ZEB1 truncating mutations result in a significant decrease and/or impaired nuclear localization of the encoded protein, indicating that ZEB1 haploinsufficiency in PPCD3 may result from decreased protein production and/or impaired cellular localization. Conversely, as the reported ZEB1 missense mutations do not significantly impact protein abundance or nuclear localization, the effect of these mutations on ZEB1 function and their relationship to FECD, if any, remain to be elucidated.

Posterior polymorphous corneal dystrophy (PPCD) is a dominantly inherited disorder of the corneal endothelium that has been associated with mutations in the zinc-finger E-box binding homeobox 1 gene (ZEB1) gene in approximately one-third of affected families. While the corneal dystrophies have traditionally been considered isolated disorders of the corneal endothelium, we have recently identified two cases of maldevelopment of the corpus callosum in unrelated individuals with PPCD. The proband of the first family was diagnosed shortly after birth with agenesis of the corpus callosum and several other developmental abnormalities. Karyotype, FISH and whole genome copy number variant analyses were normal. She was subsequently diagnosed with PPCD, prompting screening of the ZEB1 gene, which identified a novel deletion (c.449delG; p.(Gly150Alafs*36)) present in the heterozygous state that was not identified in either unaffected parent. The proband of the second family was diagnosed several months after birth with thinning of the corpus callosum and PPCD. Whole genome copy number variant analysis revealed a 1.79 Mb duplication of 17q12 in the proband and her father and brother, neither of whom had PPCD. ZEB1 sequencing identified a novel deletion (c.1913-1914delCA; p.(Ser638Cysfs*5)) present in the heterozygous state, which was also identified in the proband’s affected mother. Thus, we report the first two cases of the association of PPCD with a developmental abnormality of the brain, in this case maldevelopment of the corpus callosum. Keywords: agenesis, corpus callosum, PPCD3, ZEB1, ZEB2, corneal dystrophy

There is increasing evidence that matrix stiffness modulates various phenotypic activities of cells surrounded by a three-dimensional (3D) matrix. These findings suggest that matrix stiffness can also regulate dermal fibroblasts activities to remodel, repair, and recreate skin dermis, but this has not yet been systematically demonstrated to date. This study examines the effects of matrix rigidity on the morphology, growth rates, and glycosaminoglycan (GAG) production of dermal fibroblasts cultured in collagen-based hydrogels with controlled elastic moduli. The elastic moduli (E) of collagen hydrogels were increased from 0.7 to 1.6 and 2.2  kPa by chemically cross-linking collagen fibrils with poly(ethylene glycol) disuccinimidylester. Increasing E of the hydrogel led to decreases in cellular spreading, nuclear aspect ratio, and growth rate. In contrast, the cellular GAG production level was elevated by increasing E from 0.7 to 1.6  kPa. The larger accumulation of GAG in the stiffer hydrogel led to increased water retention during exposure to air, as confirmed with magnetic resonance imaging. Additionally, in a chicken chorioallantoic membrane, a cell-encapsulating hydrogel with E of 1.6  kPa created dermis-like tissue with larger amount of GAG and density of blood vessels, while a cell-hydrogel construct with E of 0.7  kPa generated scar-like tissue. Overall, the results of this study will be highly useful for designing advanced tissue engineering scaffolds that can enhance the quality of a wide array of regenerated tissues including skin.

circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.

Heart failure secondary to myocardial injuries is a leading cause of death worldwide. Recently, a growing number of novel therapies have emerged for injured myocardium repairment. However, delivering therapeutic agents specifically to the injured heart remains a significant challenge. Nanoparticles are the most commonly used vehicles for targeted drug delivery. Various nanoparticles have been synthesized to deliver drugs and other therapeutic molecules to the injured heart via passive or active targeting approaches, and their targeting specificity and therapeutic efficacies have been investigated. Here, we summarized nanoparticle-based, cardiac-specific drug delivery systems, their potency for treating heart diseases, and the mechanisms underlying these cardiac-targeting strategies. We also discussed the clinical studies that have employed nanoparticle-based cardiac-specific drug delivery.