Interleukin 1 alpha (IL1A) polymorphisms and risk of endometriosis in Iranian population: a case-control study.

Endometriosis is one of the most common gynecological diseases and a major cause of pain and infertility. It is influenced by genetic, epigenetic, and environmental factors. Recently, genome-wide association studies have revealed a strong association between IL1A single nucleotide polymorphisms (SNPs) and increased risk of endometriosis in Japanese women. The aim of the present study was to evaluate the association of three IL1A SNPs, rs17561, rs1304037, and rs2856836 with the risk of endometriosis in Iranian population. Totally, 105 women with diagnosis of endometriosis and 102 healthy women as control group were included. Three SNPs of the IL1A, rs17561 G/T, rs1304037 A/G, and rs2856836 T/C, were genotyped by PCR and RFLP. The rs2856836 TC genotype was significantly higher (p = .002; OR = 3.1, 95% CI: 1.5-6.5) in the patients (28.1%) than the control group (12.7%). The rs2856836 CC genotype was significantly higher (p = .047; OR = 2.3, 95% CI: 1.0-5.3) in the patients (17.5%) than the control group (10.8%). The rs2856836 C allele was significantly higher (p = .001; OR = 2.2, 95% CI: 1.4-3.6) in the patients (31.6%) than the control group (17.2%). The IL1A rs2856836 T/C SNP was associated with susceptibility to endometriosis and the rs2856836 C allele may increase the risk of endometriosis in Iranian women.

Discovery of candidate genes for nonsyndromic cleft lip palate through genome-wide linkage analysis of large extended families in the Malay population.

BACKGROUND: Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population. RESULTS: A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1. CONCLUSIONS: We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.

Downregulation of CRNN gene and genomic instability at 1q21.3 in oral squamous cell carcinoma.

OBJECTIVES: This study includes the direct sequencing of cornulin (CRNN) gene to elucidate the possible mechanism of CRNN downregulation and explore the genetic imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples. MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples. RESULTS: No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044). CONCLUSION: This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC. CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.

Overexpression of MMP13 is associated with clinical outcomes and poor prognosis in oral squamous cell carcinoma.

Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.

Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.

The molecular mechanism responsible for sperm DNA fragmentation is not fully understood. Therefore, identifying genes related to the response to DNA damage is an important area of research. Recently, the role of long non-coding RNAs (LncRNAs), especially DNA damage-sensitive RNA1 (DDSR1) in male infertility has been highlighted. In this research, a protein-protein interaction network (PPIN) was constructed using the STRING database, and functional classification was conducted using webgestalt servers. Subsequently, a group of 40 males with a high degree of sperm DNA fragmentation (DFI ≥ 25%) was compared to a control group of 20 healthy males with a normal sperm DNA fragmentation rate (DFI < 25%). To assess gene expression, real-time polymerase chain reaction (PCR) analysis was performed on DNA samples obtained from both healthy and infertile males. Our findings revealed that infertile men with an abnormal DFI index showed significantly lower expression levels of the long noncoding RNA DDSR1, as well as the genes BRCA1, MRE11A, RAD51, and NBN, compared to the control group. Pathway analysis of the network proteins using Reactome indicated involvement in crucial cellular processes such as the cell cycle, DNA repair, meiosis, reproduction, and extension of telomeres. In conclusion, the downregulation of LncRNA and genes associated with the DNA damage response in males with an abnormal DFI suggests that these factors may contribute to the development of sperm DNA fragmentation and could potentially serve as diagnostic markers for further investigation in therapeutic interventions in the future.

Evaluation of Immunohistochemical Expression of Survivin and its Correlation with qRT-PCR Results as a Useful Diagnostic Marker in Gastric Cancer.

Background: Today, survivin is known as one of the most specific cancer proteins; provide unique and practical study opportunities. Clinical value of survivin in gastric cancer (GC) is not yet appointed. To establish the expression level of survivin and its diagnosis value in Iranian patients with GC, we evaluated the association of survivin expression with clinicopathologic factors. Methods: Overall, 60 matched-normal controls with 60 GC samples including 30 cases with evidence of metastasis at time of our study and 30 cases without evidence of metastasis were recruited, in Tehran, Iran during 2008 to 2018. Survivin expression was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) study. Results: Increased expression of survivin at mRNA and protein levels was found in 86.7% and 71.6% of cases, respectively. Evidence indicated a significant difference in survivin mRNA expression level between tumor and nontumoral (marginal) tissues (P<0.001). The difference in expression of survivin mRNA was not significant between metastatic and non-metastatic tumor tissues (P=0.171). Positive immunoreactivity of survivin was observed to be predominantly in the nucleus of tumor cells. A significant difference in survivin protein expression was detected between tumor and non-tumoral tissues (P<0.001) and between metastatic and non-metastatic tumor tissues (P<0.001). There was no significant association between survivin mRNA expression and clinicopathological variables. However, survivin protein expression was significantly correlated with perineural involvement (P<0.018). Conclusion: This data could be supportive of using survivin as a useful diagnostic marker in GC. Although, more research is needed in this area.

Association Between the G82S Polymorphism of the Receptor Gene for Advanced Glycation End-products and Soluble Serum Levels RAGE with Diabetic Nephropathy in the White (Asian) Race.

INTRODUCTION: Diabetic nephropathy is one of the most common severe symptoms of diabetes mellitus. Hyperglycemia can lead to tissue damage and inflammation due to mediators such as receptor for advanced glycation end-products (RAGE). Therefore, in this study, we aimed to investigate the association between the G82S polymorphism of the RAGE gene and diabetic nephropathy in diabetic patients. METHODS: In this case-control study, 356 participants (158 men and 198 women) of Asian race, aged 45 to 65 years, who were diagnosed with type 2 diabetes mellitus based on their fasting plasma glucose levels were enrolled. DNA was isolated from the participants' blood samples and genotyped using TETRA -Primer ARMS-PCR. Serum protein concentration of soluble RAGE (sRAGE) was also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Although we found differences in genotyping of participants between homozygous AA and GG and heterozygous GA in the studied groups, the differences were not significant (P = .568). In addition, we found no significant correlation between the G82S polymorphism of RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared with diabetic patients (P > .05). CONCLUSION: The results of this study indicate no significant association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared to diabetic patients without nephropathy. Therefore, the study suggests that there is probably no association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. DOI: 10.52547/ijkd.7872.

Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure. Up to 50% of all DCM cases have a genetic background, with variants in over 250 genes reported in association with DCM. Whole-exome sequencing (WES) is a powerful tool to identify variants underlying genetic cardiomyopathies. Via WES, we sought to identify DCM causes in a family with 2 affected patients. METHODS: WES was performed on the affected members of an Iranian family to identify the genetic etiology of DCM. The candidate variant was segregated via polymerase chain reaction and Sanger sequencing. Computational modeling and protein-protein docking were performed to survey the impact of the variant on the structure and function of the protein. RESULTS: A novel single-nucleotide substitution (G > A) in exon 9 of MED12, c.1249G > A: p.Val417Ile, NM_005120.3, was identified. The c.1249G > A variant was validated in the family. Bioinformatic analysis and computational modeling confirmed that c.1249G > A was the pathogenic variant responsible for the DCM phenotype. CONCLUSION: We detected a novel DCM-causing variant in MED12 using WES. The variant in MED12 may decrease binding to cyclin-dependent kinase 8 (CDK8), affect its activation, and cause alterations in calcium-handling gene expression in the heart, leading to DCM.

Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients.

OBJECTIVE: Neoadjuvant chemotherapy with 5-fluorouracil (5FU) is one of the most effective treatment options for gastric cancer patients.  However, treatment response varies significantly between patients based on their genetic profile. The purpose of this study was to determine the association between thymidylate synthase (TS) and enolase superfamily member 1 (ENOSF1) polymorphisms, treatment response, and overall survival in patients with gastric cancer. METHODS: The TS and ENOSF1 variants were analyzed in formalin-fixed paraffin-embedded (FFPE) tissue from 100 gastric cancer patients receiving neoadjuvant 5FU-based chemotherapy. Polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) were used to determine TS polymorphisms' genotypes, and the Tetra Arms PCR method was used to identify ENOSF1 polymorphisms. Patients were followed for up to five years, and the association between variants, treatment response, and overall survival (OS) was examined. RESULTS: There was a significant association between the TS 5' UTR polymorphism and response to treatment in patients with gastric cancer who received neoadjuvant 5FU therapy (P=0.032). Patients with the 2R3R genotype responded better to treatment, whereas those with the 3R3R genotype did not respond to treatment. Patients with the 2R2R and 3R3R genotypes had the longest and shortest median survival times, respectively, and the observed differences were significant (p=0.003). There was a statistically significant relationship between rs2612091 and chemotherapy response (P=0.017). Patients with genotype AG did not respond to treatment. CONCLUSION: This study established that the TS 5' UTR and ENOSF1 rs2612091 polymorphisms could be used to predict treatment response and overall survival in patients with gastric cancer who received neoadjuvant chemotherapy based on 5FU.

High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer.

Background: Microsatellite instability (MSI) is considered a key factor in carcinogenesis and a genetic alteration pattern in many types of cancers such as gastric cancer (GC). Although the role of MSI in colorectal cancer (CRC) is well known, its prognostic impact on GC has not been clearly defined. The assessment of MSI in GC has not been documented in the Iranian population yet. Therefore, this study analyzed the association of MSI status with GC in Iranian patients. Materials and Methods: We compared the frequency of MSI at 5 loci from formalin-fixed paraffin-embedded (FFPE) gastrectomy specimens, between metastatic and non-metastatic cases of GC (N = 60). A panel of five quasi-monomorphic markers and a single dinucleotide marker with linker-based fluorescent primers was used. Results: MSI was observed in 46.6% of cases, including MSI-high (H) (33.3%) and MSI-Low (L) (13.3%). Moreover, the most unstable and stable markers in our study were NR-21 and BAT-26 accordingly. MSI-H and MSI were seen more frequently in non-metastatic tumors (p= 0.028 and p= 0.019, respectively). Conclusion: The current study showed MSI status more frequently in non-metastatic GC which may reflect a good prognostic factor in GC like CRC. Although, larger and more comprehensive studies are needed to confirm this statement. A panel consisting of NR-21, BAT-25, and NR-27 mononucleotide markers appears to be reliable and useful markers for detecting MSI in GC in Iranian patients.

HOTAIR Induces the Downregulation of miR-200 Family Members in Gastric Cancer Cell Lines

Background: Gastric cancer (GC) is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. Long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) has recently emerged as a promoter of metastasis in various cancer types, including GC, through the epithelial­mesenchymal transition (EMT) process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process. Methods: AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs. Results: Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05). Conclusion: Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment.

A novel likely pathogenic variant in the FBXO32 gene associated with dilated cardiomyopathy according to whole­exome sequencing.

BACKGROUND: Familial dilated cardiomyopathy (DCM) is a genetic heart disorder characterized by progressive heart failure and sudden cardiac death. Over 250 genes have been reported in association with DCM; nonetheless, the genetic cause of most DCM patients has been unknown. The goal of the present study was to determine the genetic etiology of familial DCM in an Iranian family. METHODS: Whole-exome sequencing was performed to identify the underlying variants in an Iranian consanguineous family with DCM. The presence of the candidate variant was confirmed and screened in available relatives by PCR and Sanger sequencing. The pathogenic effect of the candidate variant was assessed by bioinformatics analysis, homology modeling, and docking. RESULTS: One novel likely pathogenic deletion, c.884_886del: p.Lys295del, in F-box only protein 32 (muscle-specific ubiquitin-E3 ligase protein; FBXO32) was identified. Based on bioinformatics and modeling analysis, c.884_886del was the most probable cause of DCM in the studied family. CONCLUSIONS: Our findings indicate that variants in FBXO32 play a role in recessive DCM. Variants in FBXO32 may disturb the degradation of target proteins in the ubiquitin-proteasome system and lead to severe DCM. We suggest considering this gene variants in patients with recessively inherited DCM.

Augmented Expression of NOGO-A and Its Receptors in Human Retinal Pigment Epithelial Cells Following Treatment with Human Amniotic Fluid.

Background: Nogo-A, a myelin-associated inhibitor for neurite outgrowth, has important role in visual system development. Trans-differentiation ability of human amniotic fluid (HAF) on human retinal pigment epithelial cells (hRPEs) towards neural progenitor cells has been observed in several studies. We aimed to investigate the expression of NOGO-A gene and its receptors as a marker of neural differentiation in HAF-treated hRPE cells. Methods: hRPE cells were cultivated and immune characterized via RPE65 and cytokeratin 8/18 protein markers. Also, the cytotoxicity effect of 30% HAF on hRPE cells was evaluated using ELISA cell death assay. Finally, expression of NOGO-A and its receptors, RTN4R and LINGO1 was evaluated in the cells treated with HAF in comparison with FBS-treated cells using quantitative real-time PCR. Results: Harvested cells showed immunoreactivity for cytokeratin 8/18 and RPE65, confirming the hRPE cell identity. Besides, HAF had no cytotoxic effect on hRPE cells compared with FBS-treated cells. Results showed that NOGO-A and its receptors were expressed in cultured hRPE cells. Besides, comparative gene expression analysis revealed significant increased expression of the investigated genes in HAF-treated hRPE cells compared to FBS-treated cells. Conclusion: Augmented expression of NOGO-A and its receptors can support neural differentiation of hRPE when the cells are treated with HAF. Our outcomes provide more evidences on the trans-differentiation ability of HAF on hRPE cells into neural progenitors and retinal neural cells, but further studies are needed to elucidate the exact mechanism.

Genetic screening of TGFBI in Iranian patients with TGFBI-associated corneal dystrophies and a meta-analysis of global variation frequencies.

PURPOSE: Transforming growth factor beta-induced (TGFBI)-associated corneal dystrophies (CDs) are a clinically heterogeneous group of CDs caused by mutations in the TGFBI gene. Nucleotide sequences encoding two arginine residues at positions 124 and 555 in TGFBI protein are mutation hotspots. We screened regions of TGFBI that include the hotspots in a cohort of Iranian patients with TGFBI-associated CDs. We also performed a meta-analysis for frequencies of all reported TGFBI mutations. METHODS: Twenty-four TGFBI-associated CD-diagnosed patients were recruited. Exons 4 and 12 of TGFBI were amplified by the polymerase chain reaction and sequenced by Sanger protocol. A meta-analysis on reported TGFBI sequence data was done by reviewing all published relevant articles available in NCBI. RESULTS: Twenty-two out of 24 patients had mutations in exons 4 or 12 of TGFBI. The most frequent mutations were p.Arg124Cys, p.Arg124His, and p.Arg555Trp; each of these was found in six families. Three other missense mutations including p.Arg555Gln, p.Ile522Asn, and p.Ala546Thr were also identified. The data suggested a fairly tight genotype/phenotype correlation for the most common CDs. Literature review evidenced that the reported mutations affected less than 30% of the amino acids of the TGFBI protein and that p.Arg124His, p.Arg124Cys, p.Arg555Trp, p.Arg124Leu, p.Arg555Gln, and p.His626Arg were the most frequent mutations. CONCLUSION: TGFBI mutation profile of Iranian patients is very similar to that of the rest of the world. The meta-analysis confirmed the worldwide prevalence of p.Arg124 and p.Arg555, showed that p.His626Arg is also relatively frequent, and evidenced the value of screening exons 4 and 12 of TGFBI.

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population.

Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P=0.001, odds ratio=2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition.

Contribution of variants in and near the IRF6 gene to the risk of nonsyndromic cleft lip with or without cleft palate in a Malay population.

Several studies have shown evidence for the contribution of interferon regulatory factor 6 (IRF6) variants to the risk of nonsyndromic oral clefts in Asians; however, this has not included the Malay population. The current study attempts to address this research gap using allele and haplotype transmission disequilibrium analyses. The results showed a strong transmission distortion for multiple haplotypes to patients with nonsyndromic cleft lip with or without cleft palate. Haplotypes carrying the 243 bp allele of D1S2136 and common alleles at the rs861019 and rs2235371 were over-transmitted to patients. By contrast, haplotypes consisting of the 251 bp allele of D1S2136 and the rare allele at rs2235371 were more under-transmitted. Furthermore, several variants and haplotypes showed excess maternal transmission, but none of them attained statistical significance in maternal relative risk analyses. In contrast, a significant child genotype effect was observed for several haplotypes, indicating fetal genotype could be the major genetic contribution rather than maternal genotype. The present study therefore further supports a role for IRF6 variants in clefting in this Southeast Asian population. Overall, Asian genetic backgrounds are most likely more susceptible to the haploinsufficiency of IRF6 variants. These variants may contribute to the condition either themselves, or they may be in linkage disequilibrium with other casual variants.

An in Vitro Study of Molecular Effects of a Combination Treatment with Antibiotics and Nanofluid Containing Carbon Nano-tubes on Klebsiella pneumoniae.

BACKGROUND: We aimed to prepare a nanofluid, containing f-MWCNTs, and investigate the antibacterial efficacy of f-MWCNTs+ ciprofloxacin (cip) on Klebsiella pneumoniae by evaluating the virulence gene expression. METHODS: This study was carried out from 2019 to 2020, in the Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran. The nanofluid containing antibiotic and f-MWCNTs were prepared by the ultrasonic method. The minimum inhibitory concentrations (MICs) of ciprofloxacin and f-MWCNTs were determined using the broth micro dilution MIC tests. For examining the antibacterial effects, the expression level of virulence genes, under the influence of f-MWCNTs, was evaluated by a real-time PCR. RESULTS: The effect of 8 µg/ml ciprofloxacin + 400 µg/ml f-MWCNTs, completely inhibited the growth of the resistant isolate of K. pneumoniae, while, in the ATCC 700,603 isolate, 2 µg/ml ciprofloxacin with 100 µg/ml f-MWCNT could inhibit a bacterial growth. In the resistant K. pneumoniae clinical isolate, after f-MWCNT+cip treatment, the expression of fimA, fimD, wza, and wzi genes was significantly downregulated, compared to the ciprofloxacin treatment, and upregulated, compared to the negative control. For the ATCC 700,603 isolate treated with f-MWCNT+cip, the expression of fimA, fimD and wza virulence genes showed upregulation, compared to the negative control and downregulated in comparison with the ciprofloxacin treatment. CONCLUSION: Simultaneous treatment of resistant isolate of K. pneumoniae with f-MWCNTs +antibiotic could improve the effectiveness of antibiotic at lower doses, due to the reduced expression of virulence genes in comparison with antibiotic treatment, besides the increased cell wall permeability to antibiotics.

Maternal uniparental heterodisomy of chromosome 6 in a boy with an isolated cleft lip and palate.

We describe a chromosome 6 uniparental disomy (UPD6) in a boy, discovered during a screening for the genetic cause of cleft lip and palate. In the medical literature, almost all documented cases of UPD6 are paternal in origin, and only four were maternal. We present here a report of complete maternal chromosome 6 uniparental heterodisomy. Haplotype analysis was performed using highly polymorphic short tandem repeat (STR) markers that span both arms of chromosome 6. Analysis of these markers revealed the presence of two maternal alleles but no paternal allele, indicating an instance of maternal uniparental heterodisomy. Chromosome analysis of peripheral blood lymphocytes confirmed a normal male karyotype. Advanced maternal age at the time of the infant's birth and heterodisomy of markers around the centromere favors a meiosis-I error. No specific phenotype has been reported for maternal UPD6. Therefore, the cleft lip and palate in the present case probably occurred due to other risk factors. This report provides further evidence that maternal UPD6 has no specific clinical consequences and adds to the collective knowledge of this rare chromosomal finding.

Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

BACKGROUND: Coronary arteries disease (CAD) has been recognized as one of the most common causes of death worldwide, with an estimated seven million deaths annually. METHODS: Two hundred blood samples from Iranian CAD patients and normal healthy controls were collected. CAD and the 9p21 locus variants rs1333049 and rs10757278 were analyzed for potential associations. RESULTS: No significant differences in rs10757278 and rs1333049 polymorphisms were found between patients and controls, but a significant relationship was found between rs10757278 and rs1333049 in CAD patients at the genotype level (p= 0.0323). At the haplotype level and on the basis of diplotype analysis, a significant relationship was found between patients and controls (OR= 5.16, p= 0.047, 95% CI: 1.02-26.0). In CAD patients, rs10757278 and rs1333049 were associated at locus 9p21. CONCLUSION: The inconsistency between the results of this and other studies on different CAD populations may be due to high population, different ethnicities, low prevalence of some alleles in populations, and interactions of different genes.

The Effect of Hormone Therapy on the Expression of Prostate Cancer and Multi-Epigenetic Marker Genes in a Population of Iranian Patients.

BACKGROUND AND AIM: Many recent studies have shown a direct relationship between the decrease in the expression of GSTP1 and RASSF1 with the incidence and progression of prostate cancer. Moreover, the expression level of these genes is greatly affected by epigenetic factors and their methylation pattern. Given the prevalence of prostate cancer and the importance of choosing the best method to inhibit the progression of the disease and provide specific treatment, it is important to evaluate the effect of hormone therapy on the expression of effective prostate cancer genes and epigenetic markers. PATIENTS AND METHODS: In this case-control study, 35 prostate cancer samples were examined before and after hormone therapy. Following the blood sampling, RNA extraction, and cDNA synthesis, the expression of GSTP1, RASSF1, HDAC, DNMT3A, and DNMT3B was assessed by real-time PCR. RESULTS: The results analysis showed that the expression of GSTP1, RASSF1, and DNMT3B was significantly increased, DNMT3A was significantly decreased (P value<0.05) and HDAC expression did not change significantly (P value=0.19) after hormone therapy. DISCUSSION: Significant changes in the expression of GSTP1, RASSF1, DNMT3B and DNMT3A in the studied samples indicate that these genes are susceptible targets for cancer hormone therapy in Iranian men like in the other populations. Evaluation of gene activity in a larger population of patients may support these findings.