Cardiomyocyte-specific estrogen receptor alpha increases angiogenesis, lymphangiogenesis and reduces fibrosis in the female mouse heart post-myocardial infarction

Experimental studies showed that 17{beta}-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER{alpha} in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ER-{alpha} (ER{alpha}-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ER{alpha}-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ER{alpha}-OE, but not in female ER{alpha}-OE mice. ER{alpha}-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ER{alpha}-OE after MI. In conclusion, our study indicates that ER{alpha} protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient's body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons. © 2021 The Author

Critical Grain Size of Fine Aggregates in the View of the Rheology of Mortar

The aim of this research was to investigate the validity of the Krieger-Dougherty model as a quantitative model to predict the viscosity of mortar depending on various aggregate sizes. The Krieger-Dougherty model reportedly predicted the viscosity of a suspension, which includes cement-based materials. Concrete or mortar incorporates natural resources, such as sand and gravel, referred to as aggregates, which can make up as much as 80% of the mixture by volume. Cement paste is a suspending medium at fresh state and then becomes a binder to link the aggregate after its hydration. Both the viscosity of the suspending medium and the characteristics of the aggregates, therefore, control the viscosity of the cement-based materials. In this research, various sizes and gradations of fine aggregate samples were prepared. Workability and rheological properties were measured using fresh-state mortar samples and incorporating the various-sized fine aggregates. Yield stress and viscosity measurements were obtained by using a rheometer. Based on the packing density of each fine aggregate sample, the viscosity of the mortar was predicted with the Krieger-Dougherty model. In addition, further adjustments were made to determine the water absorption of fine aggregates and was transferred from successful experiment to simulation for more accurate prediction. It was also determined that both yield stress and viscosity increase when the fine aggregate mean size decreases throughout the mix. However, when the mean size of the fine aggregates is bigger than 0.7 mm, the yield stress is not affected by the size of the fine aggregate. Additionally, if aggregate grains get smaller up to 0.3 mm, their water absorption is critical to the rheological behavior

Sex-specific pathways in early cardiac response to pressure overload in mice

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF

Compact Self-Isolated Four-Element MIMO Antenna for WLAN and ISM Bands Application

A compact self-isolated four-element MIMO antenna is introduced for use in ISM systems and WLAN applications in the 2.4 GHz frequency band. The proposed design consists of four printed dipoles so four integrated baluns are responsible for feeding these antennas. By choosing an appropriate arrangement of the elements next to each other and using the feature of self-isolated antennas, great isolation is achieved in the first step. Finally, by utilizing a printed decoupling component in the space between the dipoles, the value of the envelope correlation coefficient (ECC) parameter comes very close to zero for the MIMO antenna. The major part of the isolation in this design is the responsibility of the self-isolated technique, and adding the decoupling element at the last stage of the design is to complete the antenna isolation process. The fabricated prototype of the proposed MIMO antenna operating at 2.25-2.87 GHz frequency band reaches the measured port-to-port isolation of better than 19 dB, ECC of less than 0.0009, the peak gain of 8.6 dBi with total dimensions of $1.11\lambda _{0}\times 1.11 \lambda _{0}\times 0.34\lambda _{0}$ . The numerical and experimental results approve the excellent MIMO performance for 2.4 GHz applications

Recommendations for breast surgical care during COVID-19 outbreak in Iran: setting priorities of management

Objective: During the recent pandemic of COVID-19, apposite planning is necessary to maintain health system resources. Cancer patients are susceptible to COVID-19, but accurate cancer management should be carried out.  As breast cancer is the most common female cancer in Iran, and surgery is the main treatment, we carried out this study to provide the best recommendations for breast surgery and care during the outbreak of COVID-19 in Iran. Materials and Methods: As cancer and breast surgeons at Cancer Institute of Iran, based on our personal and institutional experience and recently released guidelines, we defined the main headings about breast surgery issues during the outbreak. We investigated the present literature and then discussed each issue. Results: The best agreed recommendations were delineated. Briefly, telemedicine should be prioritized over in-hospital presence of patients. Visits should be postponed except for cancer workups and treatments, or cases suspicious for cancer. Appropriate protective, preventive, and instructive measures related to COVID-19 should be observed in the outpatient and inpatient Departments for patients, companions, and health care providers. Staging procedures should be minimized. Surgery for non-malignant lesions, reconstructive and cosmetic surgery should be postponed. When breast cancer surgery can be substituted by non-operative treatments without impairing prognosis or quality of life, it should be deferred. Surgeries with lower complication rates and length of stay are favored. Conclusions: At the time of COVID-19 epidemic, surgery should be performed for breast cancer only if this modality is more advantageous than other therapies in terms of disease outcome and is worth the increased risk of transmission of COVID-19. Otherwise, it should be deferred until control of the epidemic

Management policies of breast cancer surgery, chemotherapy and radiotherapy during COVID-19 outbreak in Iran

Objective: Introducing a modified guideline to save medical and human resources during COVID-19, and suggesting modifications to cancer treatment procedures during COVID-19 with the aim of reducing patients’ exposures to medical centers. Materials and Methods: Breast cancer management protocols were discussed among our colleagues in Cancer Institute of Tehran University of Medical Sciences through interactive applications (WhatsApp and Skype). We have provided the consensus of all opinions under relevant headings. Our recommendations will be modified as pandemic severity changes. Results: Surgery is restricted to patients whose survival is likely to be compromised if surgery is not performed. As for systemic therapy, we prefer to prescribe less toxic regimens and choose tri-weekly cycles instead of bi-weekly or weekly ones. In the case of radiotherapy, hypofractionated schedules are preferred schedules. Conclusions: COVID-19 pandemic put cancer patients, physicians, and health care systems in a challenging situation. All our colleagues agreed to choose less invasive and minimal interventions at this time because it is imperative to spare medical resources and workforce, and decrease patients’ contact with medical environments. We know that some of our suggestions may interfere with standard and routine practice, but our recommendations will be changed when COVID-19 pandemic severity changes