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Preeclampsia (PE) is a major complication of pregnancy and remains a leading cause of neonatal and maternal mortality worldwide. Several studies have revealed that the incidence of preeclampsia is high in mothers who carried a fetus with Rubinstein-Taybi Syndrome due to the mutation in CREBBP. We aimed to compare the expression level of the CERBBP gene between preeclamptic and healthy placenta in our study. The expression level of CREBBP gene was evaluated in a total of one hundred placental biopsies from PE patients and healthy pregnant women after delivery using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the differential expression of CREBBP was assessed between the maternal and fetal sides of the placenta. Expression of the CREBBP gene was higher in preeclampsia patients compared with the controls (Fold change = 2.158; P = 0.018). Moreover, the gene expression was slightly higher in the fetal side of the placenta, although it was not significantly different (Fold change = 1.713, P = 0.254). Our findings show a role for CREBBP in the pathogenesis of PE. Due to the important role of CREBBP in angiogenesis and hypoxia, the gene may serve as a promising target in future studies.

Objective: To investigate the possible association of lncRNA HOTAIR rs920778 and rs874945 polymorphisms with preeclampsia risk in a sample from the Iranian population. Method: The study subjects in...

The mitochondrial damage has a pivotal role in triggering apoptosis and cell death. This study assessed the effect of silibinin on optical atrophy-1 (OPA1) and mitofusin-1 (MFN1) gene expression in liver tissue during hepatic warm ischemia-reperfusion (IR). Four groups of rats, eight rats each were designed: Vehicle: the rats received normal saline and encountered to laparotomy, Sili: silibinin (60 mg/kg) was administered to animals, IR: the rats received the normal saline and insulted by liver IR procedure, and IR + Sili: silibinin was injected to rats. All groups were subjected to the same process of injection of the solvent or silibinin (30 min before laparotomy or ischemia and immediately after the reperfusion), intraperitoneally (IP). After 3 h of reperfusion, blood and liver tissue samples were collected for future examinations. Our results showed no significant differences between the Vehicle and Sili groups in all assessed parameters. In IR + Sili, the increased serum levels of AST and ALT in comparison with the control group were markedly reduced by silibinin treatment. Silibinin lowered the elevated expression of OPA1 and MFN1 mRNAs in the IR group. Histology revealed silibinin could decline tissue degeneration compared to the IR group. Electron microscopy of control and silibinin groups showed no fusion of mitochondria and tissue degradation both of which were observed in the IR group. The extent of tissue destruction and mitochondrial fusion decreased significantly with silibinin treatment. Silibinin has a protective effect on liver cells against IR induced injuries by preserving mitochondrial membrane.

Background Anterior cruciate ligament trauma is one of the most common knee injuries in professional athletes. This study aimed to investigate the effects of kinesio taping on kinesiophobia, balance, and functional performance in athletes after anterior cruciate ligament reconstruction. Methods This randomized, placebo-controlled clinical trial was performed on 20 athletes with anterior cruciate ligament reconstruction (mean age 32.3 ± 6.2 years) at the time of return to sport. The subjects were randomly assigned to the kinesio tape (KT) group (n = 10) or placebo KT group (n = 10). While subjects under taped, the following outcomes were measured at baseline, 10 minutes after the intervention, and 2 days later. Kinesiophobia, balance, strength, and functional / agility performance were assessed by the Tampa Scale, Y balance test (YBT), single-leg hops, and 10-yard extremity functional test, respectively. Results The results did not show a significant difference between-group post-intervention differences in kinesiophobia (Mean between-group difference = − 6.30, 95% CI = − 4.35 to 1.42, P-value = 0.17). Likewise, no significant statistical difference was observed between two study groups in terms of YBT scores (Mean between-group difference ranged over = − 6.30, 95% CI = − 1.1 to 4.7, the effect sizes ranged over = 0.01 to 0.31), P-value > 0.05), Single Leg Hop (Mean between-group difference = − 0.48, 95% CI for difference ranged over = − 10.3 to 9.3, effect size = 0.001, P-value = 0.918), and 10 Yard test scores (Mean between-group difference = − 0.30, 95% CI = (− 1.3 to 0.75), effect size = 0.02, P-value = 0.55) at 2 days after the KT. In the KT and placebo KT groups, RMANOVA indicated that the differences in all variables scores were significant over time with large effect sizes (effect size ranged over = 0.94–0.99; all P-value Conclusion This study gives no support for any beneficial effect of kinesio taping on the reduction of kinesiophobi or improvement of balance score and functional performance in athletes with post anterior cruciate ligament reconstruction. Trial registration This study was registered in the Iranian Clinical Trial Center with the code IRCT20190130042556N1, registered 12 February 2019.

Background Wolfram's syndrome (WFS) is a hereditary (autosomal recessive) neurodegenerative disorder. The clinical features are related to diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) with other variable clinical manifestations. Pathogenic variants in the WFS1 gene, encoding wolframin, are known to be the main cause of Wolfram's syndrome. In this study, we present the clinical and genetic characteristics of two WFS patients from an Iranian family. Methods The mutation screening was performed by polymerase chain reaction (PCR) followed by direct Sanger sequencing of all exons from two affected WFS. Results The complete Sanger sequencing of the WFS1 gene detected a homozygous missense variant, c.2207G>A (p.Gly736Asp), in the eighth exon of the WFS1 gene. Both cases developed all the major symptoms of the disease, interestingly, except hearing loss. Conclusions Because of the rarity and clinical heterogeneity of WFS, the molecular genetic assay is essential to confirm the diagnosis and management of the WFS patients.

Uterine leiomyoma (ULM) is the most common gynecological tumor. Recent studies have revealed the role of hypovitaminosis D as a major risk factor in the disease development. CYP24A, a mitochondrial enzyme that catalyzes the degradation of 1,25(OH)2D3, is reported to be over-expressed in several human cancers. In this study, we aimed to investigate the expression level of CYP24A1 in leiomyoma samples compared with the adjacent tissues regarding the MED12 mutation profile. In the present study, 61 ULMs and adjacent tissue samples were collected from 51 women undergoing hysterectomy and myomectomy. The samples were Sanger sequenced for MED12 mutation, and the expression level of CYP24A1 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The results demonstrated that CYP24A1 gene was ectopically expressed in 18% of uterine leiomyoma tissues, although this expression was independent of the MED12 mutation profile. The findings of the present study support current evidence that dysregulation of vitamin D signaling and metabolic pathways may be involved in at least some subtypes of ULMs.

Background As a novel class of non‐coding RNAs, the role of circular RNAs (circRNAs) in tumor biogenesis and progression has been proved in a number of human tumors; however, up to now, the relation between circRNAs and uterine leiomyomas (ULM) remains unclear. Methods In this study, we have estimated the expression level of CYP24A1 hsa_circ_0060927 in uterine leiomyoma and adjacent tissues considering the mediator complex subunit 12 gene (MED12) mutation profile by quantitative real‐time polymerase chain reaction (qRT‐PCRs). Results Using Sanger sequencing method, somatic mutations in the MED12 exon 2 were detected in 14 (35.90%) ULM samples, including 10 (71.43%) missense mutations and 4 (28.57%) in‐frame deletions. Our results revealed that hsa_circ_0060927 was ectopically expressed in 33.33% of ULM tissues; although, this expression was independent of the MED12 mutation profile in the ULM samples. Conclusions Present results provide primary evidence for the role of circular RNAs in the leiomyoma development; however, further studies are essential to confirm the importance of these molecules as potential biomarkers for diagnosis and/or prognosis in ULM.

Introduction Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. Objectives We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. Methods In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. Results The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model (P=0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups (P=0.009; OR =2.48; 95% CI, 1.25-4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Conclusion Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations.

Pre-eclampsia (PE) is a multifactorial pregnancy disorder, with serious consequences for both the mother and the fetus. Despite intense studies, the pathophysiology of PE remains enigmatic. Previous studies suggested that Treg dysfunction is involved in the pathogenesis of PE. We hypothesized that functional variants of the FOXP3 gene might be associated with PE via dysregulation of Treg cells. Of the 276 subjects, we genotyped three variants of FOXP3 by PCR-RFLP and Tetra ARMS-PCR methods. The genotypic frequencies of rs2232365 were found to be protective from the development of PE under codominant [odds ratio (OR) 0.49, 95 percent confidence interval (CI) 0.28-0.87, p-value = 0.043], dominant [odds ratio (OR) 0.54, 95 percent confidence interval (CI) 0.32-0.94, p-value = 0.027] and over dominant [odds ratio (OR) 0.57, 95 percent confidence interval (CI) 0.35-0.92, p-value = 0.02] models. Moreover, the rs3761548 conferred a risk of PE in recessive model [odds ratio (OR) 2.05, 95 percent confidence interval (CI) 1.08-3.88, p-value = 0.025]. However, no mutation was detected in FOXP3 exon2 in any of the studied samples. Based on our results, thought that FOXP3 variants may be an important contributor for the progression of PE in Iranian women.

Background: Studies collectively imply that the reciprocal link has no effect on walking when using reciprocating gait orthoses (RGOs). There may be differences between the 2 configurations of the RGO (eg, isocentric reciprocating gait orthosis [IRGO] and IRGO without reciprocating link), but the specific benefits and problems encountered in their use must be understood. Purpose: To highlight more evidence for the mechanical function of the reciprocal link in RGOs used for walking by individuals with spinal cord injury (SCI). Methods: Nine people with SCI participated in this study. Gait analysis was performed in 2 conditions (walking with IRGO and walking with IRGO without reciprocating link) in a random order. The Vicon digital capture system was used to obtain kinematic data. Results: There were significant differences between each orthotic configuration in terms of speed of walking (p = .029), step length (p = .048), hip joint range of motion (ROM) (p ≤ .001), and lateral and vertical compensatory motions (p ≤ .001). There was no significant difference between each orthotic configuration in cadence (p = .162). Conclusion: The reciprocating link in IRGO improved the walking parameters in SCI patients.

Background: Preeclampsia is a hypertensive disorder that affects pregnancy, mother, and fetus. Pathogenesis of preeclampsia could be associated with the angiogenesis pathways. The vascular ...

Background Acute myeloid leukemia (AML) is derived from primitive hematopoietic stem cells or progenitor cells due to genetic variations such as chromosomal abnormalities and molecular alterations. Mutations in the RTK-BRAF genes are involved in leukaemogenesis. Few reports simultaneously concerning the mutation alteration of the RTK-BRAF genes have been publicized in AML subjects. The current study aimed to screen the mutations of RTK-BRAF genes in Iranian de novo adult AML subjects. Methods Mutations of RTK-BRAF genes were investigated in bone marrow specimens from 58 patients with de novo adult AML. High-Resolution Melt (HRM) curve analysis was performed for the identification of FLT3-ITD and D835 mutations. Mutations in the NPM1 (exon12), BRAF (exons11 and 15), PTPN11(exons 3 and 13) and c-FMS (exon22) were detected using Sanger sequencing method. Results Totally, FLT3 and NPM1 mutations were found in 34.48% and 25.86% of AML patients, respectively. Moreover, mutations in the FLT3 and NPM1 genes were significantly higher in normal karyotype AML subjects (52.38% and 38%, respectively) than patients with abnormal karyotype (p-value = 0.001 and p-value = 0.002, respectively). No mutations were detected in other RTK-BRAF genes. Conclusion According to the findings of this research, in addition to the chromosomal abnormalities in the patients with acute myeloid leukemia, FLT3 and NPM1 mutations were the most recurrent genetic alterations. Identification of these alterations may help to choose appropriate treatment and improve the patients' outcome.

UNLABELLED Acute coronary syndrome (ACS) is the most serious form of coronary artery disease. Inflammatory processes participate in different stages of this disorder. FOXP3 gene plays an important role for the development and function of regulatory T cells. Consequently, the expression level and polymorphisms of this gene have been studied in many immune related diseases. In the present study, we analysed the expression of FOXP3 as well as the association between two variants in this gene (rs3761548A/C and rs5902434del/ATT) and occurrence of ACS in Iranian patients. FOXP3 expression analysis showed a significant decrease in patients with ACS compared with controls (P = 0.029). In addition, a significant decrease has been detected in female patients compared with normal female subjects (P = 0.020). No significant change has been observed in FOXP3 expression in male patients compared with normal male subjects. In addition, no difference has been detected between ACS and normal subjects in combined genotype frequencies of both polymorphisms and the allele frequencies of rs5902434. However, rs3761548 C allele was more prevalent in controls compared with patients with ACS (P = 0.024). Consequently, our data demonstrated that FOXP3 expression is markedly decreased in female patients with ACS, which highlight the role of immune responses in plaque destabilization in such patients. Copyright © 2016 John Wiley & Sons, Ltd. SIGNIFICANCE PARAGRAPH Considering the role of immune system in different stages of acute coronary syndrome (ACS), we evaluated the expression of FOXP3 gene as a master regulator of immune response in these patients compared with normal subjects. We detected a significant down-regulation of this gene in patients with ACS. Such decreased expression was more prominent in female patients, which implies the role of immune responses in plaque destabilization in such patients.

Alstrom syndrome (AS) is a rare monogenic multi-system ciliopathy disorder with cardinal features, including cone-rod dystrophy, sensory neural hearing loss, metabolic dysfunctions and multiple organ failure caused by bi-allelic mutations in a centrosomal basal body protein-coding gene known as ALMS1. This study aimed to identify pathogenic mutations in a consanguineous Iranian family with AS. Next-generation sequencing was performed on the genomic DNA obtained from a 12 years old girl with AS. According to the bioinformatics analysis, computational modelling and segregation of variants, we identified two homozygous mutations close together in exon 8 of ALMS1 in the patient, including c.7262 G > T and c.7303-7305delAG. The clinically normal parents were heterozygous for both mutations. These mutations have a very rare frequency and only reported in the heterozygous state in the public genomic databases. Overall, due to the large size of the ALMS1 gene and clinical similarity with other ciliopathies and genetic disorders, whole exome sequencing can be useful for the identification of pathogenic mutations and the improvement of AS clinical management.

The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk factors that are important in the development of the disease. Therefore, the exact etiology and pathogenesis of preeclampsia remains unclear. It is suggested that inappropriate regulation of the renin–angiotensin system (RAS) is a risk factor for hypertension during pregnancy. The angiotensin I-converting enzyme (ACE) serum level, a key component of the RAS, affects the blood pressure. It is hypothesized that the ACE gene polymorphisms contribute to preeclampsia development. In a case–control study containing 296 subjects (165 PE patients and 131 normotensive controls), we aimed to examine the association of the ACE gene I/D and rs4343 polymorphisms with preeclampsia in Iranian women. Genotyping for rs4343 and ACE I/D polymorphisms was performed by using TP-ARMS-PCR and conventional PCR, respectively. The rs4343 G allele frequency was higher in the case group (OR = 1.90, 95% CI, 1.37–2.65; P = 0.0001). Besides, a significant difference was detected for the genotype frequencies between the studied groups under dominant (OR = 3.94, 95% CI, 2.05–7.56; P

Genes involved in piwi-interacting RNAs (piRNAs) pathway have an essential role in spermatogenesis. HIWI and TDRD proteins are critical for piRNA biogenesis and function. Therefore, Mutations and polymorphisms in HIWI and TDRD genes may play role in male infertility. The aim of the present study was to investigate the role of HIWI2 rs508485 (T>C) and HIWI3 rs11703684 (C>T) polymorphisms and mutational analysis of TDRD5 gene in idiopathic non-obstructive azoospermia in a case-control study including 226 non-obstructive azoospermia patients and 200 fertile males. Genotyping for both polymorphisms was performed using Tetra-Primer ARMS PCR. Mutation analysis of TDRD5 gene was done using multi-temperature single strand conformation polymorphism technique (MSSCP). The frequency of rs508485TC genotype was significantly different in the studied groups (P = 0.0032; OR = 2.12; 95% CI, 1.29–3.48). In addition, the genotype frequencies showed a significant difference under dominant model (P = 0.005; OR = 2.79; 95% CI, 1.22–3.13). No mutation was detected in the Tudor domain of the TDRD5 in the studied patients. In conclusion, we provide evidence for association between genetic variation in the HIWI2 gene and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway genes variants can be considered as risk factors for male infertility.

Background: Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS). MS is one of the most common cause of neurological impairment at a young age with a complex etiology. The forkhead/winged helix (FOXP3) gene encodes a transcription factor that plays an important role in the working and progress of regulatory T cells. Loss of the FOXP3 function impairs the suppressor activity of regulatory T (T-reg) cells, which have been reported in MS patients. Objectives: To determine whether rs2232365 and rs3761548 polymorphisms of FOXP3 are associated with the risk of MS in an Iranian population. Patients and Methods: In this case-control study, a total of 384 samples consisting of 190 MS patients and 194 unrelated healthy subjects from the Iranian population were recruited between December 2014 and September 2015. The patients were diagnosed by a neurologist based on McDonald’s criteria. The control group had no history or presence of autoimmune diseases. The polymorphisms were genotyped using tetra-ARMS PCR and PCR-restriction fragment length polymorphism (RFLP) techniques. Results: The Rs2232365 G allele was significantly associated with an increased risk of MS (P = 0.0068). In contrast, the allele and genotype frequencies of rs3761548 was not significantly different between the case and control groups (P > 0.05). Conclusions: The functional variant of the FOXP3, rs2232365 A/G, may be considered a substantial risk factor for MS.