Translational research : the journal of laboratory and clinical medicine
-
Cardiac fibrosis is a process characterized by extracellular matrix accumulation leading to myocardial dysfunction. Angiotensin II (Ang II) has been shown to play an important role in the pathogenesis of cardiac fibrosis. However, the underlying mechanisms are not well established. ⋯ Bioinformatics analysis and further validation experiments revealed that RAP1 is a direct downstream target of miR-23a-3p, and overexpression of RAP1 reversed the profibrotic effect of miR-23a-3p. Taken together, these findings elucidated the role of eWAT in Ang II-induced myocardial fibrosis and indicated that adipocyte-derived exosomes mediate pathologic communication between dysfunctional adipose tissue and the heart by transporting miR-23a-3p into CFs, transforming fibroblasts into myofibroblasts and promoting excessive collagen deposition by targeting RAP1. Prevention of abnormal adipocyte exosome production, inhibition of miR-23a-3p biogenesis, and treatment with a miR-23a-3p antagonist are novel strategies for treating cardiac fibrosis.
-
Currently, there are very few well-established treatments to stimulate corneal endothelial cell regeneration in vivo as a cure for corneal endothelial dysfunctions. The most frequently performed intervention for a damaged or dysfunctional corneal endothelium nowadays is corneal endothelial keratoplasty, also known as lamellar corneal transplantation surgery. Newer medical therapies are emerging and are targeting the regeneration of the corneal endothelium, helping the patients regain their vision without the need for donor tissue. ⋯ However, the literature offers little guidance and selective attention to the question of how to fully exploit these pathways. The purpose of this paper is to provide an overview of wound healing characteristics from a biochemical level in the lab to the regenerative features seen in the clinic. Studying the pathways involved in corneal wound healing together with their key effector proteins, can help explain the effect on the proliferation and migration capacity of the corneal endothelial cells.
-
Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. ⋯ Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.
-
Gender-sex differences in autoimmune diseases are gaining increasing attention due to their effects on prevalence and clinical features. Data on gender-sex differences in autoimmune atrophic gastritis (AAG), a chronic not-self-limiting inflammatory condition characterized by corpus-oxyntic mucosa atrophy sparing the antrum, are lacking. This study aimed to assess possible gender-sex differences of clinical, serological, histological, and genetic features in AAG patients. ⋯ AAG was preponderant in women who showed stronger autoimmune serological responsiveness and different HLA-DRB1 association. AAG showed differential clinical profiles in female and male patients occurring mainly in normal weight, dyspeptic women with iron-deficiency anemia and autoimmune thyroid disease, but in overweight male smokers with pernicious anemia. Stratification for sex and gender should be considered in future genetic, immunological, and clinical studies on autoimmune atrophic gastritis.
-
Multiple SARS-CoV-2 variants are identified with higher rates of transmissibility or greater disease severity. Particularly, recent emergence of Omicron variant with rapid human-to-human transmission posts new challenges to the current prevention strategies. In this study, following vaccination with an mRNA vaccine encoding SARS-CoV-2 receptor-binding domain (RBD-mRNA), we detected serum antibodies that neutralized pseudoviruses expressing spike (S) protein harboring single or multiple mutations, as well as authentic SARS-CoV-2 variants, and evaluated its protection against SARS-CoV-2 infection. ⋯ Particularly, RBD-mRNA vaccine completely protected mice from challenge with a virulent mouse-adapted SARS-CoV-2 variant. Among these lineages, B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529 belong to Alpha, Beta, Gamma, Delta, and Omicron variants, respectively. Our observations reveal that RBD-mRNA vaccine is promising and highlights the need to design novel vaccines with improved neutralization against current and future pandemic SARS-CoV-2 variants.