ABSTRACT This study is focused on discrete subaortic stenosis (DSS) which is a congenital heart disease resulting in the formation of fibrotic tissue in the left ventricular outflow track of pediatric patients [1]. The pathogenesis of the molecular mechanism resulting in the formation of the fibrotic tissue remains unknown and is the focus of this study. We hypothesized the cytokine released in response to wall shear stress act on the fibroblasts to promote the formation of the fibrotic membrane and subsequently, DSS. To test this study hypothesis, porcine endocardial endothelial cells were cultured within cone and plate bioreactors, designed to replicate the wall shear stress observed in the left ventricular outflow track of DSS patients. Conditioned media was collected as a function of shear stress magnitude and used to condition porcine cardiac fibroblasts. We used an extensive set of end-point metrics to characterize fibroblast phenotype to include bulk-RNA sequencing, RT-qPCR, cell viability and immunofluorescence. The results of this study demonstrate that shear stress-conditioned media from porcine EEC releases a defined cocktail of cytokines that provide the trigger to program the fibrotic response during DSS. These results provide specific molecular targets that can be developed into a therapeutic strategy for patients with DSS and provide a solution to an otherwise challenging disease to manage.

This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation stands as the optimal option, yet the scarcity of organs persists. Employing tissue engineering, researchers sought to assess the feasibility of generating kidneys for transplantation. Pig kidneys were utilized since they possess higher similarities to human kidneys. Cells were removed via decellularization, which maintains the organ's microarchitecture. Subsequently, pig kidney cells and human red blood cells were perfused into the vacant kidney structure to reconstitute it. The methodologies employed showed promising results, suggesting a viable approach to increase the recellularization rate in whole pig kidneys. This proof-of-concept establishes a groundwork for potentially extending this technology to human kidneys, tackling the organ shortage, thus positively enhancing outcomes for ESRD patients by increasing the availability of transplantable organs.
© 2024. The Author(s).

Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy.
© 2024 The Authors.

This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation is the best option, but there aren't enough organs available. The researchers used tissue engineering to evaluate the possibility for creating kidneys for transplantation. They used pig kidneys, removing cells through a process called decellularization while preserving the organ's microarchitecture. The researchers then perfused pig kidney cells and human red blood cells to the empty kidney structure to recreate it. The methodologies used, showed promising results, suggesting a hopeful method to address the organ shortage. This proof-of-concept lays the foundation for potentially applying this technology to human kidneys, which could significantly improve outcomes for ESRD patients by providing more transplantable organs.

Growing evidence indicates that the epithelial to mesenchymal (E/M) hybrid state plays a key role in tumorigenesis. Importantly, a hybrid mesenchymal to epithelial transition (MET) state in which individual cells express both epithelial and mesenchymal markers was recently identified in vivo, further strengthening the bonds between the hybrid EMT state and cancer progression. However, the role and the molecular mechanisms by which the hybrid MET state is maintained in triple-negative breast cancer cells (TNBC) remain elusive. Here, we find that loss of ZHX2 expression results in the hybrid MET phenotype in mesenchymal TNBC cells. Mechanistically, through directly binding to the CDH1 promoter, depletion of ZHX2 specifically reactivates expression of CDH1 encoding E-cadherin, an epithelial marker that is crucial for maintaining epithelial phenotype. Functionally, loss of ZHX2 expression enriches the hybrid MET cells and inhibits the migration and dissemination of TNBC cells or organoids, which could be reversed by restoration of E-cadherin. Moreover, depletion of ZHX2 suppresses lung metastasis in preclinical models of TNBC. In patients with TNBC, ZHX2 expression was amplified and negatively correlated with the expression of E-cadherin. These findings suggest that loss of ZHX2 promotes the hybrid MET state to impair TNBC progression.
© 2023. The Author(s).