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The aim of this study was to evaluate an engineered nanostructure to silence five important oncogenes, including BAG1, MDM2, Bcl-2, BIRC5 (survivin) and XIAP, in acute myeloid leukemia subtype 2 (AML-M2). The smart nanostructures were functionalized gold nanoparticles (FGNs) containing five antisense oligonucleotides (AOs) and one anti-CD33(+)/CD34(+) aptamer. First, the best AO for each gene was selected with the OligoWalk online software, and then different arrangements of AOs were evaluated with the RNAstructure software. Thereafter, naked gold nanoparticles (NGNs) were synthesized by the reaction of 1000 mm HAuCl4 with 10 μg ml(-1) ascorbic acid. Next, five AOs and one anti-CD33(+)/CD34(+) aptamer were attached to NGNs through serial reactions. Later, 5 ml of heparinized blood samples from five AML-M2 patients were prepared, cancerous cells were isolated and then incubated with three concentrations (75, 150 and 300 μg ml(-1)) each of FGNs, NGNs, gold nanoparticles functionalized with scrambled oligonucleotides (GNFSONs) and doxorubicin. Finally, cell death percentage and gene expressions were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and real-time PCR, respectively. This study showed that FGNs and doxorubicin led to more cell death compared with NGNs and GNFSONs (P<0.05). Interestingly, all concentrations of FGNs led to a decrease in gene expression. As an important finding, although all concentrations of doxorubicin could also inhibit the expression of genes, FGNs had more effect (P<0.05). Moreover, both NGNs and GNFSONs could silence all genes only at a concentration of 300 μg ml(-1). For BCL2 and XIAP, a dose-dependent pattern was observed, but there was no similar pattern for others.

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Background: Phenylketonuria as the most common genetic metabolic disorder is the result of disruption of the phenylalanine hydroxylase gene. This study was carried out to explore the phenylalanine hydroxylase gene mutation status of Iranian phenylketonuria patients. Methods: Blood samples were collected from 30 patients, and hot spot areas of the phenylalanine hydroxylase gene, including exons 6, 7, 8, 11, and 12 were studied through polymerase chain reaction and sequencing techniques. Results: Eight different mutations, including 5 missense mutations, 1 splice mutation, 1 nonsense mutation, and 1 Silent/Splice mutation were detected. These mutations were R243X, R261Q, R261X, P281L, R241C, V399V, E280K, and IVS11+1G>C. V399V and R241C were reported for the first time in Iranian population. Three polymorphisms including Q232Q, V245V and L385L and 3 novel intronic variants including IVS10-15A>C, IVS6+44T>G, and IVS6+36 T>G were also detected in this study. Conclusion: The results of this study prove the heterogeneous status of phenylalanine hydroxylase gene mutations in the Iranian population, which can be useful in carrier testing and genetic counseling.

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Mitochondria have essential role in cellular energy metabolism and defects in their function lead to many metabolic diseases. Mitochondrial DNA (mtDNA) mutations have been associated with number diseases such as nonsyndromic and aminoglycoside-induced hearing loss. Mutational screening of entire 12SrRNA and tRNA (ser (UCN)) genes in 107 unrelated Iranian patients with amino glycoside-induced and nonsyndromic bilateral hearing loss by direct sequencing analysis method were performed. Twenty different homoplasmic sequence variants were identified; including fifteen common polymorphisms, two putatively pathogenic variants: m.921T>C and m.1005T>C, one 12SrRNA sequence variant m.739C>T and two nucleotides substitution; m.1245T>C and m.1545T>C. Deafness-associated mutation, m.1555A>G, was not found. In our patients we found the mutation 1005 was associated with R haplogroup. These finding show that m.1555A>G mutation is not important in our population. Nucleotide change, m.739C>T, previously reported with very low frequency. We suggested the variation of two nucleotides 1245 and 1545 that localized at conserved site of 12SrRNA may be new candidate for amino glycoside-induced and nonsyndromic hearing impairment associated mutations. However, aminoglycoside exposure is a risk factor for clinical phenotype appearance of these mutations.

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