GL-9 peptide regulates gene expression of CD44 cancer marker and pro-inflammatory cytokine TNF-α in human lung epithelial adenocarcinoma cell line (A549).

In this study, we examined cytotoxic effect of GL-9 peptide on A459 cell line through studying the changes in TNF-α and CD44 gene expression and ROS production. Real-time PCR analysis showed that the treated A549 cells highly over expressed TNF-α, which was associated with a significant reduction of CD44 gene expression levels (p  <  0.05). ROS production rate was measured through the usage of DCFH-DA primer. Results demonstrated that GL-9 peptide could also induce cell death via ROS production. The effect of GL-9 peptide on human erythrocytes and leukocytes was analyzed. GL-9 peptide showed no significant toxic effect on human blood cells. Our results suggested that the GL-9 peptide as a potent natural agent could modulate gene expression of cancer cell markers.

Combination of auraptene and arsenic trioxide induces apoptosis and cellular accumulation in the subG1 phase in adult T-cell leukemia cells.

Objectives: Despite advances in the treatment of adult T-cell leukemia/lymphoma (ATLL), the survival rate of this malignancy remains significantly low. Auraptene (AUR) is a natural coumarin with broad-spectrum anticancer activities. To introduce a more effective therapeutic strategy for ATLL, we investigated the combinatorial effects of AUR and arsenic trioxide (ATO) on MT-2 cells. Materials and Methods: The cells were treated with different concentrations of AUR for 24, 48, and 72 hr, and viability was measured by alamarBlue assay. Then, the combination of AUR (20 µg/ml) and ATO (3 µg/ml) was administrated and the cell cycle was analyzed by PI staining followed by flow cytometry analysis. In addition, the expression of NF-κB (REL-A), CD44, c-MYC, and BMI-1 was evaluated via qPCR. Results: Assessment of cell viability revealed increased toxicity of AUR and ATO when used in combination. Our findings were confirmed by accumulation of cells in the sub G1 phase of the cell cycle and significant down-regulation of NF-κB (REL-A), CD44, c-MYC, and BMI-1. Conclusion: Obtained findings suggest that combinatorial use of AUR and ATO could be considered for designing novel chemotherapy regimens for ATLL.

Investigating the effect of aqueous extract of Chicorium intybus L. leaves on offspring sex ratio in rat.

A traditional belief in Iranian culture indicates that parental consumption of chicory leaves (Chicorium intybus L.) affects the gender of newborns. The aim of this study was to investigate the effect of aqueous extract of chicory on offspring sex ratio in rat. All rats in experimental groups 1 and 2 were i.p. injected with either 1.0 or 0.7 g/kg body weight (LD50 = 2.244 g/kg) of an aqueous extract of chicory leaves for 30 days at 72 h intervals. The control rats were injected with distilled water in the same manner. After the 8th injection, blood pH, and Na(+), K(+), Ca(2+) and Mg(2+) serum levels, were measured in all groups. On day 30, all the rats were mated within and between groups. The results revealed that in comparison with the control group, there were significant increases (p < 0.01) in Na(+) and K(+) levels, as well as the sex ratio of male to female offspring (10.23%) in experimental group 1. Therefore, it can be concluded that the administration of chicory leaf extract has a significant effect on the sex ratio of the rat offspring.

The enhancement of vincristine cytotoxicity by combination with feselol.

Urinary bladder cancer is one of the most common cancers worldwide. Human transitional cell carcinoma (TCC) cells are epithelial-like adherent cells originally established from a primary bladder carcinoma. Studies have shown that TCC cells are resistant to some chemotherapeutic agents such as vincristine (VCR). In the present study, the effect of feselol, a sesquiterpene coumarin isolated from the fruits of Ferula badrakema, was investigated on VCR effectiveness. Our results demonstrated that feselol itself did not have any cytotoxic effect on TCC cells. In order to check its combinatorial effects, TCC cells were exposed to various combined concentrations of feselol and VCR. Then, morphological changes were monitored and cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay for three consequent days. Results showed that the combination of 40 microg/ml VCR with 16 microg/ml feselol increased the cytotoxicity of VCR by 28.32% after 48 h. This effect might be due to inhibition of P-glycoprotein in TCC cells by feselol.

The effects of lead on the development of somites in chick embryos (Gallus gallus domesticus) under in vitro conditions: a histological study.

Lead (Pb) is one of the most abundant toxic metals in the environment that can cause a variety of harmful effects. During embryonic development of vertebrates, somites are temporary organs that give rise to skeletal muscle, cartilage, tendon, endothelial cells, and dermis. In this study, we investigated the effects of lead on the development of somites and their derivatives in chick embryos under in vitro conditions. For this propose, fertilized eggs of Gallus gallus domesticus were incubated until they reached the stage of 15-20 somites. The somites and notochord were isolated and treated with different concentrations of lead acetate (500, 1000, 2000, and 4000 ng ml-1) for 72 h. Our results indicated that high concentrations of lead reduced the nucleus diameter, reduced the synthesis of collagen, inhibited the formation of the cartilage matrix in somite cells, and disturbed the formation and order of myotubes. In conclusion, the results of the current study for the first time indicated the disturbing effects of lead on the development of somites in the chick embryo. Our results revealed that lead disturbed the development of somites in the chick embryo, which suggested that at high concentrations it can cause a serious mortal danger to life.

A transient insulin system dysfunction in newborn rat brain followed by neonatal intracerebroventricular administration of streptozotocin could be accompanied by a labile cognitive impairment.

The early postnatal period is a critical period of hippocampus development, which is highly dependent on insulin receptor (IR) signaling and very important in cognitive function. The present study was conducted in order to present a model of neonatal transient brain insulin system dysfunction through finding an appropriate dose of injection of streptozotocin (STZ) during the neonatal period. Sixty male Wistar rat pups were divided into 4 groups of 15 and received intracerebroventricular saline or STZ (icv-STZ) (15, 20 and 25µg/kg) on postnatal day 7. Gene expression of IR and target genes for IR signaling (choline acetyltransferase (ChAT) and Tau) were measured at the ages of 2 and 7 weeks. Behavioral tests were performed at the ages of 3 and 6 weeks to assess short- and long-term cognitive function. 20µg/kg dose of icv-STZ was estimated as the optimal dose causing transient alteration in gene expression of IR, ChAT and Tau. Additionally, cognitive function of the animals restored to normal level at the age of 6 weeks. Therefore, 20µg/kg dose of icv-STZ is proposed as a new approach to generating transient brain insulin system dysfunction associated with transient cognitive impairments at a critical postnatal period of brain development.