Search

Alzheimer's disease is a progressive neurodegenerative disorder causing common health problem with increasing age. Evidences show that the key symptoms of AD are mainly caused by cholinergic system dysfunction which has a role in cognitive disorders. Cholinergic pathways especially muscarinic receptors like M1 subtype also have a major role in learning, memory, cognitive functions and emotional state. There is no available permanent treatment currently to cure AD or to change its progression. This study was designed to investigate the factors that play important role in pathogenesis of AD and to compare the effects of Galantamine treatment with effects of Myrtus communis treatment. The expression level of M1, ACh, BDNF; AChE activity, GSH level, MDA and MPO activity and AChE gene expression were investigated in scopolamine-induced rat model. Results showed that, administration of MC significantly improves the SCOP-induced reduction of latency and object recognition time; increasing BDNF, M1 and ACh receptor expression levels in the different brain regions. Additionally, MC showed an increased in AChE by enhancing GSH activity and reducing MDA level and MPO activity. In conclusion MC considered as a possible novel therapeutic approach that can be a valuable alternative way in the prevention and treatment of AD.

In the 21st century, cancer is seen as the biggest obstacle to the prolongation of life expectancy and the most important cause of death in every country in the world. According to the GLOBOCAN 2018 report produced by the International Agency for Research on Cancer (IARC), it is predicted that 18.1 million new cancer cases will be diagnosed based on all age groups and genders for 2018 and approximately 9.6 million people will die due to cancer. Considering all these situations, as well as the studies to increase the effectiveness of classical methods for cancer treatment, the search for alternative treatment methods have been accelerated. High Intensity Focused Ultrasound (HIFU) is a promising method for cancer researchers in recent years. Dosimetric studies are required for the widespread use of HIFU in the clinic. In this study, temperature characterization results, which are the basis of our research for the application of HIFU with dosimetric approach to colon cancer cell lines, are given. &nbsp

Regulation of telomerase activity is thought to participate in the cellular response to ionizing radiation. Epigenetic mechanisms play a role in this regulation, as well as other mechanisms such as transcription, phosphorylation, etc. Here, we investigated chromatin modifications in telomerase promoter upon exposure to ionizing radiation in human mesenchymal stem cells (hMSC) and telomerase-immortalized hMSCs (hMSC-telo1) together with a hMSC-telo1 cell line in which TRF2 expression was partially repressed (siTRF2 hMSC-telo1). Histone methylations and acetylations were compared in all cell lines after exposure to various doses of ionizing radiation (0.1, 1, 2.5 and 15 Gy) using chromatin immunoprecipitation assay. hTERT gene was shown to be quickly regulated through H3, H4 acetylations, as well as with H3K4 and H3K9 methylations, following radiation exposure, although the kinetic of hMSC-telo1 cells were different, indicative of the higher radioresistivity of these cells. To the author's surprise, there was an upregulation of endogenous telomerase activity in the hMSC-telo1 cells, even though the cells had already expressed high levels of ectopic hTERT. Our results show that telomerase regulation is one of the primary actions in response to damage and epigenetic factors play a major role in this regulation. Our results also suggested that partial silencing of TRF2 enhances the radiosensitivity of these cells, and endogenous telomerase is upregulated upon radiation, even under ectopic expression of hTERT in these cells.

An approach for cancer treatment is modulation of tumor microenvironment. Based on the role of extracellular matrix in cell modulation, fabrication of textured materials mimicking extracellular matrix could provide novel opportunities such as determining cancer cell behaviour. With this background, in this work, we have fabricated doxorubicin hydrochloride loaded nanotextured films which promote topographical attachment of cancer cells to film surface, and eliminate cells by release of the anti-cancer drug encapsulated within the films. These films are designed to be placed during surgical removal of the tumor with the intent to prevent ovarian cancer recurrence by capturing cancer cell residuals. With this aim, hemispherical protrusion shaped surface textures were acquired using colloidal lithography technique using 280 nm, 210 nm or 99 nm polystyrene particles. Once moulds were formed, nanotextured films were obtained by casting water-in-oil stable polycaprolactone emulsions encapsulating doxorubicin hydrochloride. Films were then characterized, and evaluated as drug delivery systems. According to results, we found that template morphologies were successfully transferred to films by atomic force microscopy studies. Hydrophilic surfaces were formed with contact angle values around 40 degrees.In-vitrodrug release studies indicated that nanotextured films best fit into the Higuchi model, and similar to 30% of the drug is released from the films within 60 days. Cell culture results indicated increases in the attachment and viability of human ovarian cancer cells to nanotextured surfaces, particularly to the film fabricated using 99 nm particles. Our results demonstrated that delivery of anti-cancer drugs by use of nanotextured materials could be efficient in cancer therapy, and may offer new possibilities for cancer treatment.

Telomere repeat binding factor TRF2 is a member of shelterin complex with an important role in protecting and stabilizing chromosomal ends. In the present study, we investigated the effect of partial knockdown of TRF2 on radiosensitivity of telomerase immortalized human mesenchymal stem cells (hMSC-telo1), which have a higher radioresistance compared to non telomerized counterpart. Partial knockdown of the protein achieved 15-20% reduction in TRF2 protein levels. The study compared the effect of 2.5Gy radiation in two-four days after irradiation for hMSC-telo1 cells and the cells transfected with siTRF2 and null control vector. Radio-response of the cells were examined using senescence associated β-Gal assay (β-Gal), colony forming assay (CFU) and γ-H2AX phosphorylation. TRF2 deficiency substantially increased radiosensitivity of cells compared to controls in both proliferation and senescence assay (2.4 fold increase in β-Gal, 1.6 fold decrease in CFU). In addition, it increased the γ-H2AX foci as revealed by both immunfluorescence and Western blot analysis. Our data suggests that partial knockdown of TRF2 in hMSC-telo1 cells cause increased γ-H2AX foci which led to fail TRF2 to protect telomeres from radiation thus TRF2 deficiency led to a 1,5-2 fold increase in the radiosensitivity of hMSC-telo1 cells through telomere destabilization.

The anticancer activity of Zingiber officinalis (ginger) is an area of active research. However, data is quite limited regarding its action and mechanism, especially in hematologic cancer types. Here, antiproliferative and apoptotic effects of whole extract of the rhizome of Zingiber officinalis (ZOWE), was investigated in K562 cell line derived from a chronic myeloid leukemia (CML) patient. Various concentrations of whole extract (0, 10, 25, 50 and 100 μM) were tested in K562 cultures. Cytotoxicity and apoptosis was assessed with appropriate methods, as well as cellular ROS levels. In this study, we showed that ZOWE inhibited proliferation of K562 cells substantially, when compared to peripheral blood mononuclear cells (PBMCs) isolated from healthy donor. Increased Bax/Bcl-2 ratio, reduced mitochondrial membrane potential and increased PARP cleavage demonstrated that ZOWE inhibited proliferation by induction of apoptosis. These changes were coupled with an increase of reactive oxygen species (ROS) production. Furthermore, ZOWE addition to the culture also reduced expression levels of survival proteins pAkt and survivin, in a concentration dependent manner. Our results clearly mark that ZOWE causes to a reduction in cell viability, an induction of apoptosis and elevation in ROS levels in chronic myeloid leukemia cells and effects are significantly different from healthy peripheral blood mononuclear cells, further supporting its potential therapeutic value.

Telomeres are the tandem repeats (TTAGGG) present at the ends of the chromosomes that ensure chromosome stability and protect chromosomes from degradation. Telomeres in somatic human cells shorten after every cellular division and are linked to the cellular senescence. In this study we have investigated telomere length and expression of shelterin genes in aborted fetus material from idiopathic recurrent pregnancy losses. Telomere length was measured using Telomere Restriction Fragment Length (TRF) analysis. The gene expression levels for important shelterin complex proteins (TRF1, TRF2, POT1, and TPP1) were determined by Real-time Quantitative Reverse Transcriptase PCR (qRT-PCR). Our results demonstrated down regulation of TRF2 and TPP1 and a strong decline in average telomere length in abort material from women suffering from idiopathic recurrent pregnancy loss. We suggest that shorter telomere length and downregulation of the major shelterin components TRF2 and TPP1 leading to "telomere uncapping", might play a critical role in recurrent pregnancy loss.

In this study, biological effects of High Intensity Focused Ultrasound (HIFU), which offer an effective treatment options for the treatment of solid tumors in recent years, will be determined on the colon cancer cell lines.

Pinar Mega Tiber,1 Latife Baloglu,2 Sevgi Ozden,3 Zerrin Ozgen,4 Hazan Ozyurt,3 Makbule Eren,3 Oya Orun11Department of Biophysics, Marmara University, School of Medicine, Maltepe, Istanbul, Turkey; 2Laboratory Medicine, Karolinska Institute Biomedical Laboratory Science, Stockholm, Sweden; 3Clinic of Radiation Oncology, Dr Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey; 4Department of Radiation Oncology, Marmara University, School of Medicine, Kaynarca, Istanbul, TurkeyObjective: To evaluate the expressions of several apoptotic pathway proteins in relation to clinical parameters and survival in patients with cervical carcinoma.Methods: A total of 20 patients with clinically advanced staged carcinoma of cervix (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) aged from 40 to 75 years were included in this study. The expression profile of anti-apoptotic protein (sensitive to apoptosis gene [SAG]), mitochondrial apoptotic proteins (B-cell lymphoma-extra-large [Bcl-xL] and Bcl-2 homologous antagonist/killer [Bak]), and tumor suppressor proteins (p73 and p53) were examined by real-time polymerase chain reaction experiments along with their relation to clinical parameters and survival analyses during follow-up for 5 to 8 years.Results: No significant difference was found in the expressions of SAG, Bcl-xL, Bak, p73 and p53 proteins with respect to stage and grade of tumor. A significant positive correlation was noted between SAG and Bcl-xL genes (r=0.752, P