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Abstract

The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24h, 48h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 levels in the serum. Tubular cell proliferation and apoptosis were identified by Ki67 immunostaining and TUNEL assay. Renal fibrosis was assessed by Masson s tri-chrome straining and alpha-smooth muscle actin (alpha-SMA) staining. The infiltration of inflammatory cells was detected by CD68+ staining. The transforming growth factor (TGF)-beta, hepatocyte growth factor (HGF), and alpha-SMA expression in the kidney was measured by Western blot. After renal transplantation, the rats treated with hWJMSCs-MVs improved survival rate and renal function. Moreover, MVs mitigated renal cell apoptosis, enhanced proliferation, and alleviated inflammation at the first 48h. In the late period, abrogation of renal fibrosis was observed in the MVs group. MVs also could decrease the number of CD68+ macrophages in the kidney. Furthermore, MVs decreased the protein expression levels of alpha-SMA and TGF-beta1 and increased the protein expression level of HGF at any point (24 h, 48 h, 1 or 2 weeks). The administration of MVs immediately after renal transplantation could ameliorate IRI in both the acute and chronic stage.

Maternal hypertrophy and diastolic disfunction and brain natriuretic peptide concentration in early and late Pre-Eclampsia

Posted by V.T.M.Borges, S.G.Zanati MD, J.R.Poiati MS, et al. on 2017-12-18 00:25:37

ABSTRACT

Objective: Pre-eclampsia is associated with maternal cardiac remodelling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and Brain Natriuretic Peptide (BNP) levels in women with early-onset pre-eclampsia (<34 weeks of gestation) and late-onset pre-eclampsia (≥34weeks of gestation).

Methods: A prospective, cross-sectional observational study was performed in 30 women with early-onset pre-eclampsia, 32 with late-onset pre-eclampsia and 23 normotensive controls. Maternal cardiac structure and diastolic function as assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay.

Results: Pre-eclampsia was associated with an increased left ventricular mass index and relative wall thickness in early-onset pre-eclampsia compared with late-onset pre-eclampsia and normotensive controls. The prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher in early-onset pre-eclampsia than in late-onset pre-eclampsia (16% for both, all p<0.05). Maternal serum BNP values were also significantly higher in early-onset pre-eclampsia (p<0.05) and correlated with relative wall thickness and left ventricular mass index.

Conclusions: Early-onset pre-eclampsia has more severe cardiac impairment than late-onset pre-eclampsia as evidenced by increased prevalence of concentric hypertrophy, diastolic dysfunction and high concentrations BNP. These findings suggest that early-onset pre-eclampsia causes greater myocardial damage increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility.

Possible Protective Mechanisms exerted by Metformin or Metformin and Vitamin E in Isoproterenol-Induced Cardiac Injury?

Posted by N M.Al-Rasheed, N M.Al-Rasheed, D A.AL-Rabeeah, et al. on 2017-12-18 00:21:54

Abstract

Several studies have reported that metformin is cardioprotective for diabetic and non-diabetic ischemic hearts through mechanisms that cannot be entirely attributed to its anti-hyperglycemic effect. This study was designed to investigate the cardioprotective effects of metformin with and without vitamin E after induction myocardial infarction (MI) in rats, using isoproterenol. Administration of metformin or vitamin E significantly reduced the cardiac mass index (P<0.01), ameliorated the changes to cardiac biomarkers, and attenuated oxidative stress levels compared to the isoproterenol group. Interestingly, combination therapy showed a slight synergistic effect. Histopathological analysis suggested that metformin treatment reduced NF-kB expression and protected against isoproterenol-induced MI. Our results indicate that metformin mediates a cardioprotective effect against isoproterenol-induced MI via antioxidant activity and modulation of the NF-kB signaling pathway. This suggests that metformin would be beneficial in MI treatment. This article is protected by copyright. All rights reserved

5-Azacytidine-mediated hMSC behavior on electrospun scaffolds for skeletal muscle regeneration

Posted by I Fasolino, V Guarino, V Cirillo, et al. on 2017-12-18 00:16:32

Abstract

Incomplete regeneration after trauma or muscular dysfunction is a common problem in muscle replacement therapies. Recent approaches in tissue engineering allow for the replication of skeletal muscle structure and function in vitro and in vivo by molecular therapies and implantable scaffolds which properly address muscle cells toward myotube differentiation and maturation. Here, we investigate the in vitro response of human mesenchymal stem cells (hMSC) on electrospun fibers made of polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to evaluate how fibrous network may influence the therapeutic effect of drug during in vitro myogenesis. Biological studies demonstrate the ability of hMSCs to differentiate in mature myofibers in supplemented (myogenic) and, preferentially, in 5-AZA-enriched culture. PCL electrospun fibers amplify the 5-AZA capability to induce a low proliferation rate in hMSC, thus promoting hMSC differentiation (MTT assay). Qualitative (Azan Mallory stain, immunofluorescence assay, SEM analyses) and quantitative (ELISA test) assays confirm the synergistic contribution of PCL electrospun fibers and 5-AZA on in vitro myotubes formation and maturation. This result is also confirmed by the expression of muscle-specific proteins related to the myogenic mechanisms in the presence of other muscle inductive signals (i.e., oxytocin, Tweak). Hence, we suggest the use of PCL electrospun fibers as interesting preclinical model to explore the effect of drugs and chemotherapeutics administration after damaged muscle resection. 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2551–2561, 2017.

Abstract

Chemobrain refers to a common sequelae experienced by 15–80% of cancer patients exposed to chemotherapeutics. The antineoplastic agent doxorubicin (DOX) has been implicated in a strenuous neurotoxicity manifested as decline in cognitive functions, most probably via cytokine-induced oxidative and nitrosative damage to brain tissues. Astaxanthin (AST), a naturally occurring carotenoid, is reputable for its outstanding antioxidant, anti-inflammatory, and antiapoptotic activities. Therefore, the aim of the current study was to investigate the potential neuroprotective and memory-enhancing effects of AST against DOX-induced behavioral and neurobiological abnormalities. Briefly, AST treatment (25 mg/kg) significantly protected against DOX-induced memory impairment. Furthermore, AST restored hippocampal histopathological architecture, halted DOX-induced oxidative and inflammatory insults, mitigated the increase in acetylcholinesterase activity, and consistently downregulated the overactive apoptotic machineries. In conclusion, these findings suggest that AST offers neuroprotection against DOX-induced cognitive impairment which could be explained at least partly by its antioxidant, anti-inflammatory, and antiapoptotic effects.

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