The Possible Impact of Obesity on Androgen, Progesterone and Estrogen Receptors (ERα and ERβ) Gene Expression in Breast Cancer Patients

Background Obesity has been associated with increased mortality from hormone dependant cancers such as breast cancer which is the most prevalent cancer in women. The link between obesity and breast cancer can be attributed to excess estrogen produced through aromatization in adipose tissue. The role of steroid hormone receptors in breast cancer development is well studied but how obesity can affect the expression pattern of steroid hormones in patients with different grades of breast cancer was the aim of this study. Methods In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI < 25 kg/m 2 and 34 obese, BMI ≥ 25 kg/m 2 ). The mean age of participants was 44.53 ± 1.79 yr (21–70 yr). The serum level of estrogen, progesterone and androgen determined by ELISA. Following quantitative expression of steroid hormone receptors mRNA in tumor tissues evaluated by Real-time PCR. Patients with previous history of radiotherapy or chemotherapy were excluded. SPSS 16 was used for data analysis and P < 0.05 considered statistically significant. Results The difference in ERα, ERβ and PR mRNA level between normal and obese patients was significant ( P < 0.001). In addition, the expression of AR mRNA was found to be higher than other steroid receptors. There was no significant relation between ERβ gene expression in two groups ( P = 0.68). We observed a significant relationship between ERα and AR mRNA with tumor stage and tumor grade, respectively ( P = 0.023, P = 0.015). Conclusion According to the obtained results, it is speculated that obesity could paly a significant role in estrogen receptors gene expression and also could affect progression and proliferation of breast cancer cells

Hemodynamic effect of atrioventricular and interventricular dyssynchrony in patients with biventricular pacing: Implications for the pacemaker syndrome

Background/Objectives: Pacemaker syndrome was mainly described as the sequel of atrioventricular (AV) dyssynchrony. The role of interventricular (VV) dyssynchrony has not been studied yet. The aims of this study were to noninvasively assess the hemodynamic effects of different ventricular pacing sites with and without AV and VV dyssynchrony and to observe the patients for clinical symptoms of the pacemaker syndrome during the AV sequential and ventricular-only pacing modes. Materials and Methods: Between March 2009 and February 2010, 40 patients (28 men; mean age, 61 ± 15 years) with biventricular (BiV) device were enrolled. Mean systolic and diastolic blood pressures (BP) of 5 beats were measured 5 minutes after each mode change using fingertip plethysmography. The patients were also observed for the occurrence of symptoms suggestive of the pacemaker syndrome, including dyspnea, palpitations, dizziness, presyncope, and syncope. Results: There was no difference in mean systolic BP among different ventricular-only pacing modes (all P = NS). However, mean systolic BP was significantly higher in AV sequential biventricular pacing (DDD-BiV) compared with ventricular-only pacing modes (all P0.05). Conclusions: The present study showed that the non-AV sequential BiV and LV pacing may have no significant benefit compared with RV pacing in terms of systolic blood pressure. However, there was marked hemodynamic improvement following mode change to AV sequential BiV pacing. This study may have important implications for pathogenesis of pacemaker syndrome

Fabrication and characterization of cobalt- and copper-doped mesoporous borate bioactive glasses for potential applications in tissue engineering

Developing novel compositions of bioactive glasses (BGs) is key for accelerating tissue repair and regeneration. In this work, we developed a series of cobalt (Co)- and copper (Cu)-doped mesoporous bioactive glasses (MBGs) based on borate 13-93B3 composition using nitrate precursors. We took benefit from data science algorithms to predict and assess the physico-chemical and biological properties of the samples. The results showed that the presence of the dopants (Co and Cu) in the MBGs could change the glass transition temperature (Tg) (from 773 to 539 °C), the zeta potential (from -12 to -43 mV), and surface area (from 54 to 194 m2/g). However, the presence of 2.5 mol% of dopants in the composition led to just a slight decrease in their bioactivity. In vitro biocompatibility assays confirmed that all the glass samples were biocompatible. Furthermore, the doped MBGs exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In addition, these glasses could induce the mobility of human umbilical vein endothelial cells (HUVECs) and enhance new blood vessel formation in ovo. According to the obtained data, it can be stated that this type of doped borate MBGs held great promise in tissue engineering applications

Umbelliprenin-coated Fe3O4 magnetite nanoparticles: Antiproliferation evaluation on human Fibrosarcoma cell line (HT-1080)

The potential applications of Fe3O4 magnetite nanoparticles (MNPs) in nanomedicine as drug delivery systems are well known. In this study we prepared umbelliprenin-coated Fe3O4 MNPs and evaluated the antiproliferative effect of combination in vitro. After synthesis of Fe3O4 MNPs, particles were characterized by transmission electron microscopy, energy-dispersive spectroscopy, and X-ray diffraction spectroscopy techniques. The natural candidate compound — umbelliprenin— was isolated and identified and umbelliprenin-coated Fe3O4 MNPs were prepared, using precipitation method. The surface chemistry of umbelliprenin-coated Fe3O4 MNPs as well as their thermal decomposition characteristics was examined using Fourier transform infrared spectroscopy and Thermogravimetric Analyzer equipment, respectively. HT-1080 cells were cultured until the logarithmic phase of growth, and MTT assay was successfully carried out to evaluate the possible cytotoxic effects of umbelliprenin-coated Fe3O4 MNPs in viable cells in vitro. The results demonstrated that umbelliprenin has moderate antiproliferative effects with IC50 value of 50 μg/mL. However, the combination of umbelliprenin and Fe3O4 MNPs showed the IC50 value of 9 μg/mL. In other words, cell proliferation decreased to the remarkably-low proportion of 45% after treating cells with umbelliprenin-coated Fe3O4 MNPs. This suggests that with the aid of nanoparticles as carriers, natural products may have even broader range of medical applications in future

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Hand use predicts the structure of representations in sensorimotor cortex.

Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than by correlated muscle activity. This also generalized to an experiment using complex multi-finger movements. Finally, the organizational structure correlated with patterns of involuntary co-contracted finger movements for high-force presses. Together, our results suggest that hand use shapes the relative arrangement of finger-specific activity patterns in sensory-motor cortex

The combination effects of trivalent gold ions and gold nanoparticles with different antibiotics against resistant Pseudomonas aeruginosa

Despite much success in drug design and development, Pseudomonas aeruginosa is still considered as one of the most problematic bacteria due to its ability to develop mutational resistance against a variety of antibiotics. In search for new strategies to enhance antibacterial activity of antibiotics, in this work, the combination effect of gold materials including trivalent gold ions (Au ) and gold nanoparticles (Au NPs) with 14 different antibiotics was investigated against the clinical isolates of P. aeruginosa, Staphylococcus aureus and Escherichia coli. Disk diffusion assay was carried out, and test strains were treated with the sub-inhibitory contents of gold nanomaterial. Results showed that Au NPs did not increase the antibacterial effect of antibiotics at tested concentration (40 μg/disc). However, the susceptibility of resistant P. aeruginosa increased in the presence of Au and methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid, up to 147 %. As an individual experiment, the same group of antibiotics was tested for their activity against clinical isolates of S. aureus, E. coli and a different resistant strain of P. aeruginosa in the presence of sub-inhibitory contents of Au , where Au increased the susceptibility of test strains to methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid. Our finding suggested that using the combination of sub-inhibitory concentrations of Au and methicillin, erythromycin, nalidixic acid or vancomycin may be a promising new strategy for the treatment of highly resistant P. aeruginosa infections