Chromosome conformation capture-based DNA hybridization method for chromosomal translocation screening.

Background: DNA probes have been widely used as diagnostic tools for translocations. This study sought to design a screening tool using ssDNA probes and chromosome conformation capture (3C) library fragment hybridization. Method: The authors focused on developing a probe for the juxtaposed region of MYC and TRD. Fragments of the MYC gene with a thiol modification (MYC-Au NP probe) were functionalized by gold nanoparticles (Au NPs). Then TRD probes were immobilized on a nitrocellulose surface. Hybridization between DNA probes and 3C library fragments of SKW3 cells was determined by color intensity. Results: Optimal hybridization of the 3C library sample of the cell line to probes showed higher color intensity than human umbilical vein endothelial cells. Conclusion: Combining 3C-based techniques and DNA-DNA hybridization can identify rearrangements in cancer cells.

Anti-angiogenic effects of testis-specific gene antigen 10 on primary endothelial cells.

Growing evidence indicates the antitumor and antiangiogenesis activities of testis-specific gene antigen 10 (TSGA10). However, the underlying mechanisms and precise role of TSGA10 in angiogenesis are still elusive. In this study, we isolated human umbilical cord vein endothelial cells (HUVECs) and stably transfected with pcDNA3.1 carrying TSGA10 coding sequence. We demonstrated that TSGA10 over-expression significantly decreases HUVEC tubulogenesis and interconnected capillary network formation. HUVECs over-expressing TSGA10 exhibited a significant decrease in migration and proliferation rates. TSGA10 over-expression markedly decreased expression of angiogenesis-related genes, including VEGF-A, VEGFR-2, Ang-1, Ang-2, and Tie-2. Our ELISA results showed the decrease in VEGF-A mRNA expression level is associated with a significant decrease in its protein secretion. Additionally, over-expressing TSGA10 decreased expression levels of marker genes of cell migration (MMP-2, MMP-9, and SDF-1a) and proliferation (PCNA and Ki-67. Furthermore, ERK-1 and AKT phosphorylation significantly reduced in HUVECs over-expressing TSGA10. Our findings suggest a potent anti-angiogenesis activity of TSGA10 in HUVECs through down-regulation of ERK and AKT signalling pathways, and may provide therapeutic benefits for the management of different pathological angiogenesis.

Cell Free Tumoral DNA Versus Paraffin Block Epidermal Growth Factor Receptor Mutation Detection in Patients with Non-Small Cell Lung Cancer.

Increasing knowledge about the molecular profile of tumors has led to personalized treatment for achieving better outcomes in patients with nonsmall cell lung cancer (NSCLC). Currently, finding exact somatic genomic changes of tumor has gained great importance. On the other hand, crescendoing needs to actual tumor tissue at different time points during cancer treatment may produce major discomfort for NSCLC patients. Tumor genomes can be reconstructed by information obtained from circulating cell-free deoxyribonucleic acid (cfDNA) of peripheral blood. cfDNA may be represented as a suitable alternative test  for epidermal growth factor receptor (EGFR) mutation detection in these patients. This study aimed to assess validity of cfDNA in somatic EGFR mutation identification in Iranian NSCLC cases. METHODS: Somatic mutation of EGFR gene was studied in both tissue specimens and plasma. Then, mutations were detected by polymerase chain reaction(PCR) and sequencing. RESULTS: We observed a high concordance (90%) between tissue samples and cfDNA for EGFR gene mutation.  The sensitivity, accuracy, and positive precision value were 90%, 90% and 100%, respectively. A false negative rate of 10% was also demonstrated in this study. CONCLUSION: We established sensitive methods for detecting EGFR gene mutation which may be very useful in clinical practice.
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Coexistence of Anticoagulant and Anti-vascular Calcification Activities in Kribbella sp. UTMC 267 Metabolites.

Thrombotic disorders increase the risk of cardiovascular/cerebrovascular complications and represent a major health problem worldwide. Anticoagulants are extensively used in treatment of these disorders. Vitamin K antagonists, like Warfarin, are frequently used in medication. Vascular calcification (VC) is a significant side-effect of vitamin K antagonists especially Warfarin. There is an urgent need to find natural, efficient, non-toxic, and cost effective anticoagulants without dangerous side-effect like VC. In the present study, we evaluated the potential of thirteen fermentation broth extracts of actinobacteria (FBEA) (200 µg mL-1) to prolong whole blood prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (APTT). The fractions of the most effective FBEA were further investigated for their inhibitory effect on VC. The results showed PT/INR of the healthy blood samples was sensitive to the presence of five FBEA. Their INR index fell in the 1.2 to 8.6 range and six FBEA prolonged both PT/INR and APTT parameters (1.7-5 INR, and 46-59 s for APTT). The fractions of Kribbella sp. UTMC 267 FBE (200 µg mL-1), as the most efficient FBE, only inhibited intrinsic and common pathways of coagulation (APTT). Under calcification condition, Kribbella sp. UTMC 267 fractions (20 µg mL-1) showed significant inhibitory effect on VC in alizarin red staining (13.3-76 %) and alkaline phosphatase activity of VSMCs (33-62%). They also inhibited osteopontin mRNA expression in treated vascular smooth muscle cells (VSMCs) under that situation. So, we can introduce Kribbella sp. UTMC 267 FBE as a good candidate for more investigation on thrombotic medication.

Performance and Predictive Value of First Trimester Screening Markers for Down Syndrome in Iranian Pregnancies.

Objective: To investigate the performance of first trimester Down syndrome (DS) screening markers in Iranian pregnancies.Although sonographic and serum markers are currently recommended for the first trimester screening of Down syndrome, the screening performance of the markers depends on the race and ethnicity. Materials and methods: A retrospective case-control study using first trimester screening results recorded with the prenatal diagnostic multi-centers in Iran. A total of 6,384 pregnant women were examined from March 2012 to February 2017. Totally 100 Down syndrome cases and 266 matched controls were selected and the maternal characteristics, sonographic and biochemical screening data were collected. Statistical analysis was performed using logistic regression and descriptive statistics. A decision tree model was designed using the chi-squared automatic interaction detection method based on serum markers. Results: For screening of DS pregnancies, PAPP-A (cut-off 0.795 MoM) yielded the highest sensitivity (86%) and NB marker presented highest specificity (96.24%). combination of the biochemical markers PAPP-A and ß-hCG (cut-off: 1.55 MoM) showed the highest sensitivity over other combined markers. The decision-tree model based on serum markers improved (91% DR For a 5% FPR) first trimester screening performance. Conclusion: The novel decision-tree model base on serum markers revealed a better predictive value to achieve high sensitivity and specificity of first trimester Down syndrome screening in Iranian population.

Collagen Extracted from Persian Gulf Squid Exhibits Anti-Cytotoxic Properties on Apple Pectic Treated Cells: Assessment in an In Vitro Bioassay Model.

BACKGROUND: Collagen-based three-dimensional (3D) in vitro systems have been introduced to study the physiological states of cells. As a biomolecule, collagen is usually extracted from terrestrial animals whilst aquatic animals like squid contain large amounts of collagen. METHODS: In order to make effective use of marine organisms, we selected Persian Gulf squid in 2015 to extract the required collagen. Then, a 3D culture system based on the extracted collagen was applied to investigate cellular mechanisms in a native microenvironment. The formed collagen gel was used to investigate the growth of MDA-MB-231 breast cancer cells as well as responses to pectic acid. RESULTS: The results revealed that the extracted collagen contained α, ß and γ components with high water holding capacity. This collagen formed a gel-like structure, which could promote the proliferation of MDA-MB-231 breast cancer cells. The MDA-MB-231 cells' viability in presence of pectic acid, demonstrating the cells' behavior in a 3D culture system. CONCLUSION: It seems that the collagen extracted from squid skin has type I collagen properties. It might be used as a substrate in 3D cell culture systems.

Strengthening medical ethics by strategic planning in the Islamic Republic of Iran.

To bring attention to medical ethics and to enhance the quality of health care in Iran, the Ministry of Health and Medical Education has introduced a strategic plan for medical ethics at a national level. This plan was developed through the organization and running of workshops in which experts addressed important areas related to medical ethics. They analysed strengths and weaknesses, opportunities and threats, and outlined a vision, a mission and specific goals and essential activities surrounding medical ethics. The current strategic plan has six main goals that will be reviewed in this paper. Some major activities that were carried out in recent years, and some future plans, will be also reviewed.