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

CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70�75. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80�98, but similar accuracy of 70. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95 compared to radiologists (70). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership. © 2021, The Author(s)

Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: involvement of circadian clock genes

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most prevalent joint diseases. A such, they are important causes of pain and disability in a substantial proportion of the human population. A common characteristic of these diseases is the erosion of articular cartilage and consequently joint dysfunction. Melatonin has been proposed as a link between circadian rhythms and joint diseases including RA and OA. This hormone exerts a diversity of regulatory actions through binding to specific receptors and intracellular targets as well as having receptor-independent actions as a free radical scavenger. Cytoprotective effects of melatonin involve a myriad of prominent receptor-mediated pathways/molecules associated with inflammation, of which the role of omnipresent NF-κB signalling is crucial. Likewise, disturbance of circadian timekeeping is closely involved in the aetiology of inflammatory arthritis. Melatonin is shown to stimulate cartilage destruction/regeneration through direct/indirect modulation of the expression of the main circadian clock genes, such as BMAL, CRY and/or DEC2. In the current article, we review the effects of melatonin on RA and OA, focusing on its ability to regulate inflammatory pathways and circadian rhythms. We also review the possible protective effects of melatonin on RA and OA pathogenesis. Linked Articles: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc. © 2017 The British Pharmacological Societ

Multifunctional nanostructures : Intelligent design to overcome biological barriers

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and phar-macokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is inti-mately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.Peer reviewe