Targeted Gene Delivery to MCF-7 Cells Using Peptide-Conjugated Polyethylenimine

Specific and effective delivery of drugs and genes to cancer cells are the major issues in successful cancer treatment. Recently, targeted cancer gene therapy has been emerged as a main technology for the treatment of different types of cancers. Among various synthetic carriers, polyethylenimine is one of the most well-known polymers for gene delivery. In this study, we conjugated phage-derived peptide (DMPGTVLP) to polyethylenimine (10 kDa) via disulfide bonds for targeted gene delivery into breast adenocarcinoma cells (MCF-7). As negative-control cells, we used non-related hepatocellular carcinoma cells (HepG2). Peptide-conjugated polyplex exhibited low cytotoxicity and significantly increased the transfection efficiency in comparison with unmodified polyethylenimine. Therefore, the peptide-modified vector can be used as a good targeting agent for gene or drug delivery into breast adenocarcinoma cells.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-014-0208-6) contains supplementary material, which is available to authorized users.KEY WORDS: breast cancer, gene therapy, phage-derived peptide, polyethylenimine     

Transforming growth factor beta 1 869T/C and 915G/C polymorphisms and risk of autism spectrum disorders

Background:

Transforming growth factor-β1 (TGF-β1) has been found to play a crucial role in early central nervous system development. Several studies have illustrated decreased TGF-β1 levels in sera and brains of autistic children. Two point mutations in the TGF-β1 signal peptide at 869T/C and 915G/C have been reported to influence TGF-β1 expression. The aim of the present study was to investigate the correlation of TGF-β1 polymorphisms and their haplotypes with autism.

Methods:

This study was performed on 39 autistic patients and 35 age- and sex-matched normal controls in an Iranian population, using the sequence specific primed-polymerase chain reaction (PCR-SSP) technique. Patients were divided into mild-to-moderate and severe groups according to the childhood autism rating scale.

Results:

No significant differences were observed for allele, genotype, or haplotype frequencies between the autistics and controls. Only a slight difference was observed in GC25 between the controls and all children with autism.

Conclusion:

Thus, these results indicate that the polymorphisms in TGF-β1 gene may not play an important role in the development of autism.Key Words: Autism spectrum disorders, Development, Polymorphism, Transforming Growth Factor beta 1     

Production of some benzylisoquinoline alkaloids in Papaver armeniacum L. hairy root cultures elicited with salicylic acid and methyl jasmonate

Papaver armeniacum hairy roots were induced by four Rhizobium rhizogenes strains on three explants (shoot, root, and hypocotyl). Also, the effects of two concentrations (100 and 200 μM) of methyl jasmonate (MJ) and salicylic acid (SA) were assessed on productions of papaverine, noscapine, thebaine, morphine, and codeine and expression of some related genes (TYDC, DBOX, BBE, SalAT, T6ODM, and COR) in P. armeniacum L. hairy root culture at 24 and 48 h after elicitation. R. rhizogenes strain C58C1 induced the highest hairy root rate on hypocotyl explant. Application of 100 μM MJ resulted in the highest contents of thebaine, codeine, and morphine by enhancing the expression of SalAT, COR, and T6ODM genes, respectively, while application of 100 μM SA resulted in the highest contents of papaverine and noscapine by upregulating DBOX and BBE genes, respectively. 100 μM MJ can be used as an effective elicitor in P. armeniacum hairy root culture to increase studied morphinan alkaloids. Also, SA can be suggested for enhancing papaverine and noscapine contents in P. armeniacum hairy root culture. It may be due to that there is a SA- and MJ-signaling crosstalk, which results in reciprocal antagonism between SA and MJ signaling pathways. The effects of MJ and SA elicitors on benzylisoquinoline alkaloids (BIAs) production were level-dependent.

     

Prevalence of ApoB100 rs693 gene polymorphism in metabolic syndrome among female students at King Abdulaziz University

Apolipoprotein B100 (ApoB100) is a glycoprotein and a member of the adipokine family. It plays a central role in lipoprotein metabolism. Many research studies have revealed a strong relation between ApoB100 and metabolic syndrome (MetS) and insulin resistance.In our research, we examined the relationship between ApoB100 rs693 gene polymorphism, body mass index (BMI) and the probability of MetS in young female students studying at King Abdulaziz University (KAU) in Saudi Arabia. The study group comprised 141 females whose ages ranged from 18 to 25 years. Anthropometric measurements and biochemical parameters were measured alongside a genetic analysis of ApoB100 rs693.The BMI, glucose concentration and total cholesterol level were found to be significantly associated with the ApoB100 rs693 gene. The differences noted between control and MetS groups regarding glucose concentrations were statistically significant (P = 0.001).A growing number of young females are being diagnosed with MetS in KAU because of unhealthy eating habits, in combination with the absence of physical exercise, causing increased body weight and the potential progression of chronic diseases. Our study showed that the allele associated with hypertensive individuals at ApoB100 rs693 and MetS may have a direct genetic influence. Further research on expanded sample sizes, however, is required in order to draw rigid conclusions.     

In vivo bone regeneration using a bioactive nanocomposite scaffold and human mesenchymal stem cells

Cell and Tissue Banking - Due to the osteoconductive role of bioceramics, use of these bioactive nanocomposite scaffolds that can maintain their structural integrity during bone tissue...     

Wideband Graphene-Based Fractal Absorber and its Applications as Switch and Inverter

In this paper, the idea of square fractal geometry has been utilized to introduce a tunable wideband graphene-based perfect plasmonic absorber in the near-infrared region. It consists of a MgF₂ layer and an array of gold squares fractal loaded on a graphene layer. In the designed absorber a single layer of graphene has been used instead of multilayered graphene structures. The structure is polarization-insensitive under normal incidence due to the geometric symmetry. The absorption and bandwidth of the structure are almost insensitive to the incident angle up to 15° and 45° for TE and TM polarizations, respectively. Moreover, by choosing appropriate structural parameters, the resonance wavelength of the desired plasmonic absorber can be controlled. The absorption of the introduced structure can be tuned by changing the chemical potential of the graphene. Therefore, the proposed fractal absorber can act as switch and inverter at λ = 1995 nm. Furthermore, the equivalent circuit model of the absorber has been derived to confirm the validity of the simulation results. The superiorities of our fractal absorber are wide full-width at half-maximum of 406 nm, multi-applicant, perfect absorption, and fabrication feasibility due to the simple structure with the maximum absorption tolerance error of 5.12%.

     

Interactions of anthropometric indices,rs9939609 FTO gene polymorphism and breast cancer: A case-control study

Contradictory results were reported on the effect of fat mass- and obesity-associated (FTO) gene and anthropometric measurements on breast cancer (BC). This study aimed to assess the interactions between rs9939609 polymorphism of FTO gene, anthropometric indices and BC risk in Iranian women. This case-control study was performed on 540 women including 180 women with BC and 360 healthy women in Tehran, Iran. Physical activity and dietary intakes were assessed by validated questionnaires. Data on sociodemographic and pathologic factors of the participants as well as their blood samples were collected. The rs9939609 FTO gene polymorphism was genotyped using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). No significant association was found between BC and risk allele of FTO rs9939609 polymorphism after adjustments for the confounders. However, there was a significant association between rs9939609 polymorphism risk allele and BC risk in females with overweight, even after adjusting for age, family history of BC, abortion, BMI and the number of pregnancies (P < .05). The association was disappeared after further adjustments for lifestyle factors including smoking, alcohol consumption, calorie and macronutrients intake, and physical activity. The FTO gene polymorphism was associated with the risk of BC in overweight individuals. This association was influenced by environmental factors including diet, alcohol consumption and smoking. Future studies are required to confirm the association between the FTO gene and BC in overweight females and to identify the underlying mechanisms.     

Effects of a Potential Probiotic Strain Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-Induced Inflammatory Response and Gene Expression in Coinfected Gastric Epithelial Cells

In the present study, we aimed to investigate the modulatory effects of a potential probiotic bacterium Lactobacillus gasseri ATCC 33323 on Helicobacter pylori-induced inflammatory response and gene expression in human gastric adenocarcinoma (AGS) cell line. The gastric epithelial cells were coinfected with a collection of H. pylori clinical strains alone or in combination with L. gasseri at a multiplicity of infection (MOI) of 1:100 for each bacterium, and incubated for different time points of 3, 6, and 12 h. IL-8 secretion from coinfected AGS cells after incubation at each time point was measured by an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-8, Bcl-2, β-catenin, integrin α₅, and integrin β₁ genes was determined by quantitative RT-PCR amplification of total RNA extracted from coinfected epithelial cells. L. gasseri significantly (P < 0.05 and P < 0.01) decreased the production of IL-8 in AGS cells coinfected with H. pylori strains at 6 h post-infection. We also detected that L. gasseri significantly (P < 0.05) down-regulated the gene expression level of IL-8 in H. pylori-stimulated AGS cells after 6 and 12 h of coinfection. Similarly, L. gasseri caused a significant decrease (P < 0.05) in mRNA expression of Bcl-2, β-catenin, integrin α₅, and integrin β₁ genes in AGS cells at 3 and 6 h after infection with H. pylori strains as compared with non-infected control cells. In conclusion, our results demonstrated that L. gasseri ameliorates H. pylori-induced inflammation and could be developed as a supplementation to the current treatment regimens administrated against H. pylori infection.

     

The effect of aflibercept and arsenic trioxide on the proliferation,migration and apoptosis of oral squamous cell carcinoma in vitro

Molecular Biology Reports - Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs,...