TGFβ-Treated Placenta-Derived Mesenchymal Stem Cells Selectively Promote Anti-Adipogenesis in Thyroid-Associated Ophthalmopathy

Orbital fibroblasts (OFs) in thyroid-associated ophthalmopathy (TAO) are differentiated from pre-adipocytes and mature adipocytes; increased lipid and fat expansion are the major characteristics of ophthalmic manifestations. Human placental mesenchymal stem cells (hPMSCs) were reported to immunomodulate pathogenesis and suppress adipogenesis in TAO OFs. Here, we prepared transforming growth factor β (TGFβ, 20 ng/mL)-treated hPMSCs (TGFβ-hPMSCs) in order to enhance anti-adipogenic effects in vitro and in TAO mice. TAO OFs were grown in a differentiation medium and then co-cultured with hPMSCs or TGFβ-hPMSCs. TAO OFs were analyzed via quantitative real-time polymerase chain reaction, Oil red O staining, and western blotting. The results showed that TGFβ-hPMSCs reduced the expression of adipogenic, lipogenic, and fibrotic genes better than hPMSCs in TAO OFs. Moreover, the adipose area decreased more in TAO mice injected with TGFβ-hPMSCs compared to those injected with hPMSCs or a steroid. Further, TGFβ-hPMSCs inhibited inflammation as effectively as a steroid. In conclusion, TGFβ-hPMSCs suppressed adipogenesis and lipogenesis in vitro and in TAO mice, and the effects were mediated by the SMAD 2/3 pathways. Furthermore, TGFβ-hPMSCs exhibited anti-inflammatory and anti-fibrotic functions, which suggests that they could be a new and safe method to promote the anti-adipogenic function of hPMSCs to treat TAO patients.     

A numerical study of a semi‐algebraic multilevel preconditioner for the local discontinuous Galerkin method

In this work, we consider the local discontinuous Galerkin (LDG) method applied to second‐order elliptic problems arising in the modeling of single‐phase flows in porous media. It has been recently proven that the spectral condition number of the stiffness matrix exhibits an asymptotic behavior of ??(h^?2) on structured and unstructured meshes, where h is the mesh size. Thus, efficient preconditioners are mandatory. We present a semi‐algebraic multilevel preconditioner for the LDG method using local Lagrange‐type interpolatory basis functions. We show, numerically, that its performance does not degrade, or at least the number of iterations increases very slowly, as the number of unknowns augments. The preconditioner is tested on problems with high jumps in the coefficients, which is the typical scenario of problems arising in porous media. Copyright © 2007 John Wiley & Sons, Ltd.     

DEPP functionally graded piezoceramics via micro-fabrication by co-extrusion

This paper introduces the Dual Electro/Piezo Property (DEPP) gradient technique via Micro-Fabrication through Co-eXtrusion (MFCX) which pairs a high displacement lead zirconate titanate (PZT) piezoceramic with a high permittivity barium titanate (BT) dielectric. By grading with this material combination spatially across an actuator, the electric field is concentrated in the more active region for improved efficiency, higher displacements, and complex motions. To aid in synthesis and analysis of any gradient profile, compositional maps are provided for key material properties (density, stiffness, permittivity, and piezoelectric coefficients). The DEPP technique was validated, independent of the MFCX process, by powder pressing a conventional bimodal gradient beam which demonstrated through experiments high displacement capabilities at lower driving potentials than comparable functionally graded piezoceramic actuators. For more complex gradients, the MFCX process was adapted to the DEPP gradient technique and illustrated by the fabrication of a linearly graded prototype whose monolithic nature and gradual material variation significantly reduces internal stresses, improves reliability, and extends service lifetime.     

Exciton storage by Mn(2+) in colloidal Mn(2+)-doped CdSe quantum dots

Colloidal Mn (2+)-doped CdSe quantum dots showing long excitonic photoluminescence decay times of up to tau exc = 15 mus at temperatures over 100 K are described. These decay times exceed those of undoped CdSe quantum dots by approximately 10 (3) and are shown to arise from the creation of excitons by back energy transfer from excited Mn (2+) dopant ions. A kinetic model describing thermal equilibrium between Mn (2+ 4)T 1 and CdSe excitonic excited states reproduces the experimental observations and reveals that, for some quantum dots, excitons can emit with near unity probability despite being approximately 100 meV above the Mn (2+ 4)T 1 state. The effect of Mn (2+) doping on CdSe quantum dot luminescence at high temperatures is thus completely opposite from that at low temperatures described previously.     

Green Synthesis of Silymarin–Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis

Background: Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential. Aim: Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL’s anti-fibrotic effectiveness in rats with CCl₄-induced liver fibrosis. Methods: The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days. Results: The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl₄-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFβR1, COL3A1, and TGFβR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study. Conclusions: According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis.     

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.     

Dried Blood Spots as Matrix for Evaluation of Valproate Levels and the Immediate and Delayed Metabolomic Changes Induced by Single Valproate Dose Treatment

The immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified. In male rats, changes in 2-hydroxybutyric acid, pipecolic acid, tetratriacontane and stearic acid were found between the control and treatment groups at various time points from 2.5 h up to 24 h. In contrast, such differences were not observed in female rats, which could be caused by the vast inter-individual variations in metabolite levels within the female group. Based on the measured DBS drug concentrations, clearance and apparent volume of distribution of VPA were estimated and the values were found to be comparable to those estimated previously from full blood drug concentrations. The current study indicated that DBS is a powerful tool to monitor drug levels and metabolic changes in response to drug treatment.