Hexapeptide WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met), a ligand of formyl peptide receptor 2, exhibits anti-inflammatory and angiogenic properties in disease models. However, the therapeutic effects of WKYMVm on hepatic fibrosis have not been evaluated to date. Therefore, we investigated whether WKYMVm exerts antifibrotic effects and induces vascular regeneration in a rat model of bile duct ligation (BDL). The antifibrotic and angiogenic effects of WKYMVm on liver regeneration in the BDL rat model were analyzed using biochemical assays, qRT-PCR, western blotting, immunofluorescence, and immunohistochemistry. To determine the effects of WKYMVm on hepatic fibrosis and angiogenesis in vitro, we measured the expression levels of fibrotic factors in hepatic stellate cells (HSCs) and angiogenic factors in human umbilical vein endothelial cells (HUVECs). WKYMVm attenuated the expression of collagen type I (Col I) and α-smooth muscle actin (α-SMA) and significantly increased the levels of angiogenetic factors in the BDL model (p < 0.05). WKYMVm reduced fibrotic marker expression in transforming growth factor (TGF)-β-induced HSCs and promoted angiogenic activity through tube formation in 5-Fluorouracil (FU)-treated HUVECs (p < 0.05). Also, WKYMVm administration enhanced hepatocyte proliferation in BDL rats (p < 0.05). The WKYMVm alleviates hepatic fibrosis by inhibiting HSC activation and promotes hepatic regeneration via vascular remodeling. These data suggest that the WKYMVm may be a new therapeutic agent for liver fibrosis.

Retinal degenerative diseases result from oxidative stress and mitochondrial dysfunction, leading to the loss of visual acuity. Damaged retinal pigment epithelial (RPE) and photoreceptor cells undergo mitophagy. Pigment epithelium-derived factor (PEDF) protects from oxidative stress in RPE and improves mitochondrial functions. Overexpression of PEDF in placenta-derived mesenchymal stem cells (PD-MSCs; PD-MSCs^PEDF) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCs^PEDF restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H₂O₂)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCs^PEDF augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H₂O₂-injured rat model, intravitreal administration of PD-MSCs^PEDF restored total retinal layer thickness compared to that of naïve PD-MSCs. In particular, PTEN-induced kinase 1 (PINK1), which is the major mitophagy marker, exhibited increased expression in retinal layers and RPE cells after PD-MSC^PEDF transplantation. Similarly, expression of the visual cycle enzyme retinol dehydrogenase 11 (RDH11) showed the same patterns as PINK1 levels, resulting in improved visual activity. Taken together, these findings suggest that PD-MSCs^PEDF facilitate mitophagy and restore the loss of visual cycles in H₂O₂-injured rat retinas and RPE cells. These data indicate a new strategy for next-generation MSC-based treatment of retinal degenerative diseases.

Background: Carotid artery stenosis is a dynamic process associated with an increased risk of cardiovascular events. However, knowledge of biomarkers useful for identifying and quantifying high-risk carotid plaques associated with the increased incidence of cerebrovascular events is insufficient. Therefore, the objectives of this study were to evaluate the expression of ATP binding cassette transporter 1 (ABCA1) and validate its target microRNA (miRNA) candidates in human carotid stenosis arteries to identify its potential as a biomarker. Methods: In human carotid stenosis arterial tissues and plasma, the expression of ABCA1 and its target miRNAs (miRNA-33a-5p, 33b-5p, and 148a-3p) were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Results: The expression of ABCA1 was significantly decreased in the plasma of stenosis patients, but its expression was not different in arterial tissues (p < 0.05). However, significantly more target miRNAs were secreted by stenosis patients than normal patients (p < 0.05). Interestingly, lipotoxicity induced by the oleic and palmitic acid (OAPA) or lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) dramatically enhanced the gene expression of adipogenic and inflammatory factors, whereas ABCA1 expression was significantly decreased. Conclusions: Therefore, miRNA-33a-5p, 33b-5p, and 148a-3p represent possible biomarkers of carotid artery stenosis by directly targeting ABCA1.

DNA damage repair is induced by several factors and is critical for cell survival, and many cellular DNA damage repair mechanisms are closely linked. Antioxidant enzymes that control cytokine-induced peroxide levels, such as peroxiredoxins (Prxs) and catalase (CAT), are involved in DNA repair systems. We previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) that overexpress PRL-1 (PRL-1(+)) promote liver regeneration via antioxidant effects in TAA-injured livers. However, the efficacy of these cells in regeneration and the role of Prxs in their DNA repair system have not been reported. Therefore, our objective was to analyze the Prx-based DNA repair mechanism in naïve or PRL-1(+)-transplanted TAA-injured rat livers. Apoptotic cell numbers were significantly decreased in the PRL-1(+) transplantation group versus the nontransplantation (NTx) group (p < 0.05). The expression of antioxidant markers was significantly increased in PRL-1(+) cells compared to NTx cells (p < 0.05). MitoSOX and Prx3 demonstrated a significant negative correlation coefficient (R² = −0.8123). Furthermore, DNA damage marker levels were significantly decreased in PRL-1(+) cells compared to NTx cells (p < 0.05). In conclusion, increased Prx3 levels in PRL-1(+) cells result in an effective antioxidant effect in TAA-injured liver disease, and Prx3 is also involved in repairing damaged DNA.