An evaluation of DNA-damage response and cell-cycle pathways for breast cancer classification

Accurate subtyping or classification of breast cancer is important for ensuring proper treatment of patients and also for understanding the molecular mechanisms driving this disease. While there have been several gene signatures proposed in the literature to classify breast tumours, these signatures show very low overlaps, different classification performance, and not much relevance to the underlying biology of these tumours. Here we evaluate DNA-damage response (DDR) and cell cycle pathways, which are critical pathways implicated in a considerable proportion of breast tumours, for their usefulness and ability in breast tumour subtyping. We think that subtyping breast tumours based on these two pathways could lead to vital insights into molecular mechanisms driving these tumours. Here, we performed a systematic evaluation of DDR and cell-cycle pathways for subtyping of breast tumours into the five known intrinsic subtypes. Homologous Recombination (HR) pathway showed the best performance in subtyping breast tumours, indicating that HR genes are strongly involved in all breast tumours. Comparisons of pathway based signatures and two standard gene signatures supported the use of known pathways for breast tumour subtyping. Further, the evaluation of these standard gene signatures showed that breast tumour subtyping, prognosis and survival estimation are all closely related. Finally, we constructed an all-inclusive super-signature by combining (union of) all genes and performing a stringent feature selection, and found it to be reasonably accurate and robust in classification as well as prognostic value. Adopting DDR and cell cycle pathways for breast tumour subtyping achieved robust and accurate breast tumour subtyping, and constructing a super-signature which contains feature selected mix of genes from these molecular pathways as well as clinical aspects is valuable in clinical practice.Comment: 28 pages, 7 figures, 6 table

Comparison of gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients

Objectives: Uremic pruritus is a common problem in hemodialysis patients. Several treatments have been used for decreasing itching in these patients. Gabapentin and ketotifen are two drugs used for treating uremic patients.The aim of this study was to compare gabapentin and ketotifen in treatment of uremic pruritus in hemodialysis patients. Methods: In this double-blind randomized clinical trial, 52 hemodialysis patients with uremic pruritus referred to 5azarTeaching Hospital in Gorgan in 2013 were studied. Patients were randomly assigned to two groups of 26 subjects (groups G and K). In group G, patients treated with gabapentin capsules 100 mg daily for 2 weeks, and in Group K, patients treated with ketotifen 1 mg twice daily for 2 weeks. Before and at the end of study, pruritus severity was determined based on Shiratori›s severity scores. Collected data were analyzed by SPSS-21 statistical software. Results: There was no significant different between two groups in the age and sex. After two weeks of treatment, severity of pruritus was significantly reduced in both groups (88.4 in group G vs. 76.9 in group K). Gabapentin compared with ketotifen had a better effect on improving itching in the age group of 30-60 years and in males. 5 patients (19.2) in both groups suffered from drowsiness and dizziness, but no serious side effects were observed. Conclusions: The results showed that gabapentin and ketotifen significantly improved pruritus in hemodialysis patients, and no significant difference was observed between two groups. © 2016, Professional Medical Publications. All rights reserved

Wandering Spleen in an Adult Man Associated With the Horseshoe Kidney

Introduction: A wandering spleen occurs when there is a laxity of the ligaments that fix the spleen in its normal anatomical position. Case Presentation: This is a case report of a wandering spleen with horseshoe kidney in a 29-year-old male admitted with acute lower abdominal pain and vomiting to emergency department of Shariati hospital in Isfahan province. Sonographic examination showed a homogeneous 21 × 15 × 8 cm mass in the lower part of the abdomen and pelvis associated with a horseshoe kidney. Laparotomy confirmed the clinical and ultrasound findings. Conclusions: The association of horseshoe kidney with a wandering spleen in this case may be due to an embryological anomaly

Decreased expression of heat shock protein HSP90α after exposure to doxorubicin in breast cancer cell lines (MCF-7 and MDA-MB-231)

Background and purpose: Incidence of breast cancer is increasing day by day. Scientists are interested in the effects of inhibition of breast cancer cell on treatment of this cancer. The aim of this study was to determine IC50 of doxorubicin in 24 hours on cell lines MCF-7 and MDA-MB-231 and the expression of heat shock protein HSP90α as a factor in the cell before and after 24 hours exposure to doxorubicin in both breast cancer cell lines. Materials and methods: A descriptive interventional study was done in two cell lines MCF-7 and MDA-MB-231` after 24 hours exposure to doxorubicin. Sensitivity of cells to doxorubicin was determined using MTT Assay in excel software. HSP90α heat shock protein expression were qualitatively compared in both cell lines before and after exposure to doxorubicin using immunofluorescent techniques (Immunocytochemistry). Results: MTT Assay showed that IC50 value in MDA-MB-231 and MCF7 cells after 24 hours exposure to doxorubicin (the dose that kills 50% of cells) were 14.521 and 16.3315µM, respectively. Immunocytochemistry revealed that HSP90α protein expression in both cell lines after exposure to doxorubicin decreased compared to the control group. Conclusion: Cell density in cell lines (ER-) MDA-MB-231 and line MCF-7 (ER+) after exposure to doxorubicin and increasing the dose of medication, decreased indicating a dose dependent effect. Also, apoptosis occurred in both cell lines and expression of HSP90α decreased but MDA-MB-231 cells were found to be more sensitive. © 2017, Mazandaran University of Medical Sciences. All rights reserved

Laboratory study on inclined desalination discharges in perpendicular cross-flow

To mitigate the ecological impact of dense effluents discharged from diffusers, understanding the influence of ambient currents and discharge characteristics on desalination outfall performance is crucial. For this purpose, a series of laser-induced fluorescence (LIF) experimental tests were conducted to address the combined effects of the flowing current strength and nozzle inclination in the discharge region for dense jets issuing into a plane perpendicular to the cross-flows. Various nozzle discharge angles (30°, 45°, and 60°) and cross-flow Froude numbers (urF=[Formula presented]) are studied to assess 3D jet trajectory and concentration distribution. Empirical equations describing the dilution and geometrical characteristics of the jets are also derived. The findings indicate that deploying the 60° jet can achieve dilutions of over 50 % and 20 % compared to the 30° and 45° jets, respectively, due to its longer trajectory and greater expansion. Thus, the previously reported insensitivity of dilution to the nozzle angles in the range of 40°-70° for stationary ambient water is questioned herein when dealing with flowing currents. Moreover, the 60° jet is more sensitive to the changes in urF compared to the two other shallower angles. The presented outcomes provide valuable insights for safeguarding coastal water bodies through the efficient design of inclined dense outfall discharges

The combination of retinoic acid and estrogen can increase germ cells genes expression in mouse embryonic stem cells derived primordial germ cells

A B S T R A C T Generation of germ cells from embryonic stem cells in vitro could have great application for treating infertility. The temporal expression profile of several genes was expressed at different stages of germ cell development and examined in differentiation the mouse embryonic stem cells. Cells were treated in three groups of control, with 10−8M of all-trans retinoic acid and the combination of 10−9M of 17β-Estradiol and retinoic acid for 7, 12, 17 or 22 days. Quantitative RT-PCR and Immunofluorescent were used to investigate the possible inductive effects of estrogen on mouse embryonic stem cell-derived primordial germ cells. mRNA expression of Oct4 and Dazl were downregulated in embryonic stem cells by the retinoic acid group, whereas Mvh transcription was reduced by retinoic acid and estrogen group in these cells compared to the control group. But, retinoic acid with estrogen group-treated cells exhibited increased mRNA expression of Stra8, Fragilis, Sycp3, GDF9, and Stella compared to untreated controls. The expression of Stella and Mvh proteins were remarkably increased in cell colonies. This study shows that estrogen affects the expression of specific markers of primordial germ cells. Also, estrogen and retinoic acid speed up and increase the level of expression of specific markers. Keywords: Gene expression profiling Immunofluorescent Mouse embryonic stem cells Primordial germ cells RT PC

Amplification of superconducting fluctuations in driven YBa2Cu3O6+x

In cuprate high-Tc superconductors, resonant excitation of certain lattice vibrations has been shown to induce transient terahertz reflectivity features suggestive of nonequilibrium superconductivity above the critical temperature Tc. A microscopic mechanism for these observations is still lacking. Here, time-resolved measurements of scattering-angle- and polarization-dependent second-harmonic generation in driven YBa2Cu3O6+x reveal a three-order-of-magnitude amplification of a 2.5-THz electronic mode, which is unique because of its symmetry, momentum, and temperature dependence. A theory for amplification of finite-momentum Josephson plasma polaritons, which are assumed to be well formed below Tc but incoherent throughout the pseudogap phase, explains all these observations. A theoretical solution for the Fresnel-Floquet reflection that starts from the coherently oscillating Josephson plasma polaritons provides a possible mechanism for the nonequilibrium superconductorlike terahertz reflectivity reported earlier. Beyond the immediate case of cuprates, this work underscores the role of nonlinear mode mixing to amplify fluctuating modes above the transition temperature in a wide range of materials

False Positive Anti-Topoisomerase I (Scl-70) Antibody Results in Clinical Practice: A Case Series From a Scleroderma Referral Center

PURPOSE: To determine if some patients who tested positive for anti-Scl-70 antibody in clinical practice, but did not have classifiable systemic sclerosis, were negative for anti-Scl-70 antibody by the more specific immunodiffusion method of testing. METHODS: Patients evaluated by a rheumatologist at a Scleroderma referral center who had tested positive for anti-Scl-70 antibody prior to referral, but did not have classifiable SSc based on clinical criteria, were invited to undergo testing for anti-Scl-70 antibody by immunodiffusion. Patient demographics and clinical features were recorded at the time of their evaluation, and diagnostic testing results were reviewed using the medical records. RESULTS: 52 patients were enrolled over an 8-year period, with 48 (92.3%) testing negative and 4 (7.7%) testing positive for anti-Scl-70 antibody by immunodiffusion. Of the 48 patients who tested negative, 18 (37.5%) tested negative for ANA by indirect immunofluorescence, 33 (68.8%) did not have Raynaud\u27s phenomenon, and 43 (89.6%) had ≤1 clinical criteria items based on the 2013 ACR/EULAR SSc classification criteria. Nevertheless, 21 (43.8%) patients who were negative for anti-Scl-70 antibody by immunodiffusion had undergone a chest CT and 14 (29.2%) had undergone an echocardiogram. A total of 23 patients had at least one follow up clinic visit. 3 out of 4 patients who were positive for anti-Scl-70 antibody by immunodiffusion, but none of the 19 patients who tested negative by immunodiffusion, developed sufficient criteria during follow up to be classified as SSc. CONCLUSION: Assays for anti-Scl-70 antibody in commercial laboratories that are commonly utilized in clinical practice can produce false positive results. These results can lead to angst for patients, as well as unnecessary referrals and diagnostic evaluations

Experimental Study of Natural Convective Flow over a Hot Horizontal Rhombus Cylinder Immersed in Water via PIV Technique

Natural convective flow over a horizontal cylinder is a phenomenon used in many industries such as heat transfer from an electrical wire, heat exchanger, pipe heat transfer, etc. In this research, fluid dynamics of natural convective flow over a horizontal rhombus cylinder, with uniform heat flux, is investigated by using two-dimensional Particle Image Velocimetry (PIV) Technique. Experiments are carried out in a cubical tank full of water having an interface with air and the cylinder is placed horizontally inside the tank. The heater is turned on for 40s and the effects of heater's power and the height of water above the cylinder are surveyed. The experiments are carried out in three different heights of water and two different heater’s powers in which Rayleigh number changes from 1.33×107 to 1.76×107. The emitted heat flux causes the buoyancy force to be made and the main branch of flow to be formed. Then, moving up the main branch flow through the stationary water generates two equal anti-direction vortexes. These vortexes are developed when they reach the free surface. The results indicate that the flow pattern changes for different values of water height and heater’s power

Functionalization of Magnetic Nanoparticles by Folate as Potential MRI Contrast Agent for Breast Cancer Diagnostics

In recent years, the intrinsic magnetic properties of magnetic nanoparticles (MNPs) have made them one of the most promising candidates for magnetic resonance imaging (MRI). This study aims to evaluate the effect of different coating agents (with and without targeting agents) on the magnetic property of MNPs. In detail, iron oxide nanoparticles (IONPs) were prepared by the polyol method. The nanoparticles were then divided into two groups, one of which was coated with silica (SiO2) and hyperbranched polyglycerol (HPG) (SPION@SiO2@HPG); the other was covered by HPG alone (SPION@HPG). In the following section, folic acid (FA), as a targeting agent, was attached on the surface of nanoparticles. Physicochemical properties of nanostructures were characterized using Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and a vibrating sample magnetometer (VSM). TEM results showed that SPION@HPG was monodispersed with the average size of about 20 nm, while SPION@SiO2@HPG had a size of about 25 nm. Moreover, HPG coated nanoparticles had much lower magnetic saturation than the silica coated ones. The MR signal intensity of the nanostructures showed a relation between increasing the nanoparticle concentrations inside the MCF-7 cells and decreasing the signal related to the T2 relaxation time. The comparison of coating showed that SPION@SiO2@HPG (with/without a targeting agent) had significantly higher r2 value in comparison to Fe3O4@HPG. Based on the results of this study, the Fe3O4@SiO2@HPG-FA nanoparticles have shown the best magnetic properties, and can be considered promising contrast agents for magnetic resonance imaging applications. © 2020 by the authors. Licensee MDPI, Basel