Hypertrophic cardiomyopathy-associated mutations drive stromal activation via EGFR-mediated paracrine signaling.

Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the left ventricular wall, diastolic dysfunction, and fibrosis, and is associated with mutations in genes encoding sarcomere proteins. While in vitro studies have used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study HCM, these models have not examined the multicellular interactions involved in fibrosis. Using engineered cardiac microtissues (CMTs) composed of HCM-causing MYH7-variant hiPSC-CMs and wild-type fibroblasts, we observed cell-cell cross-talk leading to increased collagen deposition, tissue stiffening, and decreased contractility dependent on fibroblast proliferation. hiPSC-CM conditioned media and single-nucleus RNA sequencing data suggested that fibroblast proliferation is mediated by paracrine signals from MYH7-variant cardiomyocytes. Furthermore, inhibiting epidermal growth factor receptor tyrosine kinase with erlotinib hydrochloride attenuated stromal activation. Last, HCM-causing MYBPC3-variant CMTs also demonstrated increased stromal activation and reduced contractility, but with distinct characteristics. Together, these findings establish a paracrine-mediated cross-talk potentially responsible for fibrotic changes observed in HCM.

First Presentation and Diagnosis of a Rare Advanced Gynaecological Cancer in Emergency Department: A Case Report.

A case of rare endometrial carcinosarcoma with locoregional spread and sigmoid fistula presenting for the very first time at a hospital emergency department (ED). A 56-year-old female presented with abdominal pain, diarrhea, fever, and pancytopenia, which was diagnosed as advanced gynaecological cancer following assessment, imaging, and tissue biopsy. Increased pressure on the ED owing to coronavirus disease 2019 pandemic may cause the first presentation of gynae-oncology cases to ED physician. A full return of all primary care services may reduce such pressure, improve early detection of gynaecological malignancies, allow early multidisciplinary team care, and result in better patient experience in the long run.

Identification of Genes and Pathways Involved in Ovarian Epithelial Cancer by Bioinformatics Analysis.

Ovarian epithelial cancer (OEC) is an often fatal disease with poor prognosis in women with high-stage disease. In contrast, ovarian low malignant potential (LMP) tumors with favorable prognosis behaves as a disease between benign and malignant tumors. The involved genes and pathways between benign-like LMP and aggressive OEC are largely unknown. This study integrated two cohorts profile datasets to investigate the potential key candidate genes and pathways associated with OEC. Gene expression in two datasets (GSE9891 and GSE12172), including 327 OECs and 48 LMP tumors, were analyzed. 559 differentially expressed genes were found to overlap, 251 up-regulated and 308 down-regulated. Subsequently, analysis of gene ontology, signaling pathway enrichment and protein-protein interaction (PPI) network was performed. Gene ontology analysis clustered the up-regulated and down-regulated genes based on significant enrichment. 282 nodes/ differentially expressed genes (DEGs) were identified from DEGs PPI network complex, and two most significant k-clique modules were identified from PPI. In a summary, using integrated bioinformatics analysis, we are able to identify biomarkers potentially significant in the pathogenesis of OEC, which can improve our understanding of the cause and molecular events. These candidate genes and pathways could be used for further confirmation, and lead to better disease diagnose and therapy.