DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Background: Schizophrenia, schizoaffective disorder, and bipolar illness are common psychological disorders with high heritability and variable phenotypes. The disrupted in schizophrenia 1 ( DISC1) gene, on chromosome 1q42, has an essential role in neurite outgrowth and cell signaling. The purpose of this study was to investigate the association of three single-nucleotide polymorphisms (SNPs; rs6675281, rs2255340, and rs2738864) with schizophrenia disorder. These three SNPs were chosen as they had been used in most of the previous studies. Methods: In a case-control study of Iranian population for the first time 778 blood samples were collected including, 402 schizophrenic patients and 376 healthy controls. Genomic DNA was extracted from peripheral blood using DNA extraction kit (BioFlux Co). The genotypes of rs6675281, rs2255340, and rs2738864 were detected by nested allele-specific multiplex polymersae chain reaction (PCR). Results: Our data revealed that the three SNPs are significantly associated with schizophrenia (rs2255349 C>T: confidence interval (CI), 2.115 to 3.268; P = 0.0000 OR: 2.629; rs2738864 C>T: CI, 1.538 to 2.339; P = 0.0000 OR: 1.897; rs6675281 C>T: CI, 2.788 to 4.662; P = 0.0009241 OR: 3.605). Through applying the expectation-maximization (EM) algorithm, we calculated the haplotype frequency, and finally performed haplotype analysis with Bonferroni correction and data preprocessing methods and the results showed rs66875281 to have the highest association. Discussion: Our findings primarily showed that DISC1 gene polymorphisms contribute to schizophrenia risk and have a significant association with this disorder among Iranian population. The strategy was found to be easy, rapid, specific, and consistent for the co-occurring detection of the DISC1 polymorphisms. We could finally confirm that the polymorphisms are related to schizophrenia studied in Iranian population.     

2q35-rs13387042 variant and the risk of breast cancer: a case–control study

Molecular Biology Reports - Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease...     

Association between serum cell adhesion molecules with hs-CRP,uric acid and VEGF genetic polymorphisms in subjects with metabolic syndrome

Molecular Biology Reports - Metabolic syndrome (MetS) is associated with a pro-inflammatory state and endothelial dysfunction that places subjects with MetS at a higher risk of atherosclerosis....     

Inhibition of hydrogen sulfide production by gene silencing attenuates inflammatory activity of LPS-activated RAW264.7 cells

Hydrogen sulfide is an inflammatory mediator and is produced by the activity of the enzyme cystathionine γ-lyase (CSE) in macrophages. Previously, pharmacological inhibition of CSE has been reported to have conflicting results, and this may be due to the lack of specificity of the pharmacological agents. Therefore, this study used a very specific approach of small interfering RNA (siRNA) to inhibit the production of the CSE in an in vitro setting. We found that the activation of macrophages by lipopolysaccharide (LPS) resulted in higher levels of CSE mRNA and protein as well as the increased production of proinflammatory cytokines and nitric oxide (NO). We successfully used siRNA to specifically reduce the levels of CSE mRNA and protein in activated macrophages. Furthermore, the levels of proinflammatory cytokines in LPS-activated macrophages were significantly lower in siRNA-transfected cells compared to those in untransfected controls. However, the production levels of NO by the transfected cells were higher, suggesting that CSE activity has an inhibitory effect on NO production. These findings suggest that the CSE enzyme has a crucial role in the activation of macrophages, and its activity has an inhibitory effect on NO production by these cells.     

Bioprocess engineering of <Emphasis Type="Italic">Echium italicum</Emphasis> L.: induction of shikonin and alkannin derivatives by two-liquid-phase suspension cultures

An in vitro cell suspension culture of Echium italicum was established and assayed for the production of shikonin and alkannin derivatives. Callus tissues were induced from cotyledon explants of the plant incubated onto the solidified B5 medium. A two-liquid-phase system suspension culture was then established to elicit pigments of shikonin and alkannin derivatives using liquid paraffin. The presence of liquid paraffin efficiently induced production of pigments in cultured cells. The production and/or accumulation of these compounds in the E. italicum cells was examined using fluorescence microscopy as the naphthoquinone molecules display autofluorescent properties. Phytochemical analysis of the n-hexane extract of the medium was also carried out using preparative HPLC. The chemical structure of shikonin and alkannin derivatives were characterized by UV, 1H-NMR, and 13C-NMR techniques. Based on our findings, this bioprocess engineering approach resulted in induction of shikonin and alkannin derivatives, whereupon it may be recruited for production of these important secondary metabolites.     

Aggregation and Amyloid Fibril Formation Induced by Chemical Dimerization of Recombinant Prion Protein in Physiological-like Conditions

Prion diseases are caused by the conversion of a cellular protein (PrP^C) into a misfolded, aggregated isoform (PrP^Res). Misfolding of recombinant PrP^C in the absence of PrP^Res template, cellular factors, denaturing agents, or at neutral pH has not been achieved. A number of studies indicate that dimerization of PrP^C may be a key step in the aggregation process. In an effort to understand the molecular event that may activate misfolding of PrP^C in more relevant physiological conditions, we tested if enforced dimerization of PrP^C may induce a conformational change reminiscent of the conversion of PrP^C to PrP^Res. We used a well described inducible dimerization strategy whereby a chimeric PrP^C composed of a modified FK506-binding protein (Fv) fused with PrP^C and termed Fv-PrP is incubated in the presence of a monomeric FK506 or dimerizing AP20187 ligand. Addition of AP20187 but not FK506 to recombinant Fv-PrP (rFv-PrP) in physiological-like conditions resulted in a rapid conformational change characterized by an increase in β-sheet structure and simultaneous aggregation of the protein. Aggregates were partially resistant to proteinase K and induced the conversion of soluble rFv-PrP in serial seeding experiments. As judged from thioflavin T binding and electron microscopy, aggregates converted to amyloid fibers. Aggregates were toxic to cultured cells, whereas soluble rFv-PrP and amyloid fibers were harmless. This study strongly supports the proposition that dimerization of PrP^C is a key pathological primary event in the conversion of PrP^C and may initiate the pathogenesis of prion diseases.     

Salicylic acid improves podophyllotoxin production in cell cultures of Linum album by increasing the expression of genes related with its biosynthesis

Treatment of Linum album cell cultures with 10 μM salicylic acid (SA) for 3 days improved podophyllotoxin (PTOX) production up to 333 μg/g dry weight (DW): over three times that of the control cultures. qPCR analyses showed that in SA-treated cells, the expression of the genes coding for phenylalanine ammonia-lyase (PAL), cinnamoyl-CoA reductase (CCR) and cinnamyl-alcohol dehydrogenase (CAD), all involved in the first steps of PTOX biosynthesis, also increased reaching a peak 8–12 h after the treatment. Expression of the pinoresinol-lariciresinol reductase gene (PLR), which is involved in one of the last biosynthetic steps, was not affected by SA. The selective action of SA on these genes can be applied to control the biotechnological production of this anticancer agent.     

Aqueous humor nitric oxide in patients with central retinal vein occlusion

PurposeIt has been suggested that nitric oxide (NO) has a role in ischemic retinopathies. Since retinal ischemia may develop in retinal vein occlusion, we investigated the presence of nitric oxide in the pathogenesis of central retinal vein occlusion (CRVO).MethodsEighteen consecutive patients with CRVO were included in this study. Aqueous humor specimens were obtained within 21 days of diagnosis. Samples of aqueous humor were also collected from 20 control patients undergoing cataract surgery. For each sample after reduction of nitrate to nitrite with vanadium chloride (VCl₃), we used spectrophotometric method for simultaneous detection of nitrate and nitrite (NO_x).ResultsMean level of aqueous humor NO_x in CRVO and control group was 94.1 ± 23.2 μmol/l and 55.6 ± 11.0 μmol/l, respectively. The difference between two groups was statistically significant (p < 0.0001).ConclusionsOur results may support involvement of nitric oxide in the pathogenesis of CRVO.     

Imaging of human glioma cells by means of a Syndecan-4 directed DOTA-conjugate

The extracellular glycoprotein Tenascin-C (TN-C) is highly upregulated in gliomas. Therefore, many chemotherapies with radiolabeled antibodies against TN-C have been performed. However, TN-Cs binding partner Syndecan-4 did not play any role as a therapeutic or imaging target in gliomas. We constructed an imaging compound containing the magnetic resonance imaging (MRI) contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the fluorescence dye sulforhodamine and a synthetic Syndecan-4-specific 21 amino acid peptide derived from TN-C. Magnetic resonance relaxometry, confocal laser scanning microscopy, and flow cytometry showed that the Syndecan-4-DOTA-Rhodamine conjugate was taken up into the cytoplasm of human U373 glioma cells without any cytotoxic effects. Competition experiments indicate that this uptake was receptor-mediated. This conjugate might be used for future MRI studies of brain tumors after systemic or intraoperative local application.