and being caries free.

The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study.

Menopause is the last menstrual period associated with a decline in ovarian steroid secretion and follicular loss. Hormone profile changes during menopause include a decrease in the production of estrogen, dehydroepiandrosterone (DHEA), and prolactin (PRL), and an increase in thyroid-stimulating hormone (TSH) and cortisol. Herbal medicines are considered as alternatives to hormone therapy. The studies on postmenopausal women have shown that Elaeagnus angustifolia L. (called "Senjed" in Persian) has some efficacy in improving sex hormone and lipid profiles, joint pain, and cardiovascular function, as the decrease in luteinizing hormone, low-density lipoprotein, and heart rate was significant. The aim of the present study was to evaluate the effects of E. angustifolia on TSH, DHEA-S, PRL, and cortisol levels and their ratios in postmenopausal women. It is assumed that the eventual effects of hormones on the brain and other tissues are determined by the balance between interdependent hormones. In the present randomized double-blinded placebo-controlled trial (https://en.irct.ir/search/result?query=IRCT20170227032795N4), fifty-eight postmenopausal women were randomly assigned to one of two medicinal herb (15 g of the whole E. angustifolia fruit powder) and placebo (7.5 g isomalt + 7.5 g cornstarch) groups. After 10 weeks of the treatment, the serum levels of TSH, DHEA-S, PRL, cortisol hormones, and their ratios were measured. The increase in the TSH, and cortisol levels, and cortisol/DHEA-S ratio and the decrease in prolactin and DHEA-S and the PRL/TSH, PRL/cortisol, and DHEA-S/TSH ratios after E. angustifolia consumption were significant only based on within-group but not on the between-group analysis. Based on between-group analyses, the changes in the hormone profile were not significant in the placebo group. According to Iranian tradition and folklore, E. angustifolia fruit is a symbol of female fertility. Therefore, its consumption is highly recommended to maintain health in the elderly, especially women. However, the observed outcomes about the effect of E. angustifolia on menopause were not completely in line with the Iranian folklore. E. angustifolia consumption did not significantly affect the hormone profile and ratios at the end of the ten-week trial, possibly due to the small sample size, short time, and the fact that our participants were postmenopausal women.

Interleukin 9 serum level and single nucleotide polymorphism in patients with asthma.

BACKGROUND: Asthma is a chronic inflammatory disease of airways which accounts for a huge economic, morbidity and mortality burden. There are different cytokines that contribute to asthma pathophysiology. Learning about these cytokines leads to attaining novel anti-inflammatory treatments for asthma control. OBJECTIVES: The objective of this study is to investigate the association between interleukin-9 serum level and gene polymorphism with asthma susceptibility. METHODS: This was a case-control study of 70 asthmatic patients and 77 healthy control adults aged 18-60. Asthma diagnosis and severity were based on physician diagnosis, pulmonary function test (PFT) and 2016 guild line of Global Initiative for Asthma (GINA). Interleukin 9(IL -9) serum level was measured using sandwich enzyme linked immunosorbent assay.  IL9 promoter single nucleotide polymorphism (SNP) (rs2069882) was also assessed using Real-Time PCR System. RESULTS: There was no significant association between IL-9 SNP polymorphism and asthma. IL-9 serum level was significantly associated with asthma susceptibility (p value= 0.016) and absolute eosinophil count (AEC) (P value=0.033) however its corelation with atopic asthma type, asthma sivierity and Immunoglubin E serum level were not statistically significant. CONCLUSION: Although there was no association between IL-9 SNP and asthma, but IL-9 serum level was significantly correlated with asthma susceptibility and AEC.

Lymphocytes subsets in correlation with clinical profile in CVID patients without monogenic defects.

Objectives: Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy, and lymphoproliferation. We evaluated the correlation of lymphocyte subpopulations with such manifestations.Methods: Twenty-six genetically unsolved CVID patients were subdivided into four phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE), and lymphoproliferative disorders (LP) and examined for lymphocyte subsets by flow cytometry and TCD4+ proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test.Results: We detected reduced memory B and increased total, effector memory (EM), cytotoxic, and activated TCD8+ in IO, AI and CE, decreased plasmablasts, total and naive TCD4+, Regulatory TCD4+ (Treg) and naive TCD8+ in IO and CE, elevated CD21low B and terminally differentiated effector memory (TEMRA) TCD8+ in IO and AI, increased helper T (Th2) and Th17 in IO, decreased Th1 in AI and defective total and naive B and central memory (CM) TCD4+ in CE. IO showed reduced TCD4+ proliferation response.Conclusions: In genetically unsolved CVID patients, increased Th2 and Th17 and reduced Treg is associated with IO, increased CD21low B and TEMRA TCD8+ and reduced Th1 is contributed to AI and reduced total and naive B, CM TCD4+ and naive TCD8+ and expanded total TCD8+ is correlated with CE.

Contamination of obsterics and gynecology hospital air by bacterial and fungal aerosols associated with nosocomial infections.

Bacterial and fungal bioaerosols are a global concern due to nosocomial infections, especially in developing countries. Our study aimed to detect fungal and bacterial bioaerosols in different wards of an obstetrics and gynecology hospital air samples. 240 bioaerosol samples were collected by performing impaction method from different wards of a hospital in the central part of Iran, during two seasons. Fungi genera and bacteria species are recognized by cultivation. Concentrations of bacteria and fungi were ranged from 44 to 75 CFU/m3 and 8 to 22 CFU/m3, respectively. Labor Delivery and Recovery (LDR) and Emergency room had first and second most contaminated air among all the hospital wards. No significant difference between microbial load of wards which used natural ventilation and heating, ventilating, and air conditioning (HVAC) system was observed. The microbial load was not affected significantly by temperature, working shift, and Inpatient Bed Occupancy Rate (IBOR). Fungal load related significantly with relative humidity. Staphylococcus aureus (detected in 48.3% of samples) and Penicillium (27%) were the most predominant isolated bacteria and fungi, respectively. The results revealed that the level of bacteria and fungi responsible for nosocomial infections in the air of this hospital is very low. Although levels of microbial contamination are relatively low, it is important to investigate the effect of bioaerosols on nosocomial infections, especially in neonates.

Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients.

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the ataxia telangiectasia mutated (ATM) gene which encodes a serine/threonine protein kinase. The aims of this study were to investigate class switch recombination (CSR) and to review the clinical and immunologic phenotypes of 3 groups of A-T patients, including A-T patients with CSR defects (CSR-D), A-T patients with selective immunoglobulin A deficiency (IgA-D) and A-T patients with normal Ig level. Methods: In this study, 41 patients with confirmed diagnosis of A-T (16 A-T patients with HIgM, 15 A-T patients with IgA-D, and 10 A-T patients with normal Ig levels) from Iranian immunodeficiency registry center were enrolled. B-cell proliferation, in vitro CSR toward IgE and IgA were compared between three groups as well as G2 radiosensitivity assay. Results: Earliest presentation of telangiectasia was a significant hallmark in A-T patients with CSR-D (p = .036). In this investigation, we found that the frequency of respiratory infection (p = .002), pneumonia (p = .02), otitis media (p = .008), chronic fever (p < .001), autoimmunity (p = .02) and hepatosplenomegaly (p = .03) in A-T patients with HIgM phenotype were significantly higher than the other groups. As expected IgE production stimulation and IgA CSR were perturbed in HIgM patients that were aligned with the higher readiosenstivity scores in this group. Conclusion: A-T patients with HIgM compared to other A-T patients presenting more infections and noninfectious complications, therefore, early detection and careful management of these patients is necessary.

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency.

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.

Design and characterization of new antimicrobial peptides derived from aurein 1.2 with enhanced antibacterial activity.

Antimicrobial peptides (AMPs) are promising alternative agents for treating multidrug-resistant bacterial infections. Aurein 1.2 is a natural 13-amino acid AMP with antibacterial activity against Gram-positive bacteria. In this study, we designed three novel AMPs: aurein M1 (A10W), aurein M2 (D4K, E11K), and aurein M3 (A10W, D4K, E11K) to analyze the effect of Trp substitution and enhancement of positive charge on the activity of aurein 1.2. The AMP probability, physicochemical properties, secondary and tertiary structures, and amphipathic structure were predicted by various bioinformatics tools. After the synthesis of the peptides, their antibacterial activity, hemolysis, cytotoxicity, and structural analysis were assayed. Compared to the selectivity of aurein 1.2, the selectivity of aurein M2 and M3 with a net positive charge of +5 was improved 11.30- and 8.00-fold against Gram-positive and -negative bacteria, respectively. The hemolytic activity of aurein M2 was lower than that of aurein 1.2 and M3, while the higher percentage of human fibroblast cells were alive in the presence of aurein M3. Also, the MICs of aurein M3 toward Staphylococcus aureus and Escherichia coli at the physiologic salt were ≤16, which is recommended as a promising candidate for clinical investigation. Circular dichroism analysis indicated an alpha-helical structure in the peptide analogs that is similar to aurein 1.2 in the presence of 10 mM SDS. Therefore, increasing positive charge can be used successfully as an approach for improving the potency and selectivity of AMPs. Moreover, the beneficial effect of Trp substitution depends on its position and the sequence of peptides.

The effects of Elaeagnus angustifolia L. on lipid and glycaemic profiles and cardiovascular function in menopausal women: A double-blind, randomized, placebo-controlled study.

AIMS: The reduced production of ovarian hormones is considered to be the cause of an increase in the incidence of heart disease in women after menopause. Phytoestrogens are found in various herbal sources and are considered as an alternative to hormone therapy because of structural similarity with oestrogen. Elaeagnus angustifolia L., known as Senjed in Persian, is used in Iranian traditional medicine with various medicinal properties, contains valuable compounds, including two types of phytoestrogens. The aim of the present study was to investigate the efficacy of E. angustifolia fruit on the cardiovascular function, lipid and glycaemic profiles in postmenopausal women. METHODS: In this double-blind placebo-controlled clinical trial, 58 postmenopausal women were randomly assigned into two experimental groups of medicinal herb (15 g/day of the whole E. angustifolia fruit powder) and placebo (15 g/day of isomalt + corn starch). Before the trial and after 10 weeks of the treatment, cardiovascular function (heart rate, blood pressure), serum glycaemic profile (fasting blood glucose; glycated haemoglobin, HbA1C), insulin and lipid profile (total cholesterol, TC; triglyceride, TG; LDL-C and HDL-C) were measured. RESULTS: Heart rate, and serum level of LDL-C and HDL-C significantly decreased after treatment with E. angustifolia. Changes in glycaemic profile were not clinically significant. In addition, some studied biochemical parameters significantly changed in the placebo group. CONCLUSIONS: E. angustifolia was somewhat effective in improving cardiovascular function and lipid profile, as well as the overall health of postmenopausal women. However, the use of isomalt and corn starch in menopausal women needs further investigation.

The effects of Elaeagnus angustifolia L. whole fruit on the sex hormone profile in menopausal women: A double-blind, randomized, placebo-controlled study.

ETHNOPHARMACOLOGICAL RELEVANCE: Menopause is a product of interrupted ovarian activity and decrease in its estradiol production. Herbal medicines as an alternative to hormone therapy are increasingly used by menopausal women. Elaeagnus angustifolia L. (Senjed in Persian) is a well-known herbal remedy with various therapeutic effects according to Iranian traditional medicine which is recommended to relieve the menopausal side effects. The aim of present study was to evaluate the effects of oral intake of whole fruit powder of E. angustifolia on the sex hormones profile in menopausal women. MATERIALS AND METHODS: In present double-blind randomized placebo-controlled trial, 58 eligible women who were referred to Kamali Women Hospital (Karaj, Iran, 2017) were randomly assigned into herbal medicine (15 g E. angustifolia) and placebo (7.5 g cornstarch +7.5 g isomalt) groups. Initially and after 10 weeks of the treatment, serum levels of estradiol, progesterone, testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones were measured. RESULTS: According to between-group analyses, the changes in the studied parameters were not significant between herbal medicine and placebo groups, except for joint pain that improved significantly in herbal medicine group. However, by within-group analysis the levels of FSH and FSH to testosterone showed a significant increase, whereas the level of progesterone decreased significantly after 10 weeks of E. angustifolia consumption. CONCLUSIONS: The improvement of the sex hormone profile was not in a full accordance with Iranian folklore after E. angustifolia consumption in the present menopausal participants. However, considering a strong belief on the beneficial effects of E. angustifolia in Iranian folklore, a long-term studies of larger group participants are needed to evaluate the efficacy.

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

BACKGROUND: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. METHODS: Clinical and immunological data were collected from the 75 patients' medical records diagnosed in Children's Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. RESULTS: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. CONCLUSION: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

BACKGROUND: Alteration in serum expression of Transforming Growth Factor-beta (TGF-ß) and IL-10 have been suggested to play a role in the pathogenesis of Kawasaki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA). METHODS: A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-ß C/T at codon 10 (rs1982073), C/G at codon 25 (rs1800471) and IL-10 A/G at -1082 (rs1800896), C/T at -819 (rs1800871) and A/C at -592 (rs1800872) and their respective genotype and haplotypes. A comprehensive search was performed in MEDLINE and SCOPUS using the keywords of interleukin 10, transforming growth factor beta, and Kawasaki disease. Moreover, previous studies investigating the TGF-ß and IL-10 polymorphisms in KD were evaluated. Review Manager Version 5.1 Software was used to perform meta-analysis. RESULTS: There was no significant association between allelic or genotypic variants in the mentioned polymorphisms in TGF-ß or IL-10 with KD or CAA. The only significant haplotypic variant was TC variant at codon 10, and 25 of TGF-ß polymorphisms were associated with higher risk of KD. Meta-analysis of a total number of 770 patients vs. 1471 healthy controls showed no difference in the frequency of any of the IL-10 genetic variants in KD patients, regardless of the presence of CAA. CONCLUSION: Polymorphisms of TGF-ß or IL-10 are not associated with additional risk for KD in Iranian population. IL-10 polymorphisms at -1082, -819 and -592 positions are not associated with KD, nor do they predict coronary artery aneurysm formation.