Exosomes are small extracellular nanovesicles that are released by cells, and their potential has been explored for use in cosmetics, skin care, tissue regeneration, and dermatological diseases. The therapeutic value of exosomes lies in their ability to modulate the microenvironment of cells, regulate gene expression, and induce cell differentiation, which can have a positive impact on skin health. In terms of cosmetics, exosomes have been used to reduce wrinkles, improve skin texture and hydration, and enhance skin elasticity, as well as to reduce inflammation and damage caused by UV radiation. Furthermore, exosomes have been used to promote tissue regeneration in skin wounds and to treat dermatological diseases such as systemic lupus erythematosus, psoriasis, atopic dermatitis, systemic sclerosis, pigment regulation, vitiligo, and hair growth. In this review, the therapeutic value of exosomes in the field of cosmetics, skin care, tissue regeneration, and dermatological diseases, has been elaborated. The existing literature demonstrated that with further research, exosomes may become a viable therapeutic option for many skin conditions.

Almost 30% of survivors of myocardial infarction (MI) develop heart failure (HF), in part due to damage caused by the accumulation of dysfunctional mitochondria. Organelle quality control through Parkin-mediated mitochondrial autophagy (mitophagy) is known to play a role in mediating protection against HF damage post-ischaemic injury and remodelling of the subsequent deteriorated myocardium. This study has shown that a single i.p. dose (2 h post-MI) of the selective small molecule Parkin activator PR-364 reduced mortality, preserved cardiac ejection fraction, and mitigated the progression of HF. To reveal the mechanism of PR-364, a multi-omic strategy was deployed in combination with classical functional assays using in vivo MI and in vitro cardiomyocyte models. In vitro cell data indicated that Parkin activation by PR-364 increased mitophagy and mitochondrial biogenesis, enhanced adenosine triphosphate production via improved citric acid cycle, altered accumulation of calcium localization to the mitochondria, and initiated translational reprogramming with increased expression of mitochondrial translational proteins. In mice, PR-364 administered post-MI resulted in widespread proteome changes, indicating an up-regulation of mitochondrial metabolism and mitochondrial translation in the surviving myocardium. This study demonstrates the therapeutic potential of targeting Parkin-mediated mitophagy using PR-364 to protect surviving cardiac tissue post-MI from progression to HF. Parkin activator proposed therapeutic mechanisms. Inactive Parkin (red) is activated by PR-364; activated Parkin (green) promotes enhanced mitophagy and mito-biogenesis, improves mitochondrial function via increased mitochondrial calcium level and biogenesis, and ultimately leads to limited post-myocardial infarction cardiac remodelling and heart failure. MI, myocardial infarction.

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology. Our analysis confirmed that differentiated cells have a proteomic profile more similar to healthy primary aortic smooth muscle cells than iPSCs. We also identified sex-based differences in iPSC-derived vascular smooth muscle cells in pathways related to ATP binding, glycogen metabolic process, and cadherin binding as well as multiple proteins relevant to cardiovascular pathophysiology and disease. Additionally, we explored the role of autosomal and sex chromosomes in protein regulation, identifying that proteins on autosomal chromosomes also show sex-based regulation that may affect the protein expression of proteins from autosomal chromosomes. This work supports the biological relevance of iPSC-derived vascular smooth muscle cells as a model for disease, and further exploration of the pathways identified here can lead to the discovery of sex-specific pharmacological targets for cardiovascular disease.

Myocardial-Infarction (MI) remains a leading cause of mortality worldwide, despite advancements in clinical therapies and interventions. MI results from prolonged ischemia, leading to hypoxia-induced damage to cardiac tissue and reperfusion-injury (R/I) that aggravates cardiomyocyte (CM) loss. One key cellular event during this process is the accumulation of dysfunctional mitochondria, resulting from environmental hypoxia and subsequent oxidative stress upon reperfusion. Post-MI cardiac-remodeling involves changes in both cellular and extracellular matrix (ECM). Ubiquitin-dependent and independent autophagy are crucial for cardio-protection during this phase. Asporin (ASPN), a small leucine-rich proteoglycan, modulates cardiac remodeling by limiting excessive fibrosis and protecting CMs from cell death. We investigated the therapeutic potential of ASPN using an exogenous recombinant ASPN-peptide (rASPN) and tested its effects in an in-vitro ischemia-reperfusion (I/R) model simulating MI conditions. Two I/R models were developed using an immortalized human embryonic cardiac cell line to reflect the hypoxia-reperfusion (H/R) phases of MI. In the No-Reoxygenation (No-ReOx) model, cells were subjected to hypoxia for 18-hours, with or without exogenous rASPN. In the Reoxygenation (ReOx) model, cells underwent 18-hours of hypoxia, followed by 12-hours of reoxygenation (simulating reperfusion), with or without rASPN. Proteomics revealed that ASPN modulates pathways involved in apoptosis, non-canonical autophagy, and metabolic reprogramming. Additionally, ASPN influenced immune-response pathways and significantly affected TGF-β signaling, a central mediator of cardiac fibrosis and remodeling post-MI. Our study demonstrates that rASPN confers protection in a human cardiac cell-based H/R model, highlighting its therapeutic potential as a biological or peptide-based intervention to mitigate R/I and adverse remodeling following MI.