This work was supported by NIH R01 HD067721 (to S.L.Y and B.A.L) and NIH R01 HD057873 and American Cancer Society Research Grant RSG-12-084-01-TBG (to J.-W.J.). There are no conflicts of interest.
Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4 resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of STAT3 and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4 responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells and the anti-tumor effects of P4 are mediated by the endometrial stroma. This data helps to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer.
Cardiac cell therapy has the potential to revolutionize treatment of heart diseases, but its success hinders on the development of a stem cell therapy capable of efficiently producing functionally differentiated cardiomyocytes. A key to unlocking the therapeutic application of stem cells lies in understanding the molecular mechanisms that govern the differentiation process. Here we report that a population of platelet-derived growth factor receptor alpha (PDGFRA) cells derived from mouse multipotent germline stem cells (mGSCs) were capable of undergoing cardiomyogenesis in vitro. Cells derived in vitro from PDGFRA positive mGSCs express significantly higher levels of cardiac marker proteins compared to PDGFRA negative mGSCs. Using Pdgfra shRNAs to investigate the dependence of Pdgfra on cardiomyocyte differentiation, we observed that Pdgfra silencing inhibited cardiac differentiation. In a rat myocardial infarction (MI) model, transplantation of a PDGFRAenriched cell population into the rat heart readily underwent functional differentiation into cardiomyocytes and reduced areas of fibrosis associated with MI injury. Together, these results suggest that mGSCs may provide a unique source of cardiac stem/progenitor cells for future regenerative therapy of damaged heart tissue.
One of the best ways to monitor the health of the heart is to regularly record its electrical activity by using an electrocardiogram (ECG). Abnormal ECG signals may indicate conditions such as heart attack, arrhythmia, or heart defects. There are many ECG devices available which can detect and amplify this differential biological signal from the heart, allowing a lot of information to be collected quickly. The ECG is often small and easy to use, but its power is supplied from regular batteries, which need to be replaced after a certain period of use. This causes discomfort for elderly users. To overcome this limitation, in this paper, we aim to develop a solar-powered, portable Bluetooth device for ECG measurements. The device can be interfaced with smartphones or other wireless devices via Bluetooth by a distance up to 100 m. The ECG device was designed to use solar energy, which is also the main power source. Following the solar energy harvesting circuit is a solar panel with an output voltage of 2.4 V and a power out of 0.25 W. We optimized the design to have a very low power consumption and in sleep mode the current consumption is only around 40 µA. The device was designed with 24-bit resolution and a sampling frequency of up to 2133 Hz, which can allow high accuracy ECG measurements. The device is not only used for heart rate monitoring, but it can also assist doctors in analyzing ECG signals with a high accuracy via embedded operating software.
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