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Background: Ceranib-2, an acid ceramidase (AC) inhibitor, can inhibit cancer cell proliferation and tumor development. However, poor water solubility and low cellular bioavailability limit its efficacy in cancer treatment. Methods and results: This study aimed to investigate the cell death induced by ceranib-2 and its solid lipid nanoformulation (ceranib-2-SLN) produced by the hot homogenization technique and the synergistic relationship between ceramide and telomerase in vitro and in silico. Furthermore, this study proved the possible mechanism of ceranib-2-induced AC inhibition by in silico studies. The effective cytotoxic concentrations of ceranib-2, telomerase level, and changes in ceramide levels were measured by MTT colorimetric cytotoxicity assay, ELISA, and LC/MS/MS methods, respectively. TEM results showed that ceranib-2-SLN was 13-fold smaller than the size of ceranib-2. Ceranib-2 and ceranib-2-SLN had IC50 concentrations of 31.62 (± 2.1) and 27.69 (± 1.75) µM in A549, and 48.79 (± 1.56) and 67.98 (± 2.33) in Beas-2B cells. These compounds simultaneously increased ceramide levels and decreased telomerase levels in A549 cells. Ceranib-2 increased telomerase levels while decreasing ceramide levels in Beas-2B cells. It was shown how the synergistic impact of ceranib-2-induced ceramide production and ceramide-induced telomerase level reduction on cytotoxicity in A549 cells. Conclusions: Ceranib-2-SLN was discovered to be more cytotoxic on cancer cells than ceranib-2, suggesting that it could be a promising option for the development of a new anti-cancer agent. [ABSTRACT FROM AUTHOR]

Sigma-1 receptor (SIG1R) is a chaperone that modulates inositol 1,4,5-trisphosphate receptor type1 (IP3R1) calcium (Ca2+) channels on the endoplasmic reticulum. Therefore, SIG1R functions as an indirect regulator of Ca2+ and acts as an apoptosis modulator. Increased expression of SIG1R is associated with poor prognosis in breast cancers (BC), and SIG1R antagonists like BD1047 induce apoptosis. As a heavy metal, cadmium (Cd2+) is competitive with Ca2+ due to its physicochemical similarities and may trigger apoptosis at low concentrations. Our study investigated the SIG1R protein expression in 74 BC patients and found a significant increase in SIG1R expression in the triple-negative BC subtype. We also examined the apoptotic and anti-cancer effects of BD1047 in combination with CdCl2 in MCF7 and MDA-MB-213 cells. Cells were treated with CdCl2 at doses of 1 μM, 25 μM, and 50 μM, along with BD1047. Higher doses of CdCl2 were cytotoxic on both cancer cells and significantly increased DNA breaks. However, low-dose CdCl2 with BD1047 increased cell death and the apoptotic index in BC cells, although it did not exhibit cytotoxic effects on HUVEC cells. Co-administration of low-dose CdCl2 with BD1047 also reduced the migration and colony-forming ability of BC cells. Moreover, the expression of SIG1R protein in these groups decreased significantly compared to groups treated with BD1047 or low-dose CdCl2 alone. In conclusion, low-dose CdCl2 is thought to increase the apoptotic ability of BD1047 in BC cells by reducing SIG1R expression. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO-NPs) are metal oxide NPs that have high cytotoxicity on cancer cells and low cytotoxicity on healthy cells. Breast cancer is the most frequent type of cancer-causing death among women worldwide. In this study, anti-cancer effects of ZnO-NPs were investigated. For this purpose, we treated the MCF7 and MDA-MB-231 breast cancer cell lines and human umbilical vein endothelial cells HUVEC cell line with 10 μg/mL and 20 μg/mL ZnO-NP. Anti-cancer effects of ZnO-NPs were evaluated with cell viability, apoptotic index and colony formation assays, and anti-Warburg effect were investigated by evaluating of pyruvate dehydrogenase (PDH) and Lactate Dehydrogenase A (LDHA) protein expressions. Results indicated that, ZnO-NP application did not have a cytotoxic effect on HUVEC cells, it had cytotoxicity on both breast cancer cell lines. However, MCF7 cells were more sensitive to ZnO-NP treatment. Administration of 20 μg/mL ZnO-NP reduced the survival of MCF7 cells by 62% and increased the apoptotic index by approximately 6 times. Additionally, ZnO-NP treatment inhibited the doubling times of cells and suppressed the colony-forming abilities of both breast cancer cell lines. Also, it was seen that ZnO-NP treatment increased PDH expression in MCF7 cells, where the apoptotic index was more induced. As a result, we have shown for the first time that ZnO-NPs affect the energy metabolism of cells by increasing PDH expression in MCF7 cells, thus increasing the apoptotic index. Our study, which observed the anticancer effects of ZnO-NPs on breast cancer cells, will also shed light on future experimental studies. [ABSTRACT FROM AUTHOR]

West Nile virus (WNV), a member of the Flaviviridae, is a major arbovirus that causes West Nile fever. Previous data showed the prevalence of the WNV serologically and molecular in Turkey, and the presence of lineage 1 in horses and humans has been reported. This is the first notification of partial phylogeny of WNV detected in donkeys in the northeast of Turkey (on the Iranian border). Blood serum samples collected from 25 donkeys without clinical symptoms were tested by RT-PCR. Sequence analysis of the sample detected as positive was performed. Multiple sequence alignments of reference sequences taken from GenBank were performed using the ClustalW method using the MEGA6 program. Partial nucleotide sequences of the capsid gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. According to the phylogenetic tree, the TUR/Igdir/donkey strain was included in the same cluster as the strain (KJ958922) previously obtained from horses in Turkey and the strain (GQ851658) from the Central African Republic. This study is the first report to show the circulation of WNV lineage 1 in donkeys in Turkey. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the mRNA expression profiles of TRAIL-mediated cell death related genes of the hypoxia-tolerant rodent Nannospalax nehringi under hypoxia. The nucleotide and amino acid sequences of these genes were identified. Captured Nannospalax nehringi were randomly divided into normoxia and hypoxia groups. The hypoxia group was exposed to a 7% O2 + 93% N2 gas mixture for 52 h, while animals in the normoxia group were housed under normoxic conditions. Total RNAs were isolated from brain and lung tissues. The cIAP-1, cIAP-2, XIAP, DcR1, DcR2, FLIP and OPG genes were PCR amplified, and the cIAP-1, cIAP-2, XIAP, OPG, TRAIL and FLIP genes were sequenced. Sequenced genes were translated into amino acid sequences and compared with reliable sequences of closely similar species. The genes in the brain were regulated for protection against hypoxia; however, the genes in the lung were regulated differently. Many mutations and insertions were observed on the conserved regions of the cIAP-1, cIAP-2, XIAP, OPG and TRAIL genes in N. nehringi. We propose that these gene mutations and insertions contribute to the anti-hypoxic properties of N. nehringi. [ABSTRACT FROM AUTHOR]

Copyright of Kafkas Universitesi Veteriner Fakultesi Dergisi is the property of University of Kafkas, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As one of the most important components copying DNA molecules in the PCR system, Taq DNA polymerase has a high processivity, however, lower persistence when compared to other polymerases. Studies for the enhancement of stability of Taq DNA polymerase is of great importance. The present study describes the integration of PCR application of cross-linked Taq DNA polymerase enzyme in a nanochamber using a ruthenium based MATyr-Ru-(bipyr)2)-MATyr monomer hapten prepared by photosensitive microemulsion polymerization technique. The conjugation and cross-linking have achieved using our previously invented Aminoacid (monomer) Decorated and Light Underpining Conjugation Approach (ANADOLUCA) method. Microemulsion polymerization media has prepared by dispersing PVA in deionized water. The nano enzyme could be easily prepared at room temperature, in daylight and under nitrogen atmosphere using ruthenium based photosensitive cross-linking agents. The nano copy machine particles (nano Taq DNA polymerase) are very stable against more acidic or more basic conditions, high temperatures and could be reusable in PCR analysis for many times without any deformation in their structures. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:119-123, 2015 [ABSTRACT FROM AUTHOR]

Copyright of Kafkas Universitesi Veteriner Fakultesi Dergisi is the property of University of Kafkas, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Glutathione S-transferase (GST) is the one of most widely used affinity tags in biotechnology applications. The present study named a GST gene as the TtGSTz1 gene, characterized with the conserved glutathione binding motif (SSTSWRVRIAL) under a GST zeta subfamily from Tetrahymena thermophila. Phylogenetic analysis of the TtGstz1p protein sequence, with its orthologs from different GST classes, showed that it is a member of the unicellular GSTz monophyletic clade, which is positioned close to the bacterial GSTz clade. Seven codons of the TtGSTz1 gene were first engineered by introducing silent mutations (TAA > CAA or TAG > CAG) to the code for glutamine instead of stop signals in E. coli. The recombinant TtGSTz1 gene, with its 6XHis tag, was expressed using the pET16b expression plasmid and E. coli BL21(DE3). SDS-PAGE analysis of the 6XHis-TtGstz1p protein confirmed its expression and purification by nickel agarose and glutathione-sepharose 4B. Additionally, both anti-His and anti-GST antibodies recognized the purified 6XHis-TtGSTz in the western blot analysis. In conclusion, the results presented here suggest that the 6XHis- TtGstz1p fusion protein could be used as a dual tag in Tetrahymena expression vectors with a sequential 2-step protein purification procedure. [ABSTRACT FROM AUTHOR]