Genome-Wide Analysis of Alternative Splicing in Zea mays during Maize Iranian Mosaic Virus Infection

Plant Molecular Biology Reporter - Maize Iranian mosaic virus (MIMV) infects several gramineous plants and is an economically important nucleorhabdovirus in Iran. Maize responds to MIMV infection...     

Signaling Crosstalk of FHIT,p53, and p38 in etoposide-induced apoptosis in MCF-7 cells

Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage-induced apoptosis are not well described. In the present study, we used etoposide-induced DNA damage in MCF-7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide-induced DNA damage compared to wild-type cells. However, FHIT knockdown blocked p53 expression, delayed p38 activation, and completely inhibited etoposide-induced apoptosis. Inhibition of p38 activity prevented induction of p53, FHIT, and apoptosis in this model. Thus, activation of p38 upon etoposide treatment leads to increase in FHIT and p53 expression. In p53 knockdown MCF-7, the FHIT induction was hampered but p38 activation was induced in lower doses of etoposide. In p53 knockdown cells, inhibition of p38 induced FHIT expression and apoptosis. Our data demonstrated that the exposure of MCF-7 cells to etoposide increases apoptosis through a mechanism involving the activation of the p38-FHIT-p53 pathway. Moreover, our findings suggest signaling interaction for these pathways may represent a promising therapy for breast cancer.     

A new species of the genus <Emphasis Type="Italic">Allothrombium</Emphasis> (Acari: Trombidiidae) from Montenegro

Allothrombium clavatum sp. n. with reduced inner claw of tarus III, one seta on coxa II, clavate dorsal idiosomal setae and 3-lobed posterior margin of scutum, collected as ectoparasite of an undetermined aphid, is described and illustrated from the central part of Montenegro (Balkan Peninsula). A key to world species of Allothrombium (larva) is presented.     

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.