Phorbol ester TPA modulates chemoresistance in the drug sensitive breast cancer cell line MCF-7 by inducing expression of drug efflux transporter ABCG2

Recent studies have indicated a link between levels of cyclooxygenase-2 (COX-2) and development of the multidrug resistance (MDR) phenotype. The ATP-binding cassette sub-family G member 2 (ABCG2) is a major MDR-related transporter protein that is frequently overexpressed in cancer patients. In this study, we aimed to evaluate any positive correlation between COX-2 and ABCG2 gene expression using the COX-2 inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) in human breast cancer cell lines. ABCG2 mRNA and protein expression was studied using real-time RT-PCR and flow cytometry, respectively. A significant increase of COX-2 mRNA expression (up to 11-fold by 4 h) was induced by TPA in MDA-MB-231 cells, this induction effect being lower in MCF-7 cells. TPA caused a considerable increase up to 9-fold in ABCG2 mRNA expression in parental MCF-7 cells, while it caused a small enhancement in ABCG2 expression up to 67 % by 4 h followed by a time-dependent decrease in ABCG2 mRNA expression in MDA-MB-231 cells. TPA treatment resulted in a slight increase of ABCG2 protein expression in MCF-7 cells, while a time-dependent decrease in ABCG2 protein expression was occurred in MDA-MB-231 cells. In conclusion, based on the observed effects of TPA in MDA-Mb-231 cells, it is proposed that TPA up-regulates ABCG2 expression in the drug sensitive MCF-7 breast cancer cell line through COX-2 unrelated pathway

Study of aqueous extract of three medicinal plants on cell membrane–permeabilizing and their surface properties

The aim of this study was to evaluate the effect of aqueous extract of three medicinal plants, Artemisia dracunculus L, Cuminum cyminum L and Heracleum persicum Desf, which contain saponins on biological membrane. Also in this study, some of their physicochemical properties were studied. At the first step, the aqueous extract of the plants were prepared, using maceration and then the extracts were lyophilized. 0.2 ml of RBC was added to 0.2 ml of different concentrations of each extract in McIvan’sbuffer, and then incubated in two different times and temperatures. The absorbance of the samples was determined by UV spectrophotometer. Among the three studied extracts, A. dracunculus L showed thehighest hemolytic effect and the Heracleum persicum Desf showed the lowest one. The values of emulsification Index (E24) and foam formation activity (Fh) showed for each extract the properties of surface activity. Regarding the results of this study, when considering the health of consumer, the use of aqueous extract of H. persicum Desf, with low hemolytic effect is preferred in pharmaceutical preparation. But if the hemolytic effect were considered, the use of aqueous extract of A. dracunculus L, with great hemolythc effect in comparison to the two other extract, is preferred

Evaluating the toxicity of permeability enhanchers of polyethylene glycol brij ethers surfactants group on cellular membranes and some of their physicochemical properties

The aim of this study is to evaluate the effect of polyethylene glycol brij ethers surfactants group on red blood cells as a model for biological membranes. Also in this study, physicochemical properties including emulsification index (E24), foam producing activity (Fh) and critical micelle concentration (cmc) were studied. Surfactant solutions were prepared in McIvan’s buffer in specific concentrations. 0.2 ml of red blood cells (RBC) was mixed with 0.2 ml of each surfactant solution. The four surfactant solutions had each been incubated differently at two different temperatures for three different times. Each test was done six times. The results were presented as mean absorbance ± the standard deviation. E24, Fh and cmc were also determined for each surfactant solution. All of the surfactant solutions showed hemolytic activity. In comparison with the four studied surfactants, brij 56 had the highest hemolytic effect and brij 72 the lowest. The values of E24 and Fh had good correlation with hydrophilic-lipophilic balance values. According to the results of this study, brijs should be used at concentrations lower than cmc in formulations. Also, according to the results, the use of brijs with low hemolytic effect such as brij 72, is preferred in pharmaceutical preparations.Key words: Brij, biological membrane, hemolysis, hydrophile-lipophile balance (HLB)

Molecular identification and phylogenetic classification of Leishmania spp. isolated from human cutaneous leishmaniasis in Iran: A cross-sectional study

Background: In Iran, both forms of cutaneous (CL) and visceral leishmaniasis (VL) have been reported; so the accurate species identification of the parasite(s) and the analysis of genetic diversity are necessary. Methods: The smears were collected from lesions samples of 654 patients with CL, who attended local health centers in 12 provinces of Iran during 2013-2015. The smears were checked for the presence of amastigotes by light microscopy. DNA of 648 Leishmania isolates, amplified by targeting a partial sequence of ITS (18S rRNA�ITS1�5.8S rRNA�ITS2) gene. Twenty-five of all the amplicons were sequenced and analyzed with restriction fragment length polymorphism (RFLP) using the Taq1 enzyme. Results: All the smears were positive microscopically. The PCR-RFLP analysis revealed that 176 (27) CL patients were infected with L. tropica and, 478 (73) with L. major. The dominant species in all over Iran is L. major. The sequencing results of all CL patients and RFLP analysis confirmed each other. Based on our phylogenetic tree, 25 ITS DNA sequences were grouped into two clusters representing L. major and L. tropica species. Phylogenetic tree derived from the ITS sequences supports a clear divergence between L. major from the other species. Conclusion: Discrimination of Iranian Leishmania isolates using ITS gene gives us this opportunity to detect, identify, and construct the phylogenetic relationship of Iranian isolates. © 2018, Tehran University of Medical Sciences (TUMS). All rights reserved

Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran

Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non-syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease-causing variants in known deafness-associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness-associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30 of our study cohort using ES. This study corroborates the observation that high-throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL. © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

ANTIVIRAL ACTIVITY OF EUPHORBIA MICROSCIADIA EXTRACT

In traditional medicine, the extracts of different species of Euphorbia have been successfully used for the treatment of skin diseases. Therefore, the antiviral effects of Euphorbia microsciadia extracts were investigated using a plaque reduction assay. Plant material was collected, dried and ground and extracted either with methanol using a Soxhlet apparatus or by maceration in methanol. After applying several enriching stages of phage CP51, phage titration was performed to determine the phage concentration in phage lysate for specifying the dilution factor of the phage to be used as negative control for the next working stages. Then IC50 of trifluridine, as a positive control, for phage CP51 was determined. The MIC of the extracts for Bacillus cereus was determined as 1.25 and 0.5 mg/ml for Soxhlet and maceration extracts, respectively, To determine whether the extracts have the ability to inhibit the adsorption of virus to host cell, it was pre-incubated with phage CP51 for 30 min at 25ºC. The growth and reproduction of phage was inhibited by more than 50% at concentration of 1 and 0.25 mg/ml, respectively. In order to test the effects of extract on the transcription process, Bacillus cereus, phage CP51 and extract were incubated together. The growth and reproduction of phage was inhibited by more than 50% at concentration of 0.75 and 0.125 mg/ml for Soxhlet and macerated extracts, respectively. These results indicated that both extracts of E. microsciadia have considerable antiviral activity

Constrained clipping for peak power reduction of multicarrier systems by tone reservation

In this paper we introduce a new method to limit the peak factor of a multicarrier signal based on tone reservation. A peak-reducing signal is computed by clipping the original OFDM symbol. The peak-reducing signal is forced to have the constraints of tone reservation, so that when added to the original signal, the peak factor is reduced without increasing the BER and the out-of-band radiation. The proposed method has low computational complexity requirements and is fast-converging. Moreover, simulation results show that it has higher PAPR-reduction capabilities than other PAPR-reducing methods based on TR in the literature. © 2007 IEEE