mansour heidari

Hereditary sensory autonomic neuropathy type VIII (HSAN-VIII) is a rare genetic disease that occurs due to mutations in the PRDM12 gene. Here, we describe a novel homozygous mutation c.826_840dupTGCAACCGCCGCTTC (p.Cys276_Phe280dup) on exon 5 in the PRDM12 gene identified by WES and confirmed using Sanger sequencing method.

Acute myeloid leukemia (AML) is a heterogeneous and complex malignancy characterized by rapid cellular proliferation, an aggressive clinical course, and generally high mortality. Transforming growth factor-beta (TGF-β) plays a significant role in tumorigenesis. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β superfamily whose expression is mainly controlled by the Smad signaling pathway. Studies have shown that this protein can control and induce the expression of some microRNAs during the cancer treatment process. MiR-424-5p plays an essential role in various types of cancer at different stages of tumorigenesis, including the promotion and/or inhibition of tumorigenesis, regulation of tumor development in the tumor microenvironment, and influencing cancer chemotherapy outcomes. The aim of this study was to evaluate the induction of cell death in the U937 myeloid leukemia cell line co-cultured with genetically engineered adipose-derived stem cells (ADSCs) expressing a high level of BMP4 through miR-424-5p. The induction of cell death and apoptosis in the U937 cell line was assessed using MTT and Annexin V/ PI assays, respectively. The expression of miR-424 and TGF-β was determined in the co-culture system using real-time PCR. The results of MTT and Annexin V/ PI assays showed that BMP4-expressing adipose-derived stem cells (ADSCs) induced cell death in U937 cells in the co-culture system. Co-culture of engineered ADSCs with the U937 cell line led to the downregulation of miR-424 and TGF-β genes in U937 cells. In the current study, a new strategy based on BMP4 induction was designed to significantly suppress the cell viability of the leukemia cell line U937. It appears that the use of engineered ADSCs could be useful for the treatment of hematological malignancies.

 The numerical and structural abnormalities of chromosomes are the most common cause of infertility. Here, we evaluated the prevalence and types of chromosomal abnormalities in Iranian infertile patients.

 We enrolled 1750 couples of reproductive age with infertility, who referred to infertility clinics in Tehran during 2014- 2019, in order to perform chromosomal analysis. Peripheral blood samples were obtained from all couples and chromosomal abnormalities were evaluated by G-banded metaphase karyotyping. In some cases, the detected abnormalities were confirmed using fluorescence in-situ hybridization (FISH).

 We detected various chromosomal abnormalities in 114/3500 (3.257%) patients with infertility. The prevalence of chromosomal abnormalities was 44/114 (38.596%) among infertile females and 70/114 (61.403%) among infertile males. Structural chromosomal abnormalities were found in 27/1750 infertile females and 35/1750 infertile males. Numerical chromosomal abnormalities were found in 17/1750 of females and 35/1750 of males. The 45, XY, rob (13;14) (p10q10) translocation and Klinefelter syndrome (47, XXY) were the most common structural and numerical chromosomal abnormalities in the Iranian infertile patients, respectively.

 In general, we found a high prevalence of chromosomal abnormalities in Iranian patients with reproductive problems. Our study highlights the importance of cytogenetic studies in infertile patients before starting infertility treatments approaches.

Herein we investigated mutations in the ABCA4 gene in an Iranian patient with Stargardt disease using whole exome sequencing (WES). We evaluated genetic alterations in a 13-year-old Iranian girl with Stargardt disease and her family using WES. The target sequences for the proband and her parents were then amplified through polymerase chain reaction (PCR) and the obtained products were screened for mutations in ABCA4 gene by Sanger chain terminating dideoxy nucleotide sequencing. Two novel potentially pathogenic mutations in compound heterozygous state (c.2713del p.E905Rfs*27 and c.5172G>A p.W1724X) were identified in ABCA4 gene which may contribute to the proband’s Stargardt disease phenotype. In general, the WES successfully identified novel causal mutations in ABCA4 gene which may be used for genetic counseling, prenatal diagnosis (PND), and preimplantation genetic diagnosis (PGD) of Stargardt disease.

Cancer stem cells (CSC), as responsible issues to cancer development and progression, play a crucial role in tumorigenesis, recurrence, metastasis, and chemoresistance. Both hyperthermia and photodynamic therapy (PDT) may be effective for cancer treatment, particularly when combined with other therapeutic approaches. This study aimed to evaluate the effect of hyperthermia combined with PDT on colorectal CSC and the gene expression of the CSC markers, presenting a more effective approach for cancer therapy.

The study was conducted in the Pasteur institute of Iran, Tehran, Iran in 2018. We evaluated the anticancer role of hyperthermia, Gold nanoparticles coated with curcumin (Cur-GNPs) in PDT and combination of the two approaches on cell viability and the expression of CSC markers, Nanog and Oct4 in colorectal cancer cell line HT-29. The cytotoxicity effect of Cur-GNPs against the cells was assessed in vitro. The cell viability was assessed using MTT assay, and the expression analysis of the CSC genes was evaluated using a q-real-time PCR.

Cell viability was decreased by PDT (P=0.015) and the combination therapy (P=0.006) but not by hyperthermia alone (P=0.4), compared to control. Also, the expression of CSC markers, Nanog and Oct4 was shown to significantly down-regulate in all hyperthermia, PDT and combination groups.

Hyperthermia combined with PDT was indicated to be more efficient in eliminating tumors than hyperthermia or PDT alone.

Transforming growth factor-beta (TGF-β) plays a significant role in tumorigenesis. MiR-181b is a multifunctional miRNA involved in numerous cellular processes, such as cell fate and cell invasion. This study aimed to examine whether the co-culture of adipose-derived stem cells (ADSCs), highly expressing bone morphogenetic protein-4, with the U937 cell line, which is a human myeloid leukemia cell line, is able to induce cell death in this cancer cell line, considering the potential ability of ADSCs to migrate from tumor sites. Cell surface markers, namely CD73 and CD105, were analyzed to verify the identity of mesenchymal stem cells isolated from adipose tissue. Besides, the osteogenic and adipogenic differentiation potentials of ADSCs were evaluated. The induction of cell death and apoptosis in the U937 cell line was assessed using MTT and annexin V/ PI assays, respectively. The expression levels of miR-181 and TGF-b were determined in the co-culture system using real-time PCR. The results of MTT and annexin V/ PI assays showed that BMP4-expressing ADSCs could inhibit cell viability and induce apoptosis in U937 cells in the co-culture system. The co-culture of ADSCs, highly expressing BMP-4, with the U937 cell line led to the downregulation of miR-181 and TGF-β genes in the human cancer cell line. ADSCs may further be studied as a candidate for the treatment of hematological cancers.

Homeodomain transcriptional regulatory proteins, which are encoded by Homeobox (HOX) genes, play critical roles in both normal development and carcinogenesis. Previous studies have shown that the expression of HOX genes is deregulated in numerous tumors and this expression is specific to each cancer based on the arising embryonic origin tissue and the site of tumor.

In this in vitro study, the expression levels of HOXA10, CDX1, CDX2, TGIFLX, TGIFLY, and OCT1 genes were compared across 10 different human colorectal cancer cell lines with different differentiation stages. Subsequently, the effect of TGIFLX siRNA-mediated knockdown on the expression levels of CDX1, CDX2, and OCT1 genes was analyzed in SW948 cell line.

The obtained results revealed that these homeobox genes were differentially expressed in different colorectal cancer cell lines. Furthermore, the siRNA-mediated knockdown of TGIFLX led to higher levels of CDX1, CDX2, and OCT1 expression.

Our data suggested that TGIFLX plays an important role in the upstream regulation of CDX1, CDX2, and OCT1 genes.

Atorvastatin exerts neuroprotective effects on the treatment of central nervous system disorders. Morphine analgesic tolerance and dependence remain as major concerns in medicine. Nitric oxide (NO) pathway mediates the development of opioid analgesic tolerance and dependence, as well as atorvastatin neuroprotection.

The present study aimed to assess the possible involvement of the NO/cGMP pathway in the process of the effects of atorvastatin on morphine physical dependence.

Dependence was induced by repetitive injection of morphine sulfate. Naloxone was injected at the dose of 4 mg/kg on the last day of the experiment to assess withdrawal signs. Animals received atorvastatin (1, 5, 10, and 20 mg/kg, orally). Nitric oxide synthase (NOS) inhibitors and ODQ were injected before protective dose of atorvastatin. The gene expression of NOS isoforms was evaluated by real-time PCR. Thereafter, the hippocampal levels of cGMP and nitrite were measured.

Treatment with atorvastatin 10 mg/kg significantly attenuated naloxone-induced withdrawal behaviours. The administration of L-NAME, aminoguanidine, and ODQ before atorvastatin enhanced its effects. The treatment with atorvastatin significantly decreased the nitrite and cGMP levels as well as NOS gene expression in the hippocampus of dependent animals.

It can be concluded that atorvastatin, possibly, through inducible NOS, could alleviate morphine dependence and withdrawal signs.

The spondylo-meta-epiphyseal dysplasia (SMED) short limbs-hand type is a rare autosomal recessive disease, which is characterized by premature calcification leading to severe disproportionate short stature and various skeletal changes. Defective function of a conserved region encoding discoidin domain receptor tyrosine kinase 2 (DDR2 protein) by the discoidin domain-containing receptor 2 (DDR2 gene) is cause of this disease. The purpose of present study was to investigate disease-causing mutations on DDR2 gene in an Iranian family with SMED, and predict the DDR2 protein molecular mechanism in development of SMED.

In the present study, we evaluated a 2-year-old male with SMED. Detection of genetic changes in the studied patient was performed using Whole-Exome Sequencing (WES). PCR direct sequencing was performed for analysis of co-segregation of variants with the disease in family. Finally, in silico study was performed for further identification of molecular function of the identified genetic variant.

We detected a novel splice-site mutation (NM_001014796: exon9: c.855+1G>A; NM_006182: exon8: c.855+1G>A) in DDR2 gene of the studied patient using WES. This mutation was exclusively detected in patients with homozygous SMED, not in healthy people. The effects of detected mutation on functions of DDR2 protein was predicted using in silico study.

The causative mutation in studied patient with SMED was identified using Next-generation sequencing (NGS), successfully. The identified novel mutation in DDR2 gene can be useful in prenatal diagnosis (PND) of SMED, preimplantation genetic diagnosis (PGD), and genetic counseling.

The spondylo-meta-epiphyseal dysplasia (SMED) short limbs-hand type is a rare autosomal recessive disease, which is characterized by premature calcification leading to severe disproportionate short stature and various skeletal changes. Defective function of a conserved region encoding discoidin domain receptor tyrosine kinase 2 (DDR2 protein) by the discoidin domain-containing receptor 2 (DDR2 gene) is cause of this disease. The purpose of present study was to investigate disease-causing mutations on DDR2 gene in an Iranian family with SMED, and predict the DDR2 protein molecular mechanism in development of SMED.

In the present study, we evaluated a 2-year-old male with SMED. Detection of genetic changes in the studied patient was performed using Whole-Exome Sequencing (WES). PCR direct sequencing was performed for analysis of co-segregation of variants with the disease in family. Finally, in silico study was performed for further identification of molecular function of the identified genetic variant.

We detected a novel splice-site mutation (NM_001014796: exon9: c.855+1G>A; NM_006182: exon8: c.855+1G>A) in DDR2 gene of the studied patient using WES. This mutation was exclusively detected in patients with homozygous SMED, not in healthy people. The effects of detected mutation on functions of DDR2 protein was predicted using in silico study.

The causative mutation in studied patient with SMED was identified using Next-generation sequencing (NGS), successfully. The identified novel mutation in DDR2 gene can be useful in prenatal diagnosis (PND) of SMED, preimplantation genetic diagnosis (PGD), and genetic counseling.

The Syntaxin Binding Protein 1 (STXBP1) plays an important role in the regulating neurotransmitter release and synaptic vesicle fusion through binding to syntaxin-1A (STX1A) and changing its conformation. In this study, we identified a de novo mutation (c.C1162T: p. R388X) in exon 14 of STXBP1 gene causing an epileptic encephalopathy, early infantile, non-epileptic movement, and unclassified infantile spasms disorders in a 5-years-old boy by whole exome sequencing.  The segregation of this genetic variant was examined in the patient as well as in his parents. We found the R388X in heterozygous state in the proband but not in his parents. This genetic change could be due to De nova mutation or germline mosaicism.

Cirrhotic cardiomyopathy is a complication of uncured cirrhosis which is associated with hyporesponsiveness of the heart to sympathetic stimulation. The enhancement of portal pressure, nitric oxide (NO) level, pro-inflammatory mediators and down-regulation of Suppressor of Cytokine Signaling 1 (SOCS1) are involved in this situations. The present study seeks to examine the beneficial effect of thalidomide on cirrhotic cardiomyopathy.

The male rats were grouped as: Sham/saline, Sham/Thalidomide, Bile Duct Ligation (BDL)/saline and BDL/Thalidomide. BDL model of cirrhosis was used. In the treatment groups, thalidomide (200 mg/kg/day) was administrated by intragastrial gavage for 28 consecutive days, the chronotropic response was assessed in isolated atria by isoproterenol stimulation. Serum levels of NO, IL-6 and TNF-α hepatic level were evaluated. The intrasplenic pulp pressure (ISPP) as the portal pressure and histopathologic assessment were assessed. Real time RT-PCR was used for the evaluation of SOCS1 gene expression.

Our results showed that thalidomide administration could significantly increase the atrial chronotropic response in BDL animals. The increased level of portal pressure decreased by thalidomide in BDL animals. Thalidomide could ameliorate the histopathological conditions of BDL rats. Furthermore, the chronic treatment by this drug diminished the elevated levels of NO, TNF-α and IL-6 in BDL animals. On the other hand, hepatic SOCS1 expression was up-regulated by thalidomide treatment in this group.

Thalidomide improves the chronotropic hyporesponsiveness of isolated atria in BDL. This effect is probably mediated by the inhibiting NO, TNF-α and IL-6 production, reducing portal pressure and increasing the expression of SOCS1.

Breast cancer is one of the most prevalent malignancies among women. Patients whose suffering from this condition, as a result of the use of conventional therapies often have a poor response to treatment and the relapse among them is frequent. In this study, the effects of staphylococcal enterotoxin type B on BAK، FAS، BAX، TNF-a، BCL-2 و Survivin genes expression in human breast adenocarcinoma cells (MCF-7) was examined. Staphylococcal enterotoxin B is a powerful member of the Staphylococcus aureus toxins family, which is known as an anticancer agent with potential for killing cancer cells.

The experimental study was carried out at the Biotechnology Research Center of Islamic Azad University, Shahrekord Branch. By using Lipofectamine 2000 reagent, MCF-7 cells transfected with the pcDNA3.1(+)-seb (recombinant) and pcDNA3.1(+) (non-recombinant) plasmids and were selected by culturing in a selective medium of RPMI- 1640 containing 600 μg / mL antibiotic G418. Then, the expression of BAK, FAS, BAX, TNF-a, BCL-2, and Survivin genes in transfected cells were analyzed by real time PCR. Student's t-test, SPSS Inc., Chicago, IL; Version 16 and also Excel program for statistical analysis were used.

The results of this study indicated that staphylococcal enterotoxin type B (SEB) remarkably changes the expression of apoptotic related genes in MCF-7 cell line. It was observed a significant increase in the expression of BAK, FAS, BAX, and TNF-a genes, the expression of BCL-2 and Survivin genes significantly decreased compared to the control group (P=0/032).

Staphylococcal enterotoxin type B has an inhibitory effect on the growth, proliferation and invasion of breast adenocarcinoma cells through altering the expression of the genes involved in the apoptosis process. Therefore, it seems that there is a good research field for the use of this toxin in the control and treatment of human breast adenocarcinoma.

The OCT1 and TGIFLX transcription factors are members of homeodomains whose expressions have been implicated in normal and abnormal development. However, the expression of TGIFLX and OCT1 in colorectal cancer is unknown. This study aimed to detect the expression of OCT1 and TGIFLX in clinical samples of colorectal cancer. Twenty-six pairs of colorectal cancer tissue and adjacent non-tumoral tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of TGIFLX and OCT1 was detected by real time reverse transcriptase polymerase chain reaction (RT-PCR). OCT1 was down-regulated in colorectal carcinoma samples in both males (58.33%) and females (57.14%). By contrast, TGIFLX was mainly (41.63%) expressed in colorectal tumors of males' samples but not in para-neoplastic normal tissues. OCT1 expression was not significantly associated with the gender and site of primary tumor (P>0.05), but the expression of TGIFLX was associated with male patients (P<0.05). In conclusion, dysregulation of OCT1 and TGIFLX genes might be novel prognostic biomarkers for patients with colorectal cancer.

The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MiRNAs are a group of non-coding RNAs that regulate posttranscriptional expression of target genes. Dysregulation of miRNAs has been reported in associated with a variety of malignancies, including colorectal cancers. This study aimed to analyze the differential expression of miRNAs in plasma samples of colorectal cancer (CRC) patients to examine their potential value as diagnostic biomarkers. In this case- control study, 74 plasma samples of CRC patients with stage II-IV and 36 healthy controls were collected. miR-18a, miR-34a, miR-181b and miR-146b were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase PCR (qRT-PCR). Then, statistical analyzes were performed to determine the relationship between miRNAs expression and clinical-pathological characteristics. The significantly elevated levels of miR-18a and miR-34a were detected in plasma samples compared to the healthy groups (P<0.001). ROC showed an area under the ROC curve (AUC) of 0.85 and P<0.001 for miR-18a, 0.74 and P<0.001 for miR-34a. There were no significant dysregulation of miR-146b and miR-181b between patients and controls (P>0.05). Our results indicated that the expression levels of miR-18a and miR-34a are systematically elevated in CRC plasma samples. It might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and served as tumor-associated biomarkers for diagnosis.

One of the most important sources of soft power in the Islamic Republic of Iran is culture and cultural values that can enhance the soft power of Iranian society at the domestic and foreign levels. One point to be taken into account is that Iran has many sources of soft power and should simply redefine soft power by identifying and planning strategic ones. One of the foundations for identifying the sources of soft power in the Islamic Republic is the Constitution, which illustrates all national and religious capacities existing in the field of national power resources. For this purpose, by analyzing the contents of the Constitution, Iran's capacity and potential in the field of power can be recreated and operationalized. In this regard, the present article tries to answer this key question; what are the cultural sources of the soft power of the Islamic Republic of Iran in the Constitution and what are the components of it? The findings of the paper show that the cultural sources of Iran's soft power within the Constitution exist in four areas of national symbols, religious symbols, political values, and knowledge. This shows that Islamic ideology, independence, culture, freedom, justice, science and technology are cited most frequently in the Constitution and have an effective relationship with the software power of Iran.

Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related death worldwide. The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MicroRNAs (miRNAs) have provided new insight into CRC development and have been suggested as reliable and stable biomarkers for diagnosis and prognosis. The aim of this study was to analyze the differential expression of miRNAs at different stages of CRC searching for possible correlation with clinicopathological features to examine their potential value as diagnostic biomarkers.
In this case-control study, plasma and matched tissue samples were collected from 74 CRC patients at stage II-IV as well as blood samples from 32 healthy controls. After exhaustive study of the current literature, eight miRNAs including miR-200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U, Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was applied, where needed.
Significantly elevated levels of miR-21, miR-31, miR-20a, miR-135b, and decreased levels of miR- 200c, miR-145 and let-7 g were detected in both plasma and matched tissue samples compared to the healthy group (P0.05). ROC for tissue miRNAs showed an area under the ROC curve (AUC) of 0.98 and P Our results indicate that the expression levels of microRNAs are systematically altered in CRC tissue and plasma. In conclusion, detection of miR-21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as tumor-associated biomarkers for diagnosis.

Non-syndromic aniridia (iris hypoplasia) as an autosomal dominant eye disorder results from the chromosomal abnormalities and mutations within the paired box gene 6 (PAX6). The aim of this study was to investigate on the clinical and the underlying genetic alteration in PAX6 gene in a large pedigree with five generations of Iranian family with an autosomal dominant aniridia. Here, we reported unique clinical features in terms of presenting nystagmus, ptosis, minimal iris abnormality, foveal hypoplasia and late-onset clinical limbal stem cell deficiency. Genomic DNA was extracted from the affected members and polymerase chain reaction (PCR) was conducted using specific primers to amplify coding sequence of PAX6. Then, PCR products were subjected to bidirectional dye terminator sequencing. A heterozygous transversion mutation A→T (c.1268A>T, p.*423Lext*15) in exon 13 of PAX6 was identified in all affected individuals, but not in the healthy members. This is the first report of non-stop mutation in PAX6 gene in an Iranian family accompanied with an isolated form of unusual congenital aniridia running within this family.

Recurrent Aphthous Stomatitis (RAS) is one of the most common diseases of the oral cavity all over the world (5-66%). RAS has a multifactorial etiology, while psychological factors such as stress and anger play a role in its manifestation. The serotonergic mechanisms particularly the serotonin-transporter gene (5-HTT) may affect the risk of psychological alterations and stress response. The aim of the present study was to evaluate the polymorphism of the promoter region of 5-HTT (5-HTTLPR) in the patients with RAS, compared to that in the control subjects.
In this case-control study, 100 patients with RAS and 100 healthy subjects were enrolled. PCR was performed on DNA of the samples, using a pair of primers capable of distinguishing S/L alleles and replicating 5-HTTLPR.
No statistically significant difference existed between LL and LS genotype frequencies in the case and control groups. However, SS genotype frequency was significantly higher in the case group, as compared to the control group (p=0.001).
The conclusion of the present study demonstrated that S allele could approximately double the risk of RAS.

Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin 50 gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC).
Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist’s examination, and the pedigree analysis was performed. PCR amplifications were performed corresponding to coding region and intron-exon boundaries of GJA8, a candidate gene responsible for ADCC. PCR products were subjected to bidirectional sequencing, and the co-segregation of identified mutations was examined and finally, the impact of identified mutations on biological functions of GJA8 was predicted by in silico examination.
Three different genetic alterations, including c.130G>A (p.V44M), c.301G>T (p.R101L) and c.134G>T (p.W45L) in GJA8 gene were detected among three probands. Two identified mutations, W45L and V44M have been already reported, while the R101L is a novel mutation and its co-segregation was examined. This mutation was exclusively detected in the ADCC and could not be found among the healthy control group. The result of bioinformatic studies of R101L mutation predicted that this amino acid substitution within GJA8 could be a disease-afflicting mutation due to its potential effect on the protein structure and biological function.
Our results suggest that mutations of lens connexin genes such as GJA8 gene could be one of the major mechanisms of cataract development, at least in a significant proportion of Iranian patients with ADCC.

Autosomal dominant congenital cataract (ADCC) is the most common form of inherited cataracts and accounts for one-third of congenital cataracts. Heterozygous null mutations in the crystallin genes are the major cause of the ADCC. This study aims to detect the mutational spectrum of four crystallin genes, CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD in an Iranian family. Genomic DNA was isolated from whole blood cells from theproband and other family members. The coding regions and flanking intronicsequences of crystalline genes were analyzed by Sanger sequencing in aproband with ADCC. The identified mutation was further evaluated in available family members. To predict the potential protein partners of CRYBA1/A3, we also used an in-silico analysis. A de novo heterozygous deletion (c.272-274delGAG, p.G91del) in exon 4 of CRYBA1/A3 gene, leading to a deletion of Glycine at codon 91 was found. This genetic variation did not change the reading frame of CRYBA1 protein. In conclusion, we identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling.

Acquired azole resistance in opportunistic fungi causes severe clinical problems in immunosuppressed individuals. This study investigated the molecular mechanisms of azole resistance in clinical isolates of Candida glabrata. Six unmatched strains were obtained from an epidemiological survey of candidiasis in immunocompromised hosts that included azole and amphotericin B susceptible and azole resistant clinical isolates. Candida glabrata CBS 138 was used as reference strain. Antifungal susceptibility testing of clinical isolates was evaluated using Clinical and Laboratory Standards Institute (CLSI) methods. Complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) technology, semi-quantitative RT-PCR, and sequencing were employed for identification of potential genes involved in azole resistance. Candida glabrata Candida drug resistance 1 (CgCDR1) and Candida glabrata Candida drug resistance 2 (CgCDR2) genes, which encode for multidrug transporters, were found to be upregulated in azole-resistant isolates (≥2-fold). Fatty acid activator 1 (FAA1) gene, belonging to Acyl-CoA synthetases, showed expression in resistant isolates ≥2-fold that of the susceptible isolates and the reference strain. This study revealed overexpression of the CgCDR1, CgCDR2, and FAA1 genes affecting biological pathways, small hydrophobic compounds transport, and lipid metabolism in the resistant clinical C.glabrata isolates.

Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2′-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P

A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development.

Pemphigus vulgaris (PV) is a relatively rare autoimmune disease characterized by blistering of the skin and mucosa. The main objective of this study was to investigate the possible association between the 5-HTTLPR polymorphism and PV in Iranian patients. For this, 112 PV and 100 controls were enrolled in this study.
In this case-control study, Genomic DNA was extracted from whole blood and genotyping of all participants for the 5-HTTLPR polymorphism was carried out using the polymerase chain reaction (PCR) technique. The genotypes were grouped into three classes: homozygous for the short allele (SS), heterozygous for the short and long allele (LS) and homozygous for the long allele (LL).
Our results showed no significant association between the 5-HTTLPR polymorphism genotypes, LL, SS and LS in PV patients compared to controls. Also, our finding did not reveal any evidence of an association between this disease and the allele frequency of S and L. Taken together, our findings suggested that the 5-HTTLPR polymorphism is unlikely to be a factor contributing to the risk of developing pemphigus vulgaris.
It can be concluded that although 5-HTTLPR polymorphism seems to be associated with some of auto-immune and stress-related disease.