Single nucleus RNA-sequencing reveals altered intercellular communication and dendritic cell activation in nonobstructive hypertrophic cardiomyopathy

End stage, nonobstructive hypertrophic cardiomyopathy (HCM) is an intractable condition with no disease-specific therapies. To gain insights into the pathogenesis of nonobstructive HCM, we performed single nucleus RNA-sequencing (snRNA-seq) on human HCM hearts explanted at the time of cardiac transplantation and organ donor hearts serving as controls. Differential gene expression analysis revealed 64 differentially expressed genes linked to specific cell types and molecular functions. Analysis of ligand-receptor pair gene expression to delineate potential intercellular communication revealed significant reductions in expressed ligand-receptor pairs affecting the extracellular matrix, growth factor binding, peptidase regulator activity, platelet-derived growth factor binding and protease binding in the HCM tissue. Changes in Integrin-beta1 receptor expression were responsible for many changes related to extracellular matrix interactions, by increasing in dendritic, smooth muscle and pericyte cells while decreasing in endothelial and fibroblast cells, suggesting potential mechanisms for fibrosis and microvascular disease in HCM and a potential role for dendritic cells. In contrast, there was an increase in ligand-receptor pair expression associated with adenylate cyclase binding, calcium channel molecular functions, channel inhibitor activity, ion channel inhibitor activity, phosphatase activator activity, protein kinase activator activity and titin binding, suggesting important shifts in various signaling cascades in nonobstructive, end stage HCM.

Perspectives on PARP Inhibitor Combinations for Ovarian Cancer

Poly (ADP-ribose) polymerase (PARP) inhibitors constitute an important treatment option for ovarian cancer nowadays. The magnitude of benefit from PARP inhibitors is influenced by the homologous recombination status, with greater benefit observed in patients with BRCA mutated or BRCA wild-type homologous recombination deficient (HRD) tumors. Although some PARP inhibitor activity has been shown in homologous recombination proficient (HRP) ovarian tumors, its clinical relevance as a single agent is unsatisfactory in this population. Furthermore, even HRD tumors present primary or secondary resistance to PARP inhibitors. Strategies to overcome treatment resistance, as well as to enhance PARP inhibitors’ efficacy in HRP tumors, are highly warranted. Diverse combinations are being studied with this aim, including combinations with antiangiogenics, immunotherapy, and other targeted therapies. This review discusses the rationale for developing therapy combinations with PARP inhibitors, the current knowledge, and the future perspectives on this issue.

Effect of traditional processing methods on protein digestibility and chemical constituents in seeds of Bauhinia petersiana

Background: Antinutritional factors present in food may reduce the bioavailability of nutrients and cause harmful effects to human health. Aims: The aim of this study was to determine the effect of traditional processing methods on protein digestibility, nutrient and antinutrient constituents of seeds of Bauhinia petersiana. Subjects and Methods: The seeds were processed by soaking in water, boiling or roasting before analyzing protein digestibility, nutrient and antinutrient compositions. Results: Soaking resulted in no significant changes in the content of moisture, protein, fiber, phytates and trypsin inhibitor activity and significant reductions in fat, ash and tannins. Roasting resulted in no significant change in the content of moisture, ash, protein, and fiber and significant reductions in fat, phytates and trypsin inhibitor activity. Boiling resulted in a significant increase in the content of both protein and fiber and reduction in fat, ash, tannins, phytates and trypsin inhibitor activity. Mineral content of zinc, magnesium and calcium was not changed by soaking, roasting or boiling of the seeds. The calculated phytate: zinc molar ratios for both the raw and processed seeds were greater than 10, the limit for optimal absorption of zinc in the small intestine whereas phytate: iron molar ratios were less than 14, the limit for optimum absorption of iron in the intestines. In vitro digestibility of proteins in the seeds was increased when the seeds were soaked, roasted or boiled. Conclusions: Boiling the seeds of B. petersiana before consumption would effectively remove undesirable antinutrients while maintaining the nutrient content of the seeds and improving digestibility of proteins. Keywords: Legume, nutrient, antinutrient, digestibility, phytate.