Aminoalcohol derivatives by nickel-catalyzed enantioselective coupling of imines and dienol ethers.

The reductive coupling of dienol ethers with N-tosylimines catalyzed by Ni(0) in the presence of a VAPOL-derived phosphoramidite ligand follows an unprecedented regiochemical course; it furnishes syn-configured 1,2-aminoalcohol derivatives in good chemical yields with up to 94% ee.

How to avoid prostate biopsy in men with Prostate Image-Reporting and Data System 3 lesion? Development and external validation of new biopsy indication using prostate health index density.

Background: To develop a customized prostate biopsy indication using prostate health index density (PHID) combined with multiparametric magnetic resonance imaging (mpMRI) and assess the reliability of the PHID cutoff value in external populations. Methods: A total of 521 cognitive MRI/ultrasonography fusion prostate biopsies and biomarker tests for prostate-specific antigen (PSA), free PSA, and PHI were performed after mpMRI. The predictive value for clinically significant prostate cancer (csPCa; Gleason score≥7) of PSA derivatives was examined using the ROC curve. We developed a new biopsy indication utilizing a PHID cutoff based on the Prostate Image-Reporting and Data System (PI-RADS) score, which was externally validated. Results: The combination of PHID and mpMRI (AUC = 0.884) demonstrated the highest predictive ability for csPCa, although PHID (AUC = 0.843) and PI-RADS (AUC = 0.806) individually also showed a high diagnostic value. When a PHID cutoff of 0.75 was used in men with PI-RADS 3 lesions, the negative predictive value of csPCa was 100%, and approximately half of the biopsies could be safely avoided. Conclusion: Compared to PHID or PI-RADS scores alone, the combination of PHID and PI-RADS scores increased the accuracy of csPCa detection and the number of cases in which biopsy could be avoided. In men with PI-RADS 3 lesions, the optimal PHID cutoff ≥0.75 can prevent half of the unnecessary biopsies without missing csPCa. In men with PI-RADS 4-5 lesions, biopsies are warranted regardless of PHID values because csPCa could be accompanied by low PHID.

Incidence and risk factors for pressure injury in hospitalized non-small cell lung cancer patients: A retrospective observational study.

AIM: This study aimed to identify the incidence and risk factors for pressure injury in patients hospitalized for non-small cell lung cancer (NSCLC). METHODS: This retrospective observational study was conducted in 645 adults who were hospitalized for NSCLC. Clinicopathological characteristics were compared between NSCLC patients with pressure injury and those without pressure injury. RESULTS: Among total 645 patients, 180 patients showed pressure injury with an incidence of 27.9%. Patients with pressure injury showed increased serum C-reactive protein (CRP) levels (P < 0.001), increased neutrophil-lymphocyte ratio (P = 0.002), and increased platelet-lymphocyte ratio (P = 0.001) more often. Increase in serum CRP levels at the time of admission was the major risk factor for development of pressure injury in NSCLC patients (OR = 2.20; 95% CI [1.40-3.45]; P = 0.001). Also, among major inflammatory markers, serum CRP levels at the time of admission showed weak negative correlation with the period from admission to the development of pressure injury (r = -0.216, P = 0.004). CONCLUSION: By checking serum CRP levels at the time of admission, the NSCLC patients at high risk for the development of pressure injury can be identified in advance and the occurrence of pressure injury can be reduced by applying more active preventive nursing care. CLINICAL TRIAL REGISTRATION NUMBER: KCT0006570.

Increased PRL-1 in BM-derived MSCs triggers anaerobic metabolism via mitochondria in a cholestatic rat model.

Mesenchymal stem cell (MSC) therapy in chronic liver disease is associated with mitochondrial anaerobic metabolism. Phosphatase of regenerating liver-1 (PRL-1), known as protein tyrosine phosphatase type 4A, member 1 (PTP4A1), plays a critical role in liver regeneration. However, its therapeutic mechanism remains obscure. The aim of this study was to establish genetically modified bone marrow (BM)-MSCs overexpressing PRL-1 (BM-MSCsPRL-1) and to investigate their therapeutic effects on mitochondrial anaerobic metabolism in a bile duct ligation (BDL)-injured cholestatic rat model. BM-MSCsPRL-1 were generated with lentiviral and nonviral gene delivery systems and characterized. Compared with naive cells, BM-MSCsPRL-1 showed an improved antioxidant capacity and mitochondrial dynamics and decreased cellular senescence. In particular, mitochondrial respiration in BM-MSCsPRL-1 generated using the nonviral system was significantly increased as well as mtDNA copy number and total ATP production. Moreover, transplantation of BM-MSCsPRL-1 generated using the nonviral system had predominantly antifibrotic effects and restored hepatic function in a BDL rat model. Decreased cytoplasmic lactate and increased mitochondrial lactate upon the administration of BM-MSCsPRL-1 indicated significant alterations in mtDNA copy number and ATP production, activating anaerobic metabolism. In conclusion, BM-MSCsPRL-1 generated by a nonviral gene delivery system enhanced anaerobic mitochondrial metabolism in a cholestatic rat model, improving hepatic function.

Metachronous Contralateral Occurrence of Hydrocele After Unilateral Hydrocelectomy in Children Younger Than 8 Years.

BACKGROUND: Hydrocele on the contralateral side after surgical repair is an uncommon condition compared to surgical site recurrence. Although there has been much research on metachronous contralateral inguinal hernia in children, metachronous contralateral hydrocele, which share a common pathology with inguinal hernias, has not yet been investigated. We have investigated the incidence and risk factors for metachronous contralateral occurrence of communicating and noncommunicating hydroceles in children younger than 8 years. METHODS: From January 2017 to June 2020, 302 children younger than 8 who were diagnosed with unilateral hydroceles were treated in our hospital without surgical exploration of contralateral hydrocele. The disease was classified into communicating and noncommunicating hydroceles. We divided patients into two groups according to the presence of metachronous contralateral hydrocele and analyzed the differences between the two groups. RESULTS: Among 302 patients, the mean age was 36.4 ± 20.9 months. Metachronous contralateral hydrocele occurred in 15 (4.9%) patients as communicating hydroceles. Comparison between the two groups showed statistically significant differences in type of hydrocele (P = 0.047) at first diagnosis. CONCLUSION: Clinically evident risk of metachronous contralateral hydrocele after unilateral hydrocelectomy was 4.9%. Despite the relatively low incidence rate, the risk of metachronous contralateral occurrence should always be consulted with parents before surgical treatment of hydroceles.

Enhanced delivery of the phototherapeutic nanoparticles via hepatocyte overload.

Phototherapeutic nanoparticles (NPs) were prepared with methylene blue (MB), indocyanine green (ICG), and Solutol through self-assembly. Generation of reactive oxygen species and elevation of temperature were observed that verify the photodynamic/photothermal effects of the NPs. Morphology and size distribution of the NPs were examined by transmittance electron microscopy and dynamic light scattering. The biodistribution of the NPs and their antitumor efficacy were examined using tumor-bearing mice to understand the phototherapeutic effect of the NPs on tumors. To enhance targetability with enhanced therapeutic efficacy, empty NPs (Solutol nanoparticles without MB and ICG) at different concentrations were injected along with the phototherapeutic NPs. Enhanced delivery of the phototherapeutic NPs at the tumor site was examined based on hepatocyte overload.

The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy.

PURPOSE: Persistent levels of prostate-specific antigen (PSA) is a poor prognostic factor for recurrence after radical prostatectomy (RP). We investigated the impact of the percentage of residual PSA (%rPSA) [(post-/preoperative PSA)×100], representing a biochemical residual tumor, and the first postoperative PSA (fPSA) level on metastasis-free survival (MFS) in men with persistent levels of PSA after RP. MATERIALS AND METHODS: We retrospectively identified male patients within a single tertiary referral hospital database who harbored persistent (≥0.1 ng/mL) vs. undetectable (<0.1 ng/mL) PSA levels 4 to 8 weeks after RP. Kaplan-Meier analyses and Cox regression models were used to test the effect of persistent PSA levels, the fPSA level, and %rPSA on MFS. RESULTS: Of 1,205 patients, 178 patients with persistent PSA levels were enrolled. Seven-year MFS rates were 60.5% vs. 84.3% (p<0.001) for patients with a %rPSA ≥6% and <6%, respectively. Multivariable Cox regression models of the overall cohort revealed that persistent PSA levels (hazard ratio [HR], 3.94; p=0.010), extracapsular extension (HR, 4.17; 95% confidence interval [CI], 1.06-16.41; p=0.041), and pathological Gleason grade group (pGGG) (HR, 3.69; 95% CI, 1.32-10.27; p=0.013) were independent predictors of metastasis. Multivariable Cox regression models in men with persistent PSA levels revealed that the %rPSA (HR, 8.92; 95% CI, 1.74-45.71; p=0.009) and pGGG 4-5 (HR, 4.13; 95% CI, 1.22-13.96; p=0.022) were independent predictors of distant metastasis, but not the fPSA level after surgery. CONCLUSIONS: Persistent levels of PSA were associated with worse MFS after RP. In men with persistent PSA levels after RP, the %rPSA is a valuable predictor of MFS unlike the fPSA level.

Nickel-Catalyzed Enantioselective Coupling of Aldehydes and Electron-Deficient 1,3-Dienes Following an Inverse Regiochemical Course.

The nickel catalyzed reductive coupling of aldehydes with sorbate esters and related electron-deficient 1,3-dienes are known in the literature to occur at the π-bond proximal to the ester to afford aldol-type products. In stark contrast to this established path, a VAPOL-derived phosphoramidite ligand in combination with a bench-stable nickel precatalyst brokers a regiocomplementary course in that C-C bond formation proceeds exclusively at the distal alkene site to give deoxypropionate type products carrying an acrylate handle; they can be made in either anti- or syn-configured form. In addition to this enabling reverse pathway, the reaction is distinguished by excellent levels of chemo-, diastereo-, and enantioselectivity; moreover, it can be extended to the catalytic formation of F3C-substituted stereogenic centers. The use of a dienyl pinacolboronate instead of a sorbate ester is also possible, which opens access to valuable chiral borylated building blocks in optically active form.

External validation of European Association of Urology NMIBC risk scores to predict progression after transurethral resection of bladder tumor in Korean patients with non-muscle-invasive bladder cancer.

PURPOSE: This study aimed to validate the newly proposed risk model in Korean patients diagnosed with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective review was performed with 1,238 patients who underwent transurethral resection of bladder tumor from 2009 to 2020. We included 973 patients and categorized them into four risk groups according to the European Association of Urology (EAU) NMIBC risk stratification standards, which incorporate the World Health Organization 2004/2016 grading classification. Kaplan-Meyer survival analysis and multivariable analysis of time to progression were performed to calculate the probability of progression for all risk groups. RESULTS: A total of 973 patients were followed for 54.85 months. Patients were classified according to the risk factors proposed by the new NMIBC risk table and stratified into low, intermediate, high, and very high-risk groups based on the table. Cancer progression into muscle-invasive bladder cancer (MIBC) in each risk group was observed in 7 (4.4%), 24 (15.2%), 76 (48.1%), and 51 (32.3%) individuals, respectively. The progression rate was distinguishable between risk groups in the Kaplan-Meier progression-free survival analysis, and higher risk was associated with a higher rate of progression. The new NMIBC risk variables were demonstrated to have prognostic value in the multivariate analysis. The very high-risk group was associated with progression to muscle-invasive disease. CONCLUSIONS: This study demonstrates that the new EAU NMIBC risk group categorization is feasible in predicting the progression of NMIBC into MIBC in the Korean population and thus should be applied to clinical practice in Korea.

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development.

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17ß-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

Increased phosphatase regenerating liver-1 trigger vascular remodeling in injured ovary via platelet-derived growth factor signaling pathway.

BACKGROUND: Vascular abnormalities in the ovary cause infertility accompanied by ovarian insufficiency due to a microenvironment of barren ovarian tissues. Placenta-derived mesenchymal stem cells (PD-MSCs, Naïve) treatment in ovarian dysfunction shows angiogenic effect, however, the therapeutic mechanism between ovarian function and vascular remodeling still unclear. Therefore, we examined whether by phosphatase regenerating liver-1 (PRL-1), which is correlated with angiogenesis in reproductive systems, overexpressed PD-MSCs could maximize the angiogenic effects in an ovarian tissues injured of rat model with partial ovariectomy and their therapeutic mechanism by enhanced vascular function via PDGF signaling. METHODS: PD-MSCsPRL-1 (PRL-1) were generated by nonviral AMAXA gene delivery system and analyzed the vascular remodeling and follicular development in ovary. One week after Sprague-Dawley (SD) rats ovariectomy, Naïve and PRL-1 was transplanted. The animals were sacrificed at 1, 3 and 5 weeks after transplantation and vascular remodeling and follicular development were analyzed. Also, human umbilical vein endothelial cells (HUVECs) and ovarian explantation culture were performed to prove the specific effects and mechanism of PRL-1. RESULTS: Vascular structures in ovarian tissues (e.g., number of vessels, thickness and lumen area) showed changes in the Naïve and PRL-1-overexpressed PD-MSC (PRL-1) transplantation (Tx) groups compared to the nontransplantation (NTx) group. Especially, PRL-1 induce to increase the expression of platelet-derived growth factor (PDGF), which plays a role in vascular remodeling as well as follicular development, compared to the NTx. Also, the expression of genes related to pericyte and vascular permeability in arteries was significantly enhanced in the PRL-1 compared to the NTx (p < 0.05). PRL-1 enhanced the vascular formation and permeability of human umbilical vein endothelial cells (HUVECs) via activated the PDGF signaling pathway. CONCLUSIONS: Our results show that PRL-1 restored ovarian function by enhanced vascular function via PDGF signaling pathway. These findings offer new insight into the effects of functionally enhanced stem cell therapy for reproductive systems and should provide new avenues to develop more efficient therapies in degenerative medicine.

Combination Therapy of Placenta-Derived Mesenchymal Stem Cells with WKYMVm Promotes Hepatic Function in a Rat Model with Hepatic Disease via Vascular Remodeling.

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.

Phosphatase of Regenerating Liver-1 (PRL-1)-Overexpressing Placenta-Derived Mesenchymal Stem Cells Enhance Antioxidant Effects via Peroxiredoxin 3 in TAA-Injured Rat Livers.

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.

Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium.

BACKGROUND: Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL-1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL-1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL). METHODS: Liver cirrhosis was induced in Sprague-Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL-1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL-1. RESULTS: ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL-1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL-1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression. CONCLUSIONS: These findings suggest that PD-MSCsPRL-1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.

Increased Phosphatase of Regenerating Liver-1 by Placental Stem Cells Promotes Hepatic Regeneration in a Bile-Duct-Ligated Rat Model.

Phosphatase of regenerating liver-1 (PRL-1) controls various cellular processes and liver regeneration. However, the roles of PRL-1 in liver regeneration induced by chorionic-plate-derived mesenchymal stem cells (CP-MSCs) transplantation remain unknown. Here, we found that increased PRL-1 expression by CP-MSC transplantation enhanced liver regeneration in a bile duct ligation (BDL) rat model by promoting the migration and proliferation of hepatocytes. Engrafted CP-MSCs promoted liver function via enhanced hepatocyte proliferation through increased PRL-1 expression in vivo and in vitro. Moreover, higher increased expression of PRL-1 regulated CP-MSC migration into BDL-injured rat liver through enhancement of migration-related signals by increasing Rho family proteins. The dual effects of PRL-1 on proliferation of hepatocytes and migration of CP-MSCs were substantially reduced when PRL-1 was silenced with siRNA-PRL-1 treatment. These findings suggest that PRL-1 may serve as a multifunctional enhancer for therapeutic applications of CP-MSC transplantation.

Corrosion Inhibition of Mild Steel and 304 Stainless Steel in 1 M Hydrochloric Acid Solution by Tea Tree Extract and Its Main Constituents.

Tea tree extract, containing antioxidant constituents α-terpineol, terpinen-4-ol, and α-terpinene, has a wide range of applications in the cosmetic, food, and pharmaceutical industries. In this study, tea tree extract showed an anticorrosive effect under 1 M HCl solution on mild steel (MS) and 304 stainless steel (STS). Uniform corrosion for MS and pitting corrosion for STS at 298 K were retarded, with inhibition efficiencies of 77% and 86%, respectively. The inhibition of uniform and pitting corrosion was confirmed by scanning electron microscopy and laser scanning confocal microscopy in terms of surface roughness and pitting morphologies. The most effective constituent contributing to the inhibitory performance of tea tree extract was revealed to be α-terpineol, with an inhibition efficiency of 83%. The adsorption of tea tree extract was confirmed by surface characterization analysis using Fourier transform infrared spectroscopy, Raman spectroscopy, and Electrochemical impedance spectroscopy. Interestingly, G- and D-peaks of Raman spectra were detected from the inhibited steels, and this finding is the first example in the corrosion inhibition field. The anticorrosion mechanism can be explained by the formation of organic-Fe complexes on the corroded steel surface via electron donor and acceptor interactions in the presence of an oxygen atom of the hydroxyl group or ether of organic inhibitors.

PEDF-Mediated Mitophagy Triggers the Visual Cycle by Enhancing Mitochondrial Functions in a H2O2-Injured Rat Model.

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-MSCsPEDF) provides therapeutic effects in retinal degenerative diseases. Here, we investigated whether PD-MSCsPEDF restored the visual cycle through a mitophagic mechanism in RPE cells in hydrogen peroxide (H2O2)-injured rat retinas. Compared with naïve PD-MSCs, PD-MSCsPEDF augmented mitochondrial biogenesis and translation markers as well as mitochondrial respiratory states. In the H2O2-injured rat model, intravitreal administration of PD-MSCsPEDF 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-MSCPEDF 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-MSCsPEDF 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.

PRL-1 overexpressed placenta-derived mesenchymal stem cells suppress adipogenesis in Graves' ophthalmopathy through SREBP2/HMGCR pathway.

BACKGROUND: Graves' ophthalmopathy (GO) is a disorder, in which orbital connective tissues get in inflammation and increase in volume. Stimulants such as thyroid-stimulating hormone (TSH), insulin-like growth factor 1(IGF-1), IL-1, interferon γ, and platelet-derived growth factor cause differentiation into adipocytes of orbital fibroblasts (OFs) in the orbital fat and extraocular muscles. Human placental mesenchymal stem cells (hPMSCs) are known to have immune modulation effects on disease pathogenesis. Some reports suggest that hPMSCs can elicit therapeutic effects, but to date, research on this has been insufficient. In this study, we constructed PRL-1 overexpressed hPMSCs (hPMSCsPRL-1) in an attempt to enhance the suppressive function of adipogenesis in GO animal models. METHODS: In order to investigate the anti-adipogenic effects, primary OFs were incubated with differentiation medium for 10 days. After co-culturing with hPMSCsPRL-1, the characteristics of the OFs were analyzed using Nile red stain and quantitative real-time polymerase chain reaction. We then examined the in vivo regulatory effectiveness of hPMSCsPRL-1 in a GO mouse model that immunized by leg muscle electroporation of pTriEx1.1Neo-hTSHR A-subunit plasmid. Human PMSCsPRL-1 injection was performed in left orbit. We also analyzed the anti-adipogenic effects of hPMSCsPRL-1 in the GO model. RESULTS: We found that hPMSCsPRL-1 inhibited adipogenic activation factors, specifically PPARγ, C/EBPα, FABP4, SREBP2, and HMGCR, by 75.1%, 50%, 79.6%, 81.8%, and 87%, respectively, compared with naïve hPMSCs in adipogenesis-induced primary OFs from GO. Moreover, hPMSCsPRL-1 more effectively inhibited adipogenic factors ADIPONECTIN and HMGCR by 53.2% and 31.7%, respectively, than hPMSCs, compared with 15.8% and 29.8% using steroids in the orbital fat of the GO animal model. CONCLUSION: Our findings suggest that hPMSCsPRL-1 would restore inflammation and adipogenesis of GO model and demonstrate that they could be applied as a novel treatment for GO patients.