Expression and Alteration Value of Long Noncoding RNA AB073614 and FER1L4 in Patients with Acute Myeloid Leukemia (AML).

BACKGROUND: Numerous studies have probed the deregulation of the long noncoding RNA AB073614 and FER1L4, which have been discovered in a variety of cancers. However, the precise expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) remain elusive. Considering the involvement of the PI3K axis in AML pathogenesis, an investigation into the expression of AB073614 and FER1L4 targets of this pathway has been proposed, aiming to elucidate a potential mechanism underlying AML development. METHODS: The expression levels of lncRNA AB073614 and FER1L4 were assessed in 30 newly diagnosed AML patients and 12 healthy individuals using quantitative reverse transcription-polymerase chain reaction techniques. A statistical analysis was conducted to determine the association of AB073614 and FER1L4 expression levels with clinicopathological features. RESULTS: A significant upregulation of AB073614 was observed in AML patients compared to the control group (p < 0.05). Moreover, a notable increase in AB073614 expression levels coincided with a significant reduction in FER1L4 expression levels in AML samples (p < 0.05). The diagnostic value of these lncRNAs was validated using the receiver operating characteristic (ROC) curve and area under the curve (AUC) calculations. Sensitivity values of AB073614 and FER1L4 gene expression were 96.7% and 100%, respectively, using cut-off relative quantification of 1.045 and 0.770. Additionally, specificity values were observed to be 100%. CONCLUSIONS: The present study indicates that AB073614 and FER1L4 might serve as prognosis biomarkers in AML patients. However, further detailed examinations in this field are warranted. It is proposed that the likely mechanism of imbalanced PI3K and PTEN activity, triggered by the deregulation of AB073614 and FER1L4, may have a crucial role in AML pathogenesis. Any component of this pathway could potentially serve as a new target for more insightful treatment approaches.

Investigating Glenohumeral Joint Contact Forces and Kinematics in Different Keyboard and Monitor Setups using Opensim.

Background: The musculoskeletal complaints of the shoulder are prevalent in people who work with computers for a long time. Objective: This study aimed to investigate the glenohumeral joint contact forces and kinematics in different keyboards and monitor setups using OpenSim. Material and Methods: Twelve randomly selected healthy males participated in an experimental study. A 3×3 factorial design was used in which three angles were considered for the monitor and three horizontal distances for the keyboard while performing standard tasks. The workstation was adjusted based on ANSI/HFES-100-2007 standard to maintain a comfortable ergonomic posture for controlling confounding variables. Qualisys motion capture system and OpenSim were used. Results: The maximum mean range of motion (ROM) of both shoulders' flexion and adduction was observed when the keyboard was 15 cm from the edge of the desk, and the monitor angle was 30°. The maximum mean ROM of both shoulders' internal rotation was recorded for the keyboard at the edge of the desk. Peak forces for most right shoulder complex muscles were obtained in two setups. 3D shoulder joint moments were significantly different among nine setups (P-value<0.05). The peak anteroposterior and mediolateral joint contact forces were recorded for the keyboard at 15 cm and the monitor at zero angles (0.751 and 0.780 N/BW, respectively). The peak vertical joint contact force was observed for the keyboard at 15 cm and the monitor at 15° (0.310 N/BW). Conclusion: The glenohumeral joint contact forces are minimum for the keyboard at 8 cm and the monitor at zero angles.

A Retrospective Cytogenetic Abnormality in Pediatric Acute Lymphoblastic Leukemia: Report of 11 Years.

Background: Acute lymphoid leukemia (ALL) is the largest subset of hematologic malignancies, accounting for approximately 70%-80% of childhood leukemia, and is most common at age 4 years. The aim of this study was to define the frequency of chromosomal abnormalities in pediatric ALL. Materials and Methods: In this 11-year retrospective study, we investigated 99 patients which referred to our department due to ALL from 2010 to 2020. The age group of the patients ranged from 6 months to 14 years with a mean of 6.71 ± 4.09 years. Clinical and diagnostic findings were extracted from patients' medical records. Results: We showed cytogenetic abnormalities of 99 pediatric ALL patients, including 78 pre-B-ALL, 9 common B-ALL, and 12 T-ALL cases. The 5-year overall survival rate (OSR) and event-free survival (EFS) of all cytogenetic abnormalities (n = 99) were 48% and 43%, respectively. There was a significant relationship between the two cytogenetic abnormalities, hypodiploidy and t(9;22), with death (P < 0.05). On comparing the subjects with normal cytogenetics to the other cytogenetic abnormalities, EFS was significantly low for hypodiploidy (P = 0.0163, hazard ratio = 0.5308) and t(9;22) (P = 0.0131, hazard ratio = 0.4908), while other cytogenetic abnormalities did not have a statistically significant difference in EFS. Conclusions: Our results emphasized the importance of the cytogenetic findings in evaluating the survival outcomes, which allows identifying a variety of OSR and EFS, because some of the cytogenetic abnormalities may interfere with the death and prognosis.

Investigation of biological effects of chitosan magnetic nano-composites hydrogel.

The growing concern about microorganism infections, especially hospital-acquired infections, has driven the demand for effective and safe agents in recent years. Herein, novel nanocomposites were prepared based on layered double hydroxides (LDH NPs), Fe2O3nanoparticles (Fe2O3NPs), and chitosan hydrogel beads in different concentrations. The characteristics and composition of the prepared materials were investigated by various techniques such as XRD, FESEM, and FTIR. The results indicate that the nanocomposites are synthesized successfully, and each component is present in hydrogel matrixes. Then, their biomedical properties, including antibacterial, antifungal, and antioxidant activity, were examined. Our findings demonstrate that the antimicrobial activity of nanocomposites significantly depends on the concentration of each component and their chemical groups. It shows itself in the result of the inhibitory zone of all bacteria or fungi samples. The obtained results indicate that the nanocomposite of Chitosan-hydrogel beads with 20% LDH and Fe2O3(CHB-LDH-Fe2O3%20) and Chitosan-hydrogel beads based on 20% LDH (CHB-LDH%20) showed excellent antibacterial and antifungal properties against all tested bacteria and fungi (P ≤ 0.01). In addition, the antioxidant effects of the synthesized materials (especially CHB-LDH Fe2O3%20 and CHB-LDH%20) were investigated, showing high antioxidant efficacy against DPPH free radicals (P ≤ 0.01). According to our findings, we can say that these materials are promising biomaterials for inhibiting some infectious bacteria and fungi.

Investigating the Effect of Keyboard Distance on the Posture and 3D Moments of Wrist and Elbow Joints among Males Using OpenSim.

Musculoskeletal disorders (MSDs) of the upper extremities and computer use are common in modern societies, and both show a growing trend. This study was conducted to determine the posture and 3D moments of wrist and elbow joints at different keyboard distances on a desk. Twelve healthy right-handed male volunteers attended the motion analysis laboratory. A keyboard was placed at three different distances from the participants' bodies while performing a standard computer task. The workstation was adjusted according to ANSI/HFES-100-2007 standard for each participant to maintain a comfortable ergonomic posture for controlling confounding variables. Qualisys motion capture system, OpenSim (Ver. 4.1), and visual analog scale were used to collect and analyze the data. The highest levels of wrist flexion and radial deviation as well as elbow flexion and pronation were observed when the keyboard was at the edge of the desk. When the keyboard was 8 cm away from the edge of the desk, the right wrist flexion and radial deviation decreased 83% and 89%, respectively. In the left wrist, flexion and radial deviation decreased 94%. With increasing the distance of the keyboard from the edge of the desk, the right elbow flexion, pronation, and left elbow flexion decreased, 95%, 76%, and 85%, respectively. No significant difference was found for the left elbow pronation, wrist, and elbow joint moments, in the studied keyboard distances. However, a cut-off point has to be specified because large keyboard distances cause high extension and flexion of the limbs. The keyboard position relative to the body is an important parameter in computer work and has a significant impact on the posture of the upper extremities. A keyboard should be located at a distance that allows the upper extremities to remain in a neutral position so that the risk of MSDs is reduced.

Assessment of the association between TNIP1 polymorphism with clinical features and risk of systemic lupus erythematosus.

OBJECTIVE: Over the past decades, TNIP1 has been identified as a strong risk locus in multiple genome-wide association studies (GWAS), spanning multiple populations and various autoimmune diseases. TNIP1 is a polyubiquitin-binding protein that works as a physiological inhibitor of NF-κB and maintains immune homeostasis. Some studies have confirmed that TNIP1 is downregulated in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, for the first time, we evaluated the possible association between rs6889239 polymorphism in the TNIP1 gene with the risk and clinical characteristics of RA and SLE in the Iranian population. METHOD: In this case-control study, 115 patients with RA, 115 patients with SLE, and 115 unrelated healthy subjects were enrolled to estimate rs6889239 genotypes with real-time PCR high resolution melting (HRM) method. RESULTS: Our results demonstrated considerable associations between CC genotype and C allele of rs6889239 with augmented risk of SLE (OR for CC genotype= 2.23; 95%CI [1.175-4.307], OR for C allele= 1.84; 95%CI [1.254-2.720]). However, there was an insignificant association between genotypes and allele frequencies of rs6889239 with the occurrence risk of RA in the population under study (p > 0.05). Additionally, stratification analysis specified that the C allele in rs6889239 was linked with the incidence of renal involvement in SLE patients and lower age of onset in the RA group (p < 0.05). CONCLUSION: These findings propose a significant association between TNIP1 polymorphism and higher risk of SLE and some clinical characteristics of RA and SLE.

Novel insertion mutation in the PLA2G6 gene in an Iranian family with infantile neuroaxonal dystrophy.

BACKGROUND: Infantile neuroaxonal dystrophy is an autosomal recessive neurological disorder. Individuals with infantile neuroaxonal dystrophy experience progressive loss of vision, mental skills and muscular control, and other variable clinical signs. Pathogenic variants in the PLA2G6 gene, encoding phospholipase A2, are recognized to be the fundamental reason for infantile neuroaxonal dystrophy. This study aimed to detect pathogenic variant in a consanguine Iranian family with infantile neuroaxonal dystrophy. METHODS: The mutation screening was done by whole exome sequencing followed by direct Sanger sequencing. RESULTS: We identified a homozygous insertion mutation, NM_003560: c.1548_1549insCG (p.G517Rfs*29) in exon 10 of PLA2G6 in the patient. The parents were heterozygous for variant. CONCLUSIONS: Because of the clinical heterogeneity and rarity of infantile neuroaxonal dystrophy, whole exome sequencing is critical to confirm the diagnosis and is an excellent tool for INAD management.

The effect of Ccnb1ip1 insulator on monoclonal antibody expression in Chinese hamster ovary cells.

BACKGROUND: The increasing need for therapeutic monoclonal antibodies (mAbs) entails the development of innovative and improved expression strategies. Chromatin insulators have been utilized for the enhancement of the heterologous proteins in mammalian cells. METHODS AND RESULTS: In the current study the Ccnb1ip1 gene insulator element was utilized to construct a novel vector system for the expression of an anti-CD52 mAb in Chinese hamster ovary (CHO) cells. The insulator containing (pIns-mAb) and control (pmAb) vectors were generated and stable cell pools were established using these constructs. The expression level in the cells created with pIns-mAb vector was calculated to be 233 ng/mL, and the expression rate in the control vector was 210 ng/mL, which indicated a 10.9% increase in mAb expression in pIns-mAb pool. In addition, analysis of mAb expression in clonal cells established from each pool showed a 10% increase in antibody productivity in the highest mAb producing clone derived from the pIns-mAb pool compared to the clone isolated from pmAb pool. CONCLUSIONS: More studies are needed to fully elucidate the effects of Ccnb1ip1 gene insulator on recombinant therapeutic protein expression in mammalian cells. The combination of this element with other chromatin-modifying elements might improve its augmentation effect which could pave the way for efficient and cost-effective production of therapeutic drugs.

Differential expression of Hsa-miR-517a/b in placental tissue may contribute to the pathogenesis of preeclampsia

Objective: Preeclampsia (PE) is a pregnancy hypertensive disorder that affects both maternal and fetal health. Many studies have investigated possible mechanisms in the pathogenesis of PE although the role of the placenta is undeniable. Evaluation of placental-specific microRNAs may provide additional data about the pathogenic mechanism of PE. This study compared the expression levels of Hsa-miR-517a/b in placental tissues obtained from PE patients and healthy controls. Material and Methods: One hundred tissues were obtained from fetal and maternal sides of the placenta of PE patients and healthy controls. Expression analysis was performed using quantitative real-time polymerase chain reaction. Results: Hsa-miR-517a/b level was significantly decreased in PE compared to controls (expression ratio: 0.40; p=0.007). Down-regulation of Hsa-miR-517a/b was also detected in fetal-side placental samples when compared to maternal-side in PE (expression ratio: 0.33; p=0.04). Furthermore, decreased expression of Hsa-miR-517a/b was detected in fetal-side tissue from PE cases compared to fetal-side samples from healthy pregnancies (expression ratio: 0.36; p=0.03). In maternal-side placental samples the expression level did not differ between PE and healthy pregnancies (p=0.1). Conclusion: These results demonstrate a differential expression of Hsa-miR-517a/b within placentas in pregnancies affected by PE and between placentas from PE and healthy pregnancies. Further studies are required to investigate a possible role for Hsa-miR-517a/b in the pathogenesis of PE.

CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene.

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.

CYP24A1 expression analysis in uterine leiomyoma regarding MED12 mutation profile.

INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Contribution of long noncoding RNA HOTAIR variants to preeclampsia susceptibility in Iranian women.

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 included 250 preeclamptic women and 250 healthy women. The genotyping for rs920778 and rs874945 polymorphisms were performed using the TP-ARMS-PCR method. Results: HOTAIR rs920778 increased the risk of preeclampsia under the dominant and recessive inheritance patterns (OR = 4.84, 95% CI: 3.30-7.10, P < 0.0001; OR = 6.86, 95% CI: 3.51-13.42, P < 0.0001; respectively). Conclusion: This study confirmed the association of HOTAIR rs920778 polymorphism with preeclampsia in Iranian women. Further studies should be performed to confirm our findings.

Effects of kinesio tape on kinesiophobia, balance and functional performance of athletes with post anterior cruciate ligament reconstruction: a pilot clinical trial.

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 < 0.001). 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.

A homozygous missense mutation of WFS1 gene causes Wolfram's syndrome without hearing loss in an Iranian family (a report of clinical heterogeneity).

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.

The novel homozygous p.Asn197_Ser201del mutation in BTD gene is associated with profound biotinidase deficiency in an Iranian consanguineous family.

BACKGROUND: Biotinidase deficiency is an autosomal recessive inherited inborn error of biotin metabolism. Biotin as a water-soluble vitamin is the prosthetic group of biotin-dependent carboxylase enzymes, and by enhancing their function plays a key role in amino acid catabolism, fatty acid synthesis, and gluconeogenesis. Beyond its prosthetic group role, it has been recognized that biotin regulates the level of gene transcription in the eukaryotic cells, therefore any defect in these pathways causes a multisystem metabolic disorder characterized by neurological and cutaneous symptoms. METHODS AND RESULTS: We report the identification of a novel pathogenic variant in the BTD gene, c.528_542del15 (p.Asn197_Ser201del, UniProt P43251-1) in an Iranian consanguineous family with a severe form of the disease. The segregation analysis in the family was consistent with phenotype and the identified variant was predicated as a pathogenic mutation by the in-silico prediction tools. Computer structural modeling suggests the deleted amino acid residues are located near the biotinidase active site and disrupt the special conformations which are critical for the enzyme activity, and also N-glycosylation. CONCLUSIONS: This study further expands the mutation spectrum of the BTD gene underlying cause of profound biotinidase deficiency.

Silibinin treatment results in reducing OPA1&MFN1 genes expression in a rat model hepatic ischemia-reperfusion.

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.

Ectopic expression of CYP24A1 circular RNA hsa_circ_0060927 in uterine leiomyomas.

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.

Whole exome sequencing identified two homozygous ALMS1 mutations in an Iranian family with Alström syndrome.

Alström 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.

Investigation of CEBPA and CEBPA-AS Genes Expression in Acute Myeloid Leukemia.

BACKGROUND: The pathogenicity of acute myeloid leukemia (AML) is highly influenced by genetic alterations, such as chromosomal abnormalities. Additionally, aberrations in the mechanisms involved in gene expression have been identified to have a role in the development of AML. Contradictory evidence has been reported concerning the expression of the CEBPA gene in AML patients. Additionally, investigation into the expression of the CEBPA-AS gene has yet to be explored in AML patients. The aim of the present study was to investigate the relationship between the expression of the CEBPA and CEBPA-AS genes and AML in Iranian patients. METHODS: Using quantitative real-time PCR, the expression of the CEBPA and CEBPA-AS genes was examined in the peripheral blood samples of 58 patients with de novo adult AML, and in 20 healthy controls. RESULTS: Overall, CEBPA expression analysis showed a significant up-regulation in AML patients compared with healthy controls. Interestingly, a significant up-regulation of CEBPA was detected in the male AML patients. Significant CEBPA over-expression was observed in M0 (p-value=0.0001), M3 (p-value= 0.012) and M4 (p-value= 0.000) FAB subtypes. Our data has also demonstrated that CEBPA expression is up-regulated in favorable (p-value= 0.006) and adverse (p-value= 0.042) cytogenetic risk groups. In addition, the expression of CEBPA was significantly increased in AML patients with an abnormal karyotype. Ectopic expression of CEBPA-AS was detected in seven of the AML patients. CONCLUSION: Our study provides evidence for the up-regulation of CEBPA and the ectopic expression of CEBPA-AS in AML patients, suggesting that these two genes may play an important role in the pathogenesis of AML. The role of CEBPA and CEBPA-AS in AML patients should be further explored. This will offer potential opportunities for the development of novel treatment strategies.

An intron variant in the FLT1 gene increases the risk of preeclampsia in Iranian women.

Background: Preeclampsia is a hypertensive disorder that affects pregnancy, mother, and fetus. Pathogenesis of preeclampsia could be associated with the angiogenesis pathways. The vascular endothelial growth factor (VEGF) family is one of the important factors for normal pregnancy and angiogenesis. Genetic variations in the gene family members may play a role in the etiology of preeclampsia. We investigated the possible association between VEGFA gene rs3025039, and VEGFR1 (FLT1) gene rs722503 polymorphisms and preeclampsia in a sample of Iranian patients. Methods: Genotyping was performed in 395 women, including, 204 pre-eclamptic pregnant women and 191 healthy normotensive pregnant women by using the PCR-RFLP method. Results: The rs722503 polymorphism was associated with preeclampsia under the dominant model (P = 0.04, OR = 1.53, 95% CI: 1.03-2.27). No significant difference was observed for the rs3025039 alleles and genotypes in the studied groups. Conclusions: Based on our study, rs722503 polymorphism in the FLT1 gene may play an important role in susceptibility to preeclampsia.