Nexilin in cardiomyopathy: unveiling its diverse roles with special focus on endocardial fibroelastosis.

Cardiac disorders exhibit considerable heterogeneity, and understanding their genetic foundations is crucial for their diagnosis and treatment. Recent genetic analyses involving a growing number of participants have uncovered novel mutations within both coding and non-coding regions of DNA, contributing to the onset of cardiac conditions. The NEXN gene, encoding the Nexilin protein, an actin filament-binding protein, is integral to normal cardiac function. Mutations in this gene have been linked to cardiomyopathies, cardiovascular disorders, and sudden deaths. Heterozygous or homozygous variants of the NEXN gene are associated with the development of endocardial fibroelastosis (EFE), a rare cardiac condition characterized by excessive collagen and elastin deposition in the left ventricular endocardium predominantly affecting infants and young children. EFE occurs both primary and secondary to other conditions and often leads to unfavorable prognoses and outcomes. This review explores the role of NEXN genetic variants in cardiovascular disorders, particularly EFE, revealing that functional mutations are not clustered in a specific domain of Nexilin based on the cardiac disorder phenotype. Our review underscores the importance of understanding genetic mutations for the diagnosis and treatment of cardiac conditions.

Immunometabolism in atherosclerosis: a new understanding of an old disease.

Atherosclerosis, a chronic inflammatory condition, remains a leading cause of death globally, necessitating innovative approaches to target pro-atherogenic pathways. Recent advancements in the field of immunometabolism have highlighted the crucial interplay between metabolic pathways and immune cell function in atherogenic milieus. Macrophages and T cells undergo dynamic metabolic reprogramming to meet the demands of activation and differentiation, influencing plaque progression. Furthermore, metabolic intermediates intricately regulate immune cell responses and atherosclerosis development. Understanding the metabolic control of immune responses in atherosclerosis, known as athero-immunometabolism, offers new avenues for preventive and therapeutic interventions. This review elucidates the emerging intricate interplay between metabolism and immunity in atherosclerosis, underscoring the significance of metabolic enzymes and metabolites as key regulators of disease pathogenesis and therapeutic targets.

The Role of Soluble ACE2 as a Prognostic Marker in Severe COVID-19: A Brief Meta-Analysis.

BACKGROUND: The recently emerged novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has posed a serious threat to public health, and there is an urgent need to establish tools that can aid the clinician in the evaluation and management of highrisk patients. This meta-analysis aimed to investigate the potential of sACE2 (soluble angiotensinconverting enzyme 2) as a prognostic biomarker in COVID-19. METHODS: A comprehensive search of PubMed/MEDLINE, Cochrane, and Google Scholar, was performed until May 26, 2021. Data extraction and quality assessment of the study were independently conducted by the authors. Finally, 6 studies were included in this meta-analysis. RESULTS: ACE-2 serum or plasma levels were compared between COVID-19 patients and healthy controls. ACE-2 level was not significantly different between severe COVID-19 patients and healthy controls (SMD = 1.2; 95% CI: -1.3-1.5; P = 0.86), severe and non-severe COVID-19 patients (SMD = 0.3; 95% CI: -0.06-0.7; P = 0.1), and severe COVID-19 patients and healthy controls (SMD = 0.6; 95% CI: -1.1-2.3; P = 0.5). CONCLUSIONS: We cautiously propose that circulating levels of ACE2 cannot be used as a biomarker to assess disease severity in COVID-19 patients.

Krebs von den Lungen-6 (KL-6) as a clinical marker for severe COVID-19: A systematic review and meta-analyses.

BACKGROUND: Krebs von den Lungen-6 (KL-6) is a molecule that is predominantly expressed by damaged alveolar type II cells, and has been proposed as a marker of COVID-19 and the severity of the disease. Here, we performed a meta-analysis to determine whether KL-6 could be used as a prognostic factor for severe COVID-19. METHODS: PubMed, Cochrane and Google Scholar were searched until April 20, 2021, and 7 studies were included. KL-6 was considered as the outcome and pooled in meta-analyses. RESULTS: All included studies compared KL-6 in severe and non-severe patients. Serum KL-6 was higher in severe COVID-19 patients compared to non-severe (n = 6; SMD = 1.25; 95% CI: 0.99-1.5; P < 0.001) and healthy controls (n = 4; SMD = 3.07; 95% CI: 1.36-4.8; P < 0.001). CONCLUSION: This data collection revealed the potential clinical significance of KL-6 as a non-expensive predictive biomarker in severe COVID-19 and for the categorization of COVID-19 clinical severity.

RORC gene polymorphism is associated with acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiopulmonary bypass (CPB), associated with increased mortality in surgical patients. It is well-proven that Th17 and its hallmark cytokine, IL-17, contribute to AKI development. Since the RAR-related orphan receptor C (RORC) gene is a master regulator of the Th17 differentiation, we aimed to evaluate the association between its polymorphisms, CPB-AKI and plasma IL-17 levels among Iranian patients undergoing CPB. METHOD: Totally, 138 patients undergoing CPB in Bandar Abbas, Iran, were enrolled. The allele and genotype frequencies of the selected SNPs were determined using PCR-SSP. IL-17 serum level was determined using an enzyme-linked immunosorbent assay. RESULTS: Rs9017 GG genotype and G allele were associated with increased risk of CPB-AKI (OR = 3, 95% CI = 1.4-6.6 and OR = 2.3, 95% CI = 1.3-3.9, respectively) while A allele was protective against the disease (OR = 0.4, 95% CI = 0.3-0.7, p = .02). There was not a statistically significant interaction between the three genotypes of rs9017 and AKI disease with IL-17 serum level before (p = .9) and after (p = .6) the operation. The IL-17 serum level before surgery was significantly higher in patients carrying GG genotype compared to GA genotype (p = .017). CONCLUSION: Our results showed that the rs9017 GG genotype was associated with an increased level of IL-17 and risk of CBP-AKI in the Iranian population. Our current results suggest that the rs9017 GG genotype could be a probable predictor of AKI after cardiac surgery.

Lack of association between serum IL-25 levels and acute coronary syndrome: a preliminary study.

Purpose    Here, for the first time, the possible association between IL-25 and the risk of acute coronary syndrome (ACS) in Iranian patients was investigated.Material and methods    In this study, serum IL-25 concentrations were measured with an enzyme-linked immunosorbent assay in 88 ACS patients, 40 stable angina pectoris (SAP) patients, and 50 healthy control subjects.Results    No significant differences in IL-25 concentrations were observed between SAP (340±168 ng / l), ACS (330±151 ng / l), and control (302±135 ng / l) groups (p=0.5), nor was there a difference among patients with 1, 2, or 3 vessel disease in the SAP and ACS groups. Linear regression analyses revealed that IL-25 was not correlated with coronary artery disease risk factors. Biochemical and demographic variables did not differ significantly among IL-25 quartiles.Conclusion    Despite previous murine and human studies showing a protective role of IL-25 in atherosclerosis, our results revealed that IL-25 does not have potential implications for atherosclerosis development and management in humans.

Toward an understanding of regulatory T cells in COVID-19: A systematic review.

A more detailed understanding of Treg cells in COVID-19 infection will broaden our knowledge of the COVID-19 immunopathology and give us more insight into the curative immune-based strategies. We systematically searched electronic databases (PubMed, Google Scholar, EMBASE) and identified 18 eligible studies. Despite the inconsistencies between the results, we observed a trend toward decreasing Treg levels in severe COVID-19 patients. This finding underlines the hypothesis that Tregs play a role in the pathogenesis of COVID-19. Further studies on Tregs' functional aspects are necessary to illustrate Tregs' potential role in COVID-19 disease.

Negative Correlation between Neuregulin-4 and IL-9 Serum Levels in Patients with Coronary Artery Disease.

BACKGROUND: Neuregulin 4 (Nrg4) is a novel adipocytokine that has been proposed to play a role in modulating energy metabolism and pathogeneses of atherosclerosis. However, no published research is available about the mechanisms underlying the anti-atherosclerotic effect of Nrg4. Regarding the close link between adipocytokines and the immune system, we wonder whether there is a relation between Nrg4 and athero-protective cytokines. The aim of this study was to investigate the relationship between serum Nrg4 levels and type 2 cytokines in Iranian patients with coronary artery disease (CAD). METHODS: In this case-control study, 125 CAD patients were compared to 55 healthy controls. The serum concentrations of Nrg4, IL-5, IL-9, and IL-13 were measured using ELISA. The associations of circulating Nrg4 and IL-5, IL-9, IL-13 were assessed using linear regression analyses. RESULTS: Serum concentration of IL-9 was significantly higher in patients compared to the healthy controls (317.9±139 versus 228.3±99.1, P= ˂0.0001). IL-13 and Nrg4 were significantly lower in patients compared to the healthy controls (4.3±3.7 versus 6.1±3.9, P=0.01 and 0.5 versus 1.3, P=0.001 respectively). Multiple linear regression analyses revealed that IL-9 was negatively correlated with Nrg4 (ß= -0.3, P=0.009). CONCLUSION: Our study, for the first time, provides the clinical evidence revealing that circulating Nrg4 concentrations are inversely correlated with IL-9 in Iranian patients with CAD, suggesting that the protective role of Nrg4 on atherosclerosis may be, in part, mediated by the proatherogenic cytokine, IL-9.

Maintenance of quality and bioactive compounds of cold stored pomegranate (Punica granatum L.) fruit by organic acids treatment.

Pomegranate is a subtropical and chilling sensitive fruit. In this study, the effects of malic acid (50 and 100 mM) and oxalic acid (5 and 10 mM) on quality properties of pomegranate during cold storage (2 ℃) were investigated. The lowest weight loss was observed in fruit treated with 50 mM malic acid. Malic acid had positive effects on color parameters (L*, a*, and b*) of pomegranate at low temperature. Organic acid treatments reduced chilling injury, malondialdehyde, and hydrogen peroxide and increased catalase activity. The lowest activity of polyphenol oxidase and peroxidase was observed in 5 mM oxalic acid-treated fruit. On the other hand, fruit treated with 50 mM malic acid showed the maximum ascorbic acid and citric acid content. The most antioxidant activity was found in fruit treated with 5 mM oxalic acid and 50 mM malic acid. Also, all treatments except 10 mM oxalic acid and 100 mM malic acid resulted in higher titratable acidity than control fruit. Overall, 50 mM malic acid and 5 mM oxalic acid were the most effective for preserving the quality of pomegranate fruit at low temperature.

The Relationship Between Serum Concentration of Interleukin-35 and FoxP3 Polymorphism in Patients Undergoing Coronary Artery Bypass Graft Surgery.

OBJECTIVE: To investigate the association between interleukin-35 (IL-35) levels and single nucleotide polymorphisms (rs3761548, rs3761547) of the FoxP3 gene in coronary artery bypass grafting (CABG) patients. METHODS: We conducted a prospective study including 140 patients, who were scheduled for elective isolated on-pump CABG with cardiopulmonary bypass (CPB) from January 2017 to September 2018 in the Jorjani heart center. Blood samples were collected before and 12 hours after the operation. Serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the pattern of genetic variations was assessed using single specific primer-polymerase chain reaction. RESULTS: The serum concentrations of IL-35 after surgery were significantly higher than pre-surgery levels (18.4±8.3 vs. 9.89±3.2, respectively, P=0.002). There was no significant association between genotype frequencies of rs3761548 and rs3761547 and elevated IL-35 levels (P>0.05). There were significant associations between IL-35 levels and preoperative variables, including age (r=-0.34, P=0.047) and body mass index (r=-0.41, P=0.045), and intraoperative variables, including CPB time (r=0.4, P=0.02) and mean arterial pressure (r=-0.38, P=0.046), in carriers of the rs3761548 AA genotype. CONCLUSION: Serum IL-35 concentrations were significantly increased in CPB patients, which may contribute to the post-CPB compensatory anti-inflammatory response syndrome. IL-35 increased levels were not influenced by FoxP3 promoter polymorphisms (rs3761548, rs3761547).

The relationship between serum concentration of interleukin-35 and foxp3 polymorphism in patients undergoing coronary artery bypass graft surgery

Abstract Objective: To investigate the association between interleukin-35 (IL-35) levels and single nucleotide polymorphisms (rs3761548, rs3761547) of the FoxP3 gene in coronary artery bypass grafting (CABG) patients. Methods: We conducted a prospective study including 140 patients, who were scheduled for elective isolated on-pump CABG with cardiopulmonary bypass (CPB) from January 2017 to September 2018 in the Jorjani heart center. Blood samples were collected before and 12 hours after the operation. Serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the pattern of genetic variations was assessed using single specific primer-polymerase chain reaction. Results: The serum concentrations of IL-35 after surgery were significantly higher than pre-surgery levels (18.4±8.3 vs. 9.89±3.2, respectively, P=0.002). There was no significant association between genotype frequencies of rs3761548 and rs3761547 and elevated IL-35 levels (P>0.05). There were significant associations between IL-35 levels and preoperative variables, including age (r=-0.34, P=0.047) and body mass index (r=-0.41, P=0.045), and intraoperative variables, including CPB time (r=0.4, P=0.02) and mean arterial pressure (r=-0.38, P=0.046), in carriers of the rs3761548 AA genotype. Conclusion: Serum IL-35 concentrations were significantly increased in CPB patients, which may contribute to the post-CPB compensatory anti-inflammatory response syndrome. IL-35 increased levels were not influenced by FoxP3 promoter polymorphisms (rs3761548, rs3761547).

Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome.

Acute coronary syndrome (ACS) is closely associated with an increased risk of death. Nrg4, a novel adipocytokine, has negative correlations with indicators of metabolic syndrome. Here, we investigated whether circulating Nrg4 associates with the prevalence of ACS. In this case-control study, a total of 257 subjects (144 patients with ACS and 56 patients diagnosed with stable angina pectoris (SAP)) compared to 57 healthy controls. Serum Nrg4 and hs-CRP concentrations were determined by ELISA. The associations of circulating Nrg4 with other clinical parameters were also analyzed. Serum levels of Nrg4 were lower in patients compared to the control subjects (0.7 ± 0.53 ng/mL versus 1.1 ± 0.9 ng/mL, P = 0.018). There was a significant association between higher Nrg4 level and lower risk of ACS (OR = 0.15; 95%CI = 0.02-0.9; P = 0.046), but not with SAP. This association was independent of potential confounders including traditional cardiovascular risk factors. The distribution of patients with no, 1, 2 and 3 vessel stenosis was significantly different in Nrg4 quartiles. Patients in the lower quartile of Nrg4 were more likely to experience 3 vessel diseases. Serum levels of Nrg4 correlated negatively with HDL-cholesterol in ACS patients. Decreased serum levels of Nrg4 might be an independent risk factor for ACS.

Interleukin -17 Serum Levels and Polymorphisms in Acute Kidney Injury Patients.

BACKGROUND: Cardiopulmonary bypass (CPB) has been demonstrated to provoke a systemic inflammatory response believed to be responsible for some of the serious postoperative complications such as renal dysfunction. Therefore, we tested the hypothesis suggesting that the serum levels of IL- 17A (IL-17), as an inflammatory cytokine, and its gene variants are associated with acute kidney injury after CPB (AKI-CPB). METHODS: A total of 135 Iranian patients undergoing cardiopulmonary bypass were included in this study, of whom 65 (48.1%) developed AKI. Blood specimens were collected preoperatively and at 12 hours postoperatively. The IL-17 gene polymorphisms (rs2275913 and rs3819024) were determined using sequence-specific primers (PCR-SSP) technique.Pre- and postoperative IL-17 levels were measured and analyzed in relation to polymorphisms. RESULTS: IL-17 concentrations in CBP subjects, were increased after cardiopulmonary bypass (P<0.00001)but there were no statistically significant differences in IL-17 serum level between AKI and non-AKI groups. Different genotypes of IL-17 rs2275913 SNP (G→A) were associated with different circulating IL-17 levels before bypass and also after AKI development. There were no associations between gene polymorphisms (rs2275913and rs3819024) and incidence of AKI- CPB. There was an association between thers2275913 SNP and the severity of AKI. CONCLUSION: This study clarified that the rs2275913 SNP to some extent determines plasma IL-17 concentrations in CPB patients. No significant association was found between IL-17 levels or gene polymorphisms (rs2275913and rs3819024) and incidence of AKI-CPB. Our results suggest that there is an association between rs2275913 and the severity of AKI- CPB.

Effectiveness of alginate coating on antioxidant enzymes and biochemical changes during storage of mango fruit.

The climacteric nature of mango makes it ripen quickly and increases its postharvest losses. The objective of the present search was to evaluate the efficacy of 1%-3% sodium alginate edible coating for maintaining the postharvest nutritional quality and increasing the marketability of the mango fruit during storage at 15 ± 1°C and 85 ± 1% relative humidity. Results revealed that the quality characteristics including acidity and ascorbic acid content were not affected by the alginate treatments. In contrast, treatment with 3% alginate significantly reduced weight loss and maintained higher firmness (2-fold), total phenols (1.3-fold), and flavonoids content (1.7-fold), as compared with the control. Higher antioxidant capacity was observed in the 3% alginate treatments than the control. Polyphenolxoidase activity in the coated mango remained below 30 U/g FW, while it was increased continuously in the uncoated samples during the storage. Fruits coated with alginate exhibited a higher antioxidant enzyme activity during storage. Sodium alginate had no significant effects on the external color parameters except the a* value. Generally, it was concluded that the mango storage life and its valuable nutritional characteristics were increased by applying the alginate edible coating. PRACTICAL APPLICATIONS: Recently, the edible coatings by natural sources have been widely demanded by consumers due to its nontoxic and biodegradable characteristics. Mango fruits as a climacteric high-nutritional tropical fruit being climatic have a limited shelf life and the maintenance of its quality is still a major challenge for the consumers. The results of this study showed that using sodium alginate coating at 3% concentration had a significant effect on preventing water loss, color changes and preserving antioxidant properties, phenol and flavonoids compounds of mango fruit during storage. Therefore, alginate coating as a biodegradable compound can be used to maintain the quality during the shelf life of fruits and vegetables.

Cytotoxic impacts of CuO nanoparticles on the marine microalga Nannochloropsis oculata.

The toxic impacts of CuO nanoparticles (NPs) on the marine phytoplankton Nannochloropsis oculata were evaluated by measuring a number of biological parameters. Exposure to different concentrations of CuO-NPs (5-200 mg/L) significantly decreased the growth and content of chlorophyll a of N. oculata. The results showed that CuO-NPs were toxic to this microalga with a half maximal effective concentration (EC50) of 116.981 mg/L. Exposure to CuO-NPs increased the hydrogen peroxide (H2O2) content and induced the membrane damages. Moreover, the concentration of phenolic compounds was increased, while the levels of carotenoids were markedly decreased in comparison to the control sample. The activity of catalase (CAT), ascorbate peroxidase (APX), polyphenol oxidase (PPO) and lactate dehydrogenase (LDH) enzymes significantly was increased in response to CuO-NPs treatments. These results indicated that CuO-NPs stimulated the antioxidant defense system in N. oculata to protect the cells against the oxidative damages. The Fourier-transform infrared spectroscopy (FTIR) analyses showed that the main functional groups (C=O and C-O-C) interacted with CuO-NPs. The images of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the cell membrane damage and the change of cell wall structure which may be contributed to the nanotoxicity. These findings may provide additional insights into the mechanisms of cytotoxicity induced by CuO-NPs.

Preliminary Report on the Association Between STAT3 Polymorphisms and Susceptibility to Acute Kidney Injury After Cardiopulmonary Bypass.

Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a well-recognized complication which is clearly linked to increased morbidity and mortality. Due to important role of inflammation in CPB-AKI pathogenesis, we explored the association between polymorphisms in STAT3, an inflammation-associated transcription factor, and the risk of CPB-AKI. In this study, STAT3 rs1053004 and rs744166 polymorphisms were analyzed in 129 patients undergoing coronary artery bypass grafting in Jorjani heart center, Bandar Abbas, Iran. The genotypes were determined using sequence-specific primers (PCR-SSP). Sixty-three patients met the criteria for AKI after cardiac surgery (AKI group). The remaining 66 patients did not develop AKI (non-AKI group). Rs1053004 GG genotype was significantly associated with a decreased risk (OR 0.4, 95% CI 0.17-0.9, P = 0.03) of CPB-AKI. Subgroup analyses revealed that GG genotype has also a protective effect in older patients (Age ≥ 60) (OR 0.19, 95% CI 0.04-0.8, P = 0.01). However, rs744166 did not show any difference between AKI and non-AKI groups. The result of our study for the first time provides evidence that rs1053004 polymorphism is significantly associated with a decreased risk of CPB-AKI in Iranian population, especially in older subjects.

Vitamin D status in coronary artery disease: association with IL-35 and TGF-ß1 and disease severity.

BACKGROUND: The exact mechanisms underlying the protective effect of vitamin D in the pathogenesis of atherosclerosis and coronary heart disease are obscure. OBJECTIVE: Here, we have addressed the relation between vitamin D status and regulatory T cells (Tregs) inhibitory cytokines in patients suffering from coronary artery disease (CAD). MATERIALS AND METHODS: 81 patients were divided into single (n= 20), double (n=20) and triple (n=20) vessel disease groups and compared to no vessel disease (No VD) group (n=21). Interleukin (IL) -35 and TGF- ß1 were measured using ELISA. Vitamin D was measured using Electrochemiluminescence assay. RESULTS: Vitamin D, TGF-ß1 and IL-35 concentrations in No VD (32.4±15.2, 667.7±427.6, 12.1±11.9 respectively) group were significantly higher than patients with 1 or more vessel disease (18.1±9.8, 360.4±354.1 and 6.8±8.1 respectively, p<0.05). Subgroup analysis revealed that TGF-ß1 and IL-35 (but not vitamin D) were significantly higher in double vessel disease patients (591.9±465.7 and 9.2±8.0 respectively) compared to those with triple vessel disease (173.1±163.3 and 3.6±1.4 respectively, p<0.05). Both TGF-ß1 and IL-35 were positively correlated to the serum level of vitamin D (r= 0.38, p= 0.001 and r=0.26, p= 0.028 respectively). Vitamin D, TGF-ß1 and IL-35 revealed a negative correlation (r= -0.36, r=-0.46 and r-0.024 respectively) with severity of CAD (p< 0.05). Compared to normal serum vitamin D patients (326.6±351.7 pg/mL vs. 754.5±560 pg/mL, p=0.036 respectively) TGF-ß1 (but not IL-35), was significantly lower in vitamin D deficient patients. CONCLUSION: The results suggested that, although decreased TGF-ß1 and IL-35 plasma levels correlate positively with decreased vitamin D levels and negatively with severity of CAD, but only TGF-ß1 has a significant association with vitamin D deficiency in CAD patients. It seems that the antiatherosclerotic effect of vitamin D is at least partly attributed to the up-regulation of anti-inflammatory cytokines especially TGF- ß1.

Purification, Characterization and Comparison between Two New L-asparaginases from Bacillus PG03 and Bacillus PG04.

BACKGROUND: L-asparaginase has been used as a chemotherapeutic agent in treatment of lymphoblastic leukemia. In the present investigation, Bacillus sp. PG03 and Bacillus sp. PG04 were studied. METHODS: L- asparaginases were produced using different culture media and were purified using ion exchange chromatography. RESULTS: Maximum productivity was obtained when asparagine was used as the nitrogen source at pH 7 and 48 h after cultivation. New intracellular L-asparaginases showed an apparent molecular weight of 25 kDa and 30 kDa by SDS-PAGE respectively. These enzymes were active in a wide pH range (3-9) with maximum activity at pH 6 for Bacillus PG03 and pH 7 for Bacillus PG04 L-asparaginase. Bacillus PG03 enzyme was optimally active at 37 ˚C and Bacillus PG04 maximum activity was observed at 40˚C. Kinetic parameters km and Vmax of both enzymes were studied using L-asparagine as the substrate. Thermal inactivation studies of Bacillus PG03 and Bacillus PG04 L-asparaginase exhibited t1/2 of 69.3 min and 34.6 min in 37 ˚C respectively. Also T50 and ∆G of inactivation were measured for both enzymes. CONCLUSION: The results revealed that both enzymes had appropriate characteristics and thus could be a potential candidate for medical applications.

FoxP3 gene promoter polymorphism affects susceptibility to preeclampsia.

BACKGROUND: Preeclampsia (PE) is a multifactorial pregnancy disorder and is a major cause of maternal morbidity and mortality. Despite intense study, the pathophysiology of preeclampsia remains enigmatic. Recent studies have reported that regulatory T cells (Tregs) is linked with PE. It is well identified that FoxP3/Scurfin is involved in development and function of Tregs. However, the association between PE and the FoxP3 gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the FoxP3 may be related to PE. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the FoxP3 genes with sequence-specific primers (PCR-SSP) in 81 PE patients and 90 age-matched controls. RESULT: We identified significant difference of rs4824747 GG genotype frequency between the PE and control groups. Women with GG genotypes exhibited higher (OR=6.25, 95% CI=2.63-14.85; P<0.0001) risk of developing PE. None of the other investigated SNPs (rs2232365, rs3761547 and rs3761548) showed significant association with PE. CONCLUSION: We suggest that FoxP3 polymorphisms (rs4824747) could be a potential contributor for the development of PE in Iranian women.

Regulatory T-cells and preeclampsia: an overview of literature.

Regulatory T-cells (Tregs) are key players in successful pregnancy and their deficiencies are implicated in pregnancy complications such as preeclampsia (PE), but the results are inconsistent among studies. This study aims to compile an overview of the studies about the associations of Tregs and PE risk and to provide recommendations for future research. A sensitive search of three databases including PubMed, Scopus and Google scholar (from 1995 to January 9, 2015) identified 636 unique titles. An accurate process of study selection, data extraction and method qualification were independently conducted by authors on retrieved papers. Seventeen papers met the inclusion criteria and were included in quality assessment. Regarding the source of Tregs, 14 studies assessed Tregs in peripheral blood, 2 studies in peripheral blood and decidua and one study in peripheral blood and umbilical cord blood. Despite variation in the combinations of markers and other aspects of the studies designs, remarkable constancy in the results of studies that measured Tregs as CD4+FoxP3+ or CD4+CD25+FoxP3+ cells (but not CD4+CD25(high/low)FoxP3+ markers) was found, which in broad terms showed a shift towards fewer Treg cells in PE. This review revealed an association between lower percentage of circulating CD4+FoxP3+ or CD4+CD25+FoxP3+ Tregs and the risk of PE. Given the above issue and regarding the high consistency of studies on reduction of suppressive activity of Tregs in PE, we have proposed a model in which the Tregs deficiency is a reflection of immune endocrine imbalance, which reverses maternal tolerance and results in development of preeclampsia.