Alihossein Saberi | Ahvaz Jundishapur University of Medical Sciences (original) (raw)

Papers by Alihossein Saberi

BMC Bioinformatics, Oct 1, 2022

BackgroundWe used a hybrid machine learning systems (HMLS) strategy that includes the extensive s... more BackgroundWe used a hybrid machine learning systems (HMLS) strategy that includes the extensive search for the discovery of the most optimal HMLSs, including feature selection algorithms, a feature extraction algorithm, and classifiers for diagnosing breast cancer. Hence, this study aims to obtain a high-importance transcriptome profile linked with classification procedures that can facilitate the early detection of breast cancer.MethodsIn the present study, 762 breast cancer patients and 138 solid tissue normal subjects were included. Three groups of machine learning (ML) algorithms were employed: (i) four feature selection procedures are employed and compared to select the most valuable feature: (1) ANOVA; (2) Mutual Information; (3) Extra Trees Classifier; and (4) Logistic Regression (LGR), (ii) a feature extraction algorithm (Principal Component Analysis), iii) we utilized 13 classification algorithms accompanied with automated ML hyperparameter tuning, including (1) LGR; (2) Support Vector Machine; (3) Bagging; (4) Gaussian Naive Bayes; (5) Decision Tree; (6) Gradient Boosting Decision Tree; (7) K Nearest Neighborhood; (8) Bernoulli Naive Bayes; (9) Random Forest; (10) AdaBoost, (11) ExtraTrees; (12) Linear Discriminant Analysis; and (13) Multilayer Perceptron (MLP). For evaluating the proposed models' performance, balance accuracy and area under the curve (AUC) were used.ResultsFeature selection procedure LGR + MLP classifier achieved the highest prediction accuracy and AUC (balanced accuracy: 0.86, AUC = 0.94), followed by an LGR + LGR classifier (balanced accuracy: 0.84, AUC = 0.94). The results showed that achieved AUC for the LGR + LGR classifier belonged to the 20 biomarkers as follows: TMEM212, SNORD115-13, ATP1A4, FRG2, CFHR4, ZCCHC13, FLJ46361, LY6G6E, ZNF323, KRT28, KRT25, LPPR5, C10orf99, PRKACG, SULT2A1, GRIN2C, EN2, GBA2, CUX2, and SNORA66.ConclusionsThe best performance was achieved using the LGR feature selection procedure and MLP classifier. Results show that the 20 biomarkers had the highest score or ranking in breast cancer detection.

Journal of pediatric nephrology, May 5, 2014

Renal tubular acidosis (RTA) is a rare genetic disorder. It has four clinical types, and type 3 d... more Renal tubular acidosis (RTA) is a rare genetic disorder. It has four clinical types, and type 3 demonstrates a mixed pattern of tubular dysfunction. The causative gene for type 3 RTA (CAII) is located on the 8q22 locus and encodes a protein called carbonic anhydrase II. In this study, we analyzed the entire exons and flanking regions of the CAII gene in a child suffering renal tubular acidosis with an autosomal recessive pattern that was diagnosed with type3 RTA. DNA was extracted from the blood sample of the patient and his parents by the salting out extraction method. The exons and flanking regions of the CAII gene were amplified using polymerase chain reaction (PCR). We performed exon direct sequencing by forward and reverse primers, which were designed by primer3 program. No mutation was found following the screening of the entire coding sequence of the CAII gene. It is likely that another gene might be involved in this case. In other words, other types of RTA have to be considered.

PubMed, May 31, 2023

Objective: The embryo implantation includes a complex sequence of signaling events, comprising nu... more Objective: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. Methods: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. Results: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. Conclusions: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.

Journal of Mazandaran University of Medical Sciences, Aug 10, 2021

Background and purpose: Hyperlipidemia is one of the main risk factors for coronary artery diseas... more Background and purpose: Hyperlipidemia is one of the main risk factors for coronary artery disease and is defined as abnormal elevation of lipids or lipoproteins in the blood. Pcsk9 is the ninth member of the proprotein convertase family that binds to the LDLR on the surface of the hepatocyte, leading to degradation of LDLR in lysosomes which could cause hyperlipidemia. The present study aimed to analyze the methylation status of pcsk9 promoter in patients with hyperlipidemia. Materials and methods: This case-control study was conducted in 50 patients with hyperlipidemia and 50 healthy controls. DNA isolation from whole blood was performed using salting out procedure. Promoter methylation of the Pcsk9 gene was analyzed by methylation-specific PCR (MSP). Ten MSP products were sequenced to confirm the data obtained. Results: According to MSP results, methylation pattern of pcsk9 gene promoter displayed an unmethylated status among the patients and control individuals. In other words, no methylation was seen in case and control samples. Conclusion: The current study showed no significant association between PCSK9 methylation pattern and blood lipid profile level in case group and control group.

Research Square (Research Square), Sep 7, 2022

Background:Spinal muscular atrophy (SMA) is a rare autosomal recessive inherited neuromuscular di... more Background:Spinal muscular atrophy (SMA) is a rare autosomal recessive inherited neuromuscular disease with about 1:6000 to 1:10,000 in newborns. Objectives:To evaluate the copy number variation of SMN1 and SMN2 genes between two generations, we experimented on 221 core families, including 221 patients and their parents (n=442). Materials & methods: Before sample collection, all cases were subjected to clinical diagnosis, electromyography, and nerve conduction velocity test. Moreover, DNA samples were analyzed by multiplex ligation-dependent probe ampli cation. Results: In this study, 92.7% of patients' SMN1 deletions were homozygous, whereas 7.3% of the SMN1 deletions were heterozygous. On the other hand, 92.9% of the parents had one copy of SMN1, and the remaining had two copies of SMN1. Since SMN2 has a disease-modifying role, accurate determination of SMN2 copy number can be helpful in the case of prognosis and genotype-phenotype correlation. The average SMN copies from parents represent the copy number in the parent's generation. Evaluations showed a negative correlation between the copy number of SMN1 and SMN2in children and their parents. Besides, when the average of SMN2 copy numbers was two in the parent's generation, 81% of the children were type I, and the rest were Type II/III. Also, in cases with three or more SMN2copy numbers in parents, approximately 90% of children were either type II or III. Conclusion: Accordingly, there is a possibility that the SMN2 copy numbers in parents could predict the disease severity in the next generation.

Scientific Reports, Mar 22, 2022

We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of pat... more We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of patients with Hb H disease. Molecular characterization of alpha-thalassemia was performed. We identified 120 patients with Hb H disease. Of these patients, 35 (29.16%) had deletional form of Hb H disease, and 85 (70.83%) had different form of non-deletional Hb H disease. The most frequently observed Hb H genotypes were-Med /-α 3.7 in 33 patients (27.5%), α CD19(-G) α /αCD19(-G) α in 25 cases (20.83%), α polyA2 α/α polyA2 α in 15 (12.5%), and α polyA1 α/α polyA1 α in 13 (10.83%) respectively. The probability of receiving at least one transfusion blood in deletional form was observed in 3 of 35 (8.57%) patients which just seen in 3 of 33 (9%) patients with-Med /-α 3.7 genotype. This form was also observed in 8 of 85 (9.4%) patients in non-deletional Hb H diseases which five of them had Med deletion in compound with alpha globin point mutations. Nondeletional Hb H disease was more severe than deletional Hb H disease requiring more blood transfusions. We can recommend that Med deletion in compound with alpha-globin point mutations, polyA1 and constant spring in homozygous form needs to be taken into consideration when offering counseling to high-risk couples. Alpha thalassemia is one of the most common monogenic disorders in the Mediterranean region, Middle East and East and Southeast Asia, as well as in countries with migration from these regions 1,2. The clinical manifestations of alpha globin abnormalities vary from the silent carrier state, in which only one α-globin gene is deleted, to fatal hydrops fetalis, in which all four α-globin genes are missing 3. Hemoglobin H (Hb H) disease is caused by the loss of three α-globin genes, when there is only one functional alpha globin gene the patient produce a form of hemoglobin (Hb) composed of four β-chain (β4) called Hb H 4. The clinical severity of patients with Hb H disease is variable, even in the presence of similar genotype, which is probably due to genetic and environmental modifiers 5. More than 95% of α-thalassemia syndromes are caused by deletional abnormalities while the rest result from point mutations 6. Hb H patients also have been classified as mild, intermediate or severe phenotypes. Mild phenotype included the patients, who diagnosed above 4 years of age, Hb levels above 9.0 g/dl, transfusion-independent, normal growth, minimal bone changes and slight splenomegaly. Intermediate phenotype included patients diagnosed between 2 ± 4 years, Hb more than 8.0 g/dl, transfusion-independent, with mildly impaired growth, some bone abnormalities and moderate splenomegaly. Severe phenotype included patients with severe anemia, Hb less than, 8.0 g/l, needing frequent or occasional transfusions. Hb H Patients with severe phenotype had impaired growth, moderate to severe bone changes and splenomegaly 7. There are two types of Hb H disease, deletional and non-deletional. The first type is the most common form of Hb H disease, is caused by compound heterozygosity with a double α-globin gene deletion on one allele and a single α-globin gene deletion on the other allele (16p13.3). Second type is the non-deletional form of Hb H disease which at least one of the genetic abnormalities was non-deletional 8. Non-deletional Hb H disease is

Jundishapur Scientific Medical Journal, Jan 21, 2018

Majallah-i taḥqīqāt-i ̒ulūm-i pizishkī-i Zāhidān, May 31, 2015

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common gene... more Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders. Genetic studies have demonstrated an important allelic variability among patients but very few data are known about the genetic variation in Iranian populations. Case Presentation: In this study, in order to verify the ADPKD in a patient with some clinical symptoms and study the variations of the PKD1 gene for the first time in Iranian population, the PKD1 gene was entirely sequenced. Coding exons analysis of PKD1 by exon direct sequencing was performed. Molecular genetic testing found a novel mutation in the patient. Conclusions: It was a missense mutation CAT > GAT at position 3311 in exon 30 of PKD1. CAT > GAT causes the conversion of amino acids histidine to argenine and change the transmembrane domain and proper function of the polycystin 1 protein.

PubMed, Sep 1, 2017

Introduction: Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose... more Introduction: Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose per fraction through complex treatment techniques. The increased complexity leads to longer dose delivery times for each fraction. The purpose of this study is to investigate the impact of prolonged fraction delivery time with high-dose hypofractionation on the killing of cultured ACHN cells. Methods and materials: The radiobiological characteristics and repair half-time of human ACHN renal cell carcinoma cell line were studied with clonogenic assays. A total dose of 20 Gy was administered in 1, 2 or 3 fractions over 15, 30 or 45 min to investigate the biological effectiveness of radiation delivery time and hypofractionation. Cell cycle and apoptosis analysis was performed after 3-fraction irradiation over 30 and 45 min. Results: The α/β and repair half-time were 5.2 Gy and 19 min, respectively. The surviving fractions increased with increase in the fraction delivery time and decreased more pronouncedly with increase in the fraction number over a treatment period of 30 to 45 min. With increase in the total radiation time to 30 and 45 min, it was found that with the same total dose, 2- and 3-fraction irradiation led to more cell killing than 1-fraction irradiation. 3-fraction radiation induced G2/M arrest, and the percentage of apoptotic cells decreased when the fraction delivery time increased from 30 min to 45 min. Conclusion: Our findings revealed that sublethal damage repair and redistribution of the cell cycle were predominant factors affecting cell response in the prolonged and hypofractionated irradiation regimes, respectively.

OBM Genetics

Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited... more Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited by mutations in MEFV. These mutations can affect the dysregulation of inflammatory processes in the human body and lead to fever and pain in the chest and abdomen. Many known missense mutations in MEFV are linked to FMF disease. Mutations in MEFV in most cases are located on the short arm of chromosome 16 and can impair the function of the pyrin protein. In this research, we aimed to examine the entire exons of MEFV for 13 cases (8 females and 5 males) with FMF diagnosis from Southwest Iran. Hence, we amplified and sequenced the exons of MEFV and then, in-silico analysis of detected changes was applied to estimate the probability of pathogenicity for the identified variants. Finally, we found five single nucleotide substitutions, including M694V (c.2080A>G), R202Q (c.605G>A), E447G (c.1430A>G), E148Q (c.442G>C), and V726A (c.2177T>C), in the under-represented patients. Th...

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer ... more Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair...

Supplementary Data from Multiple Repair Pathways Mediate Tolerance to Chemotherapeutic Cross-link... more Supplementary Data from Multiple Repair Pathways Mediate Tolerance to Chemotherapeutic Cross-linking Agents in Vertebrate Cells

Iranian biomedical journal

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common gene... more Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 (16p13.3, 46 exons) and PKD2 (4q21, 15 exons). Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. Methods: In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. Results: Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel...

Cancer Letters, 1994

An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying ... more An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying the possibility of induction of adaptive response to various doses of radiation following treatment with chemotherapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D (ACT-D) at 10 micrograms/kg body weight (therapeutic dose range) were injected intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various doses from 1-4 Gy was carried out at a dose rate of 45 cGy/min. Animals were killed at 24, 36 and 48 h post-irradiation. The results obtained in this study clearly indicate a significant difference for radiation induced micronuclei (MN) in polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range used. When used in combination with radiation, neither ACT-D nor BLM-S caused a synergistic or additive effect. Irradiated animals showed a higher incidence of micronuclei formation in the presence of ACT-D and BLM-S. However, in both cases, the number of MN induced in PCEs was less than the sum of MN induced by radiation and ACT-D or BLM-S alone. The effect of combined treatment was reduced by a factor of 1.5 for BLM-S and greater than 1.5 for ACT-D treated animals. These observations indicate that although a small amount of ACT-D or BLM-S reaches the bone marrow cells via the circulation, these drugs might produce effects which make bone marrow cells resistant to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal hemopoeitic tissue.

Neurological Sciences, 2021

Parkinson’s disease (PD) is known as one of the most common degenerative disorders related to the... more Parkinson’s disease (PD) is known as one of the most common degenerative disorders related to the damage of the central nervous system (CNS). This brain disorder is also characterized by the formation of Lewy bodies in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta (SNc), which consequently leads to motor and non-motor symptoms. With regard to the growing trend in the number of cases with PD and its effects on individuals, families, and communities, immediate treatments together with diagnostic methods are required. In this respect, long non-coding ribonucleic acids (lncRNAs) represent a large class of ncRNAs with more than 200 nucleotides in length, playing key roles in some important processes including gene expression, cell differentiation, genomic imprinting, apoptosis, and cell cycle. They are highly expressed in the CNS and previous studies have further reported that the expression profile of lncRNAs is disrupted in human diseases such as neurodegenerative disorders. Since the levels of some lncRNAs change over time in the brains of patients with PD, a number of previous studies have examined their potentials as biomarkers for this brain disorder. Therefore, the main purpose of this study was to review the advances in the related literature on lncRNAs as diagnostic, therapeutic, and prognostic biomarkers for PD.

British Journal of Medicine and Medical Research, 2016

Aims: To examine simultaneous effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on w... more Aims: To examine simultaneous effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on weight gain in diet induced obese rats. Study Design: Experimental study. Place and Duration of Study: Department of Nutrition, Faculty of Para-Medical Sciences, Ahvaz Jundishapur University of Medical Sciences (January 2014 to January 2015). Methodology: Forty male Wistar rats were randomly divided into two groups: Normal fat diet Original Research Article Nazari et al.; BJMMR, 12(1): 1-8, 2016; Article no.BJMMR.21609 2 (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group maintained HFD and was subdivided into 4 categories: Corn Oil group, 500 mg CLA, 200 mg LC, and 500 mg CLA+ 200 mg LC (all doses per kg body weight), which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. SPSS Version 16 was used for statistical analysis. Results: At the end of eighth week, a significant difference in weights was observed between HFD (295.43±5.36 gr) and NFD (246.38±6.48 gr) group. After four weeks, LC significantly reduced weight gain by 7.5% (P = .047). Trend of weight gain in CLA and LC + CLA groups were decelerated (24 and 25 gr respectively), but it was statistically insignificant (P = .08, .12 respectively). Conclusion: Findings of this experimental study showed that a high fat diet led to obesity and combined LC and CLA could decelerate weight gain to some extent. However, it needs further work to validate reliability in human.

Molecular Genetics & Genomic Medicine

Biomedical Research, 2018

Prenatal diagnosis of chromosomal abnormalities is an important challenge for pregnancy managemen... more Prenatal diagnosis of chromosomal abnormalities is an important challenge for pregnancy management has relied on conventional cytogenetic analysis of cultured amniotic fluid, chorionic villi, or fetal blood for a long time. New molecular methods included FISH and QF-PCR on uncultured amniotic fluid or chorionic villi have been applied recently for the rapid aneuploidies detection in chromosomes 13, 18, 21, X and Y. Both molecular methods are quicker than Karyotype as conventional cytogenetic technique. The advantages of QF-PCR include detection of trisomy, mosaicism and maternal cell contamination. This technique is more cost effective, less labor-intensive and more suitable for large sample numbers in comparison to FISH. FISH is a robust method and extensively validated. It detects mosaicism and trisomy. Herein we aimed to assess prenatal diagnosis of aneuploidies in chromosomes 13, 18, 21, X and Y. For this aim, amniotic fluid samples have collected for analysis of common chromosomal aneuploidies using Karyotype, FISH and QF-PCR methods. 69 samples have obtained by amniocentesis from 15 th-18 th week of pregnancies and subjected for comparative analysis by three techniques: FISH, QF, and Karyotype with the same accuracy concerning the detection of trisomy 13, 18, 21, and sex chromosomes X and Y. We conclude that molecular techniques are rapid-reliable methods for analysis of chromosome number in uncultured amniotic fluid. Nevertheless, QF-PCR and FISH are an alternative option, if timing is a limiting factor. This report in line with previous studies emphasizes the importance of molecular techniques for the prenatal identification of the numerical chromosomal abnormalities and ultimately management of pregnancies saving patients from anxiety.

BMC Bioinformatics, Oct 1, 2022

BackgroundWe used a hybrid machine learning systems (HMLS) strategy that includes the extensive s... more BackgroundWe used a hybrid machine learning systems (HMLS) strategy that includes the extensive search for the discovery of the most optimal HMLSs, including feature selection algorithms, a feature extraction algorithm, and classifiers for diagnosing breast cancer. Hence, this study aims to obtain a high-importance transcriptome profile linked with classification procedures that can facilitate the early detection of breast cancer.MethodsIn the present study, 762 breast cancer patients and 138 solid tissue normal subjects were included. Three groups of machine learning (ML) algorithms were employed: (i) four feature selection procedures are employed and compared to select the most valuable feature: (1) ANOVA; (2) Mutual Information; (3) Extra Trees Classifier; and (4) Logistic Regression (LGR), (ii) a feature extraction algorithm (Principal Component Analysis), iii) we utilized 13 classification algorithms accompanied with automated ML hyperparameter tuning, including (1) LGR; (2) Support Vector Machine; (3) Bagging; (4) Gaussian Naive Bayes; (5) Decision Tree; (6) Gradient Boosting Decision Tree; (7) K Nearest Neighborhood; (8) Bernoulli Naive Bayes; (9) Random Forest; (10) AdaBoost, (11) ExtraTrees; (12) Linear Discriminant Analysis; and (13) Multilayer Perceptron (MLP). For evaluating the proposed models' performance, balance accuracy and area under the curve (AUC) were used.ResultsFeature selection procedure LGR + MLP classifier achieved the highest prediction accuracy and AUC (balanced accuracy: 0.86, AUC = 0.94), followed by an LGR + LGR classifier (balanced accuracy: 0.84, AUC = 0.94). The results showed that achieved AUC for the LGR + LGR classifier belonged to the 20 biomarkers as follows: TMEM212, SNORD115-13, ATP1A4, FRG2, CFHR4, ZCCHC13, FLJ46361, LY6G6E, ZNF323, KRT28, KRT25, LPPR5, C10orf99, PRKACG, SULT2A1, GRIN2C, EN2, GBA2, CUX2, and SNORA66.ConclusionsThe best performance was achieved using the LGR feature selection procedure and MLP classifier. Results show that the 20 biomarkers had the highest score or ranking in breast cancer detection.

Journal of pediatric nephrology, May 5, 2014

Renal tubular acidosis (RTA) is a rare genetic disorder. It has four clinical types, and type 3 d... more Renal tubular acidosis (RTA) is a rare genetic disorder. It has four clinical types, and type 3 demonstrates a mixed pattern of tubular dysfunction. The causative gene for type 3 RTA (CAII) is located on the 8q22 locus and encodes a protein called carbonic anhydrase II. In this study, we analyzed the entire exons and flanking regions of the CAII gene in a child suffering renal tubular acidosis with an autosomal recessive pattern that was diagnosed with type3 RTA. DNA was extracted from the blood sample of the patient and his parents by the salting out extraction method. The exons and flanking regions of the CAII gene were amplified using polymerase chain reaction (PCR). We performed exon direct sequencing by forward and reverse primers, which were designed by primer3 program. No mutation was found following the screening of the entire coding sequence of the CAII gene. It is likely that another gene might be involved in this case. In other words, other types of RTA have to be considered.

PubMed, May 31, 2023

Objective: The embryo implantation includes a complex sequence of signaling events, comprising nu... more Objective: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. Methods: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. Results: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. Conclusions: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.

Journal of Mazandaran University of Medical Sciences, Aug 10, 2021

Background and purpose: Hyperlipidemia is one of the main risk factors for coronary artery diseas... more Background and purpose: Hyperlipidemia is one of the main risk factors for coronary artery disease and is defined as abnormal elevation of lipids or lipoproteins in the blood. Pcsk9 is the ninth member of the proprotein convertase family that binds to the LDLR on the surface of the hepatocyte, leading to degradation of LDLR in lysosomes which could cause hyperlipidemia. The present study aimed to analyze the methylation status of pcsk9 promoter in patients with hyperlipidemia. Materials and methods: This case-control study was conducted in 50 patients with hyperlipidemia and 50 healthy controls. DNA isolation from whole blood was performed using salting out procedure. Promoter methylation of the Pcsk9 gene was analyzed by methylation-specific PCR (MSP). Ten MSP products were sequenced to confirm the data obtained. Results: According to MSP results, methylation pattern of pcsk9 gene promoter displayed an unmethylated status among the patients and control individuals. In other words, no methylation was seen in case and control samples. Conclusion: The current study showed no significant association between PCSK9 methylation pattern and blood lipid profile level in case group and control group.

Research Square (Research Square), Sep 7, 2022

Background:Spinal muscular atrophy (SMA) is a rare autosomal recessive inherited neuromuscular di... more Background:Spinal muscular atrophy (SMA) is a rare autosomal recessive inherited neuromuscular disease with about 1:6000 to 1:10,000 in newborns. Objectives:To evaluate the copy number variation of SMN1 and SMN2 genes between two generations, we experimented on 221 core families, including 221 patients and their parents (n=442). Materials & methods: Before sample collection, all cases were subjected to clinical diagnosis, electromyography, and nerve conduction velocity test. Moreover, DNA samples were analyzed by multiplex ligation-dependent probe ampli cation. Results: In this study, 92.7% of patients' SMN1 deletions were homozygous, whereas 7.3% of the SMN1 deletions were heterozygous. On the other hand, 92.9% of the parents had one copy of SMN1, and the remaining had two copies of SMN1. Since SMN2 has a disease-modifying role, accurate determination of SMN2 copy number can be helpful in the case of prognosis and genotype-phenotype correlation. The average SMN copies from parents represent the copy number in the parent's generation. Evaluations showed a negative correlation between the copy number of SMN1 and SMN2in children and their parents. Besides, when the average of SMN2 copy numbers was two in the parent's generation, 81% of the children were type I, and the rest were Type II/III. Also, in cases with three or more SMN2copy numbers in parents, approximately 90% of children were either type II or III. Conclusion: Accordingly, there is a possibility that the SMN2 copy numbers in parents could predict the disease severity in the next generation.

Scientific Reports, Mar 22, 2022

We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of pat... more We studied the alpha-globin gene genotypes, hematologic values, and transfusion-dependence of patients with Hb H disease. Molecular characterization of alpha-thalassemia was performed. We identified 120 patients with Hb H disease. Of these patients, 35 (29.16%) had deletional form of Hb H disease, and 85 (70.83%) had different form of non-deletional Hb H disease. The most frequently observed Hb H genotypes were-Med /-α 3.7 in 33 patients (27.5%), α CD19(-G) α /αCD19(-G) α in 25 cases (20.83%), α polyA2 α/α polyA2 α in 15 (12.5%), and α polyA1 α/α polyA1 α in 13 (10.83%) respectively. The probability of receiving at least one transfusion blood in deletional form was observed in 3 of 35 (8.57%) patients which just seen in 3 of 33 (9%) patients with-Med /-α 3.7 genotype. This form was also observed in 8 of 85 (9.4%) patients in non-deletional Hb H diseases which five of them had Med deletion in compound with alpha globin point mutations. Nondeletional Hb H disease was more severe than deletional Hb H disease requiring more blood transfusions. We can recommend that Med deletion in compound with alpha-globin point mutations, polyA1 and constant spring in homozygous form needs to be taken into consideration when offering counseling to high-risk couples. Alpha thalassemia is one of the most common monogenic disorders in the Mediterranean region, Middle East and East and Southeast Asia, as well as in countries with migration from these regions 1,2. The clinical manifestations of alpha globin abnormalities vary from the silent carrier state, in which only one α-globin gene is deleted, to fatal hydrops fetalis, in which all four α-globin genes are missing 3. Hemoglobin H (Hb H) disease is caused by the loss of three α-globin genes, when there is only one functional alpha globin gene the patient produce a form of hemoglobin (Hb) composed of four β-chain (β4) called Hb H 4. The clinical severity of patients with Hb H disease is variable, even in the presence of similar genotype, which is probably due to genetic and environmental modifiers 5. More than 95% of α-thalassemia syndromes are caused by deletional abnormalities while the rest result from point mutations 6. Hb H patients also have been classified as mild, intermediate or severe phenotypes. Mild phenotype included the patients, who diagnosed above 4 years of age, Hb levels above 9.0 g/dl, transfusion-independent, normal growth, minimal bone changes and slight splenomegaly. Intermediate phenotype included patients diagnosed between 2 ± 4 years, Hb more than 8.0 g/dl, transfusion-independent, with mildly impaired growth, some bone abnormalities and moderate splenomegaly. Severe phenotype included patients with severe anemia, Hb less than, 8.0 g/l, needing frequent or occasional transfusions. Hb H Patients with severe phenotype had impaired growth, moderate to severe bone changes and splenomegaly 7. There are two types of Hb H disease, deletional and non-deletional. The first type is the most common form of Hb H disease, is caused by compound heterozygosity with a double α-globin gene deletion on one allele and a single α-globin gene deletion on the other allele (16p13.3). Second type is the non-deletional form of Hb H disease which at least one of the genetic abnormalities was non-deletional 8. Non-deletional Hb H disease is

Jundishapur Scientific Medical Journal, Jan 21, 2018

Majallah-i taḥqīqāt-i ̒ulūm-i pizishkī-i Zāhidān, May 31, 2015

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common gene... more Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders. Genetic studies have demonstrated an important allelic variability among patients but very few data are known about the genetic variation in Iranian populations. Case Presentation: In this study, in order to verify the ADPKD in a patient with some clinical symptoms and study the variations of the PKD1 gene for the first time in Iranian population, the PKD1 gene was entirely sequenced. Coding exons analysis of PKD1 by exon direct sequencing was performed. Molecular genetic testing found a novel mutation in the patient. Conclusions: It was a missense mutation CAT > GAT at position 3311 in exon 30 of PKD1. CAT > GAT causes the conversion of amino acids histidine to argenine and change the transmembrane domain and proper function of the polycystin 1 protein.

PubMed, Sep 1, 2017

Introduction: Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose... more Introduction: Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose per fraction through complex treatment techniques. The increased complexity leads to longer dose delivery times for each fraction. The purpose of this study is to investigate the impact of prolonged fraction delivery time with high-dose hypofractionation on the killing of cultured ACHN cells. Methods and materials: The radiobiological characteristics and repair half-time of human ACHN renal cell carcinoma cell line were studied with clonogenic assays. A total dose of 20 Gy was administered in 1, 2 or 3 fractions over 15, 30 or 45 min to investigate the biological effectiveness of radiation delivery time and hypofractionation. Cell cycle and apoptosis analysis was performed after 3-fraction irradiation over 30 and 45 min. Results: The α/β and repair half-time were 5.2 Gy and 19 min, respectively. The surviving fractions increased with increase in the fraction delivery time and decreased more pronouncedly with increase in the fraction number over a treatment period of 30 to 45 min. With increase in the total radiation time to 30 and 45 min, it was found that with the same total dose, 2- and 3-fraction irradiation led to more cell killing than 1-fraction irradiation. 3-fraction radiation induced G2/M arrest, and the percentage of apoptotic cells decreased when the fraction delivery time increased from 30 min to 45 min. Conclusion: Our findings revealed that sublethal damage repair and redistribution of the cell cycle were predominant factors affecting cell response in the prolonged and hypofractionated irradiation regimes, respectively.

OBM Genetics

Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited... more Familial Mediterranean Fever (FMF) is classified as an autoinflammatory genetic disease inherited by mutations in MEFV. These mutations can affect the dysregulation of inflammatory processes in the human body and lead to fever and pain in the chest and abdomen. Many known missense mutations in MEFV are linked to FMF disease. Mutations in MEFV in most cases are located on the short arm of chromosome 16 and can impair the function of the pyrin protein. In this research, we aimed to examine the entire exons of MEFV for 13 cases (8 females and 5 males) with FMF diagnosis from Southwest Iran. Hence, we amplified and sequenced the exons of MEFV and then, in-silico analysis of detected changes was applied to estimate the probability of pathogenicity for the identified variants. Finally, we found five single nucleotide substitutions, including M694V (c.2080A>G), R202Q (c.605G>A), E447G (c.1430A>G), E148Q (c.442G>C), and V726A (c.2177T>C), in the under-represented patients. Th...

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer ... more Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair...

Supplementary Data from Multiple Repair Pathways Mediate Tolerance to Chemotherapeutic Cross-link... more Supplementary Data from Multiple Repair Pathways Mediate Tolerance to Chemotherapeutic Cross-linking Agents in Vertebrate Cells

Iranian biomedical journal

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common gene... more Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 (16p13.3, 46 exons) and PKD2 (4q21, 15 exons). Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. Methods: In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. Results: Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel...

Cancer Letters, 1994

An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying ... more An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying the possibility of induction of adaptive response to various doses of radiation following treatment with chemotherapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D (ACT-D) at 10 micrograms/kg body weight (therapeutic dose range) were injected intravenously 3 h prior to whole body gamma-irradiation. Irradiation at various doses from 1-4 Gy was carried out at a dose rate of 45 cGy/min. Animals were killed at 24, 36 and 48 h post-irradiation. The results obtained in this study clearly indicate a significant difference for radiation induced micronuclei (MN) in polychromatic erythrocytes (PCEs) with P value < 0.001 over the dose range used. When used in combination with radiation, neither ACT-D nor BLM-S caused a synergistic or additive effect. Irradiated animals showed a higher incidence of micronuclei formation in the presence of ACT-D and BLM-S. However, in both cases, the number of MN induced in PCEs was less than the sum of MN induced by radiation and ACT-D or BLM-S alone. The effect of combined treatment was reduced by a factor of 1.5 for BLM-S and greater than 1.5 for ACT-D treated animals. These observations indicate that although a small amount of ACT-D or BLM-S reaches the bone marrow cells via the circulation, these drugs might produce effects which make bone marrow cells resistant to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal hemopoeitic tissue.

Neurological Sciences, 2021

Parkinson’s disease (PD) is known as one of the most common degenerative disorders related to the... more Parkinson’s disease (PD) is known as one of the most common degenerative disorders related to the damage of the central nervous system (CNS). This brain disorder is also characterized by the formation of Lewy bodies in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta (SNc), which consequently leads to motor and non-motor symptoms. With regard to the growing trend in the number of cases with PD and its effects on individuals, families, and communities, immediate treatments together with diagnostic methods are required. In this respect, long non-coding ribonucleic acids (lncRNAs) represent a large class of ncRNAs with more than 200 nucleotides in length, playing key roles in some important processes including gene expression, cell differentiation, genomic imprinting, apoptosis, and cell cycle. They are highly expressed in the CNS and previous studies have further reported that the expression profile of lncRNAs is disrupted in human diseases such as neurodegenerative disorders. Since the levels of some lncRNAs change over time in the brains of patients with PD, a number of previous studies have examined their potentials as biomarkers for this brain disorder. Therefore, the main purpose of this study was to review the advances in the related literature on lncRNAs as diagnostic, therapeutic, and prognostic biomarkers for PD.

British Journal of Medicine and Medical Research, 2016

Aims: To examine simultaneous effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on w... more Aims: To examine simultaneous effects of Conjugated Linoleic Acid (CLA) and L-carnitine (LC) on weight gain in diet induced obese rats. Study Design: Experimental study. Place and Duration of Study: Department of Nutrition, Faculty of Para-Medical Sciences, Ahvaz Jundishapur University of Medical Sciences (January 2014 to January 2015). Methodology: Forty male Wistar rats were randomly divided into two groups: Normal fat diet Original Research Article Nazari et al.; BJMMR, 12(1): 1-8, 2016; Article no.BJMMR.21609 2 (n=8), and High fat diet (HFD) (n=32). After eight weeks, the second group maintained HFD and was subdivided into 4 categories: Corn Oil group, 500 mg CLA, 200 mg LC, and 500 mg CLA+ 200 mg LC (all doses per kg body weight), which were administered by oral gavage for four weeks. Body weights were measured and recorded weekly by means of a digital scale. SPSS Version 16 was used for statistical analysis. Results: At the end of eighth week, a significant difference in weights was observed between HFD (295.43±5.36 gr) and NFD (246.38±6.48 gr) group. After four weeks, LC significantly reduced weight gain by 7.5% (P = .047). Trend of weight gain in CLA and LC + CLA groups were decelerated (24 and 25 gr respectively), but it was statistically insignificant (P = .08, .12 respectively). Conclusion: Findings of this experimental study showed that a high fat diet led to obesity and combined LC and CLA could decelerate weight gain to some extent. However, it needs further work to validate reliability in human.

Molecular Genetics & Genomic Medicine

Biomedical Research, 2018

Prenatal diagnosis of chromosomal abnormalities is an important challenge for pregnancy managemen... more Prenatal diagnosis of chromosomal abnormalities is an important challenge for pregnancy management has relied on conventional cytogenetic analysis of cultured amniotic fluid, chorionic villi, or fetal blood for a long time. New molecular methods included FISH and QF-PCR on uncultured amniotic fluid or chorionic villi have been applied recently for the rapid aneuploidies detection in chromosomes 13, 18, 21, X and Y. Both molecular methods are quicker than Karyotype as conventional cytogenetic technique. The advantages of QF-PCR include detection of trisomy, mosaicism and maternal cell contamination. This technique is more cost effective, less labor-intensive and more suitable for large sample numbers in comparison to FISH. FISH is a robust method and extensively validated. It detects mosaicism and trisomy. Herein we aimed to assess prenatal diagnosis of aneuploidies in chromosomes 13, 18, 21, X and Y. For this aim, amniotic fluid samples have collected for analysis of common chromosomal aneuploidies using Karyotype, FISH and QF-PCR methods. 69 samples have obtained by amniocentesis from 15 th-18 th week of pregnancies and subjected for comparative analysis by three techniques: FISH, QF, and Karyotype with the same accuracy concerning the detection of trisomy 13, 18, 21, and sex chromosomes X and Y. We conclude that molecular techniques are rapid-reliable methods for analysis of chromosome number in uncultured amniotic fluid. Nevertheless, QF-PCR and FISH are an alternative option, if timing is a limiting factor. This report in line with previous studies emphasizes the importance of molecular techniques for the prenatal identification of the numerical chromosomal abnormalities and ultimately management of pregnancies saving patients from anxiety.