Patient- and treatment-related factors may influence the longevity of primary teeth restorations in high caries-risk children: A university-based retrospective study.

Purpose: To evaluate the longevity and factors associated with failure of primary teeth restorations placed in high caries-risk children.

Methods: The sample was comprised of children treated in a University Dental Service. Patients' records were screened retrospectively to determine whether they had received restorative treatment in primary teeth presenting cavitated caries lesions.

Silica nanoparticles actively engage with mesenchymal stem cells in improving acute functional cardiac integration.

Aim: To assess functional effects of silica nanoparticles (SiO-NPs) on human mesenchymal stem cell (hMSC) cardiac integration potential.

Methods: SiO-NPs were synthesized and their internalization effects on hMSCs analyzed with particular emphasis on interaction of hMSCs with the cardiac environment Results: SiO-NP internalization affected the area and maturation level of hMSC focal adhesions, accounting for increased in vitro adhesion capacity and augmented engraftment in the myocardial tissue upon cell injection in infarcted isolated rat hearts. SiO-NP treatment also enhanced hMSC expression of Connexin-43, favoring hMSC interaction with cocultured cardiac myoblasts in an ischemia-like environment.

Stem Cell Tracking with Nanoparticles for Regenerative Medicine Purposes: An Overview.

Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies. Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application.

Human mesenchymal stem cells labelled with dye-loaded amorphous silica nanoparticles: long-term biosafety, stemness preservation and traceability in the beating heart.

Background: Treatment of myocardial infarction with mesenchymal stem cells (MSCs) has proven beneficial effects in both animal and clinical studies. Engineered silica nanoparticles (SiO2-NPs) have been extensively used as contrast agents in regenerative medicine, due to their resistance to degradation and ease of functionalization. However, there are still controversies on their effective biosafety on cellular systems.

A New Paradigm in Cardiac Regeneration: The Mesenchymal Stem Cell Secretome.

The potentialities to apply mesenchymal stem cells (MSCs) in regenerative medicine have been extensively studied over the last decades. In the cardiovascular disease (CVD) field, MSCs-based therapy is the subject of great expectations. Its therapeutic potential has been already shown in several preclinical models and both the safety and efficacy of MSCs-based therapy are being evaluated in humans.

Catestatin exerts direct protective effects on rat cardiomyocytes undergoing ischemia/reperfusion by stimulating PI3K-Akt-GSK3β pathway and preserving mitochondrial membrane potential.

Catestatin (Cst) is a 21-amino acid peptide deriving from Chromogranin A. Cst exerts an overall protective effect against an excessive sympathetic stimulation of cardiovascular system, being able to antagonize catecholamine secretion and to reduce their positive inotropic effect, by stimulating the release of nitric oxide (NO) from endothelial cells. Moreover, Cst reduces ischemia/reperfusion (I/R) injury, improving post-ischemic cardiac function and cardiomyocyte survival.

Factors Ruling the Uptake of Silica Nanoparticles by Mesenchymal Stem Cells: Agglomeration Versus Dispersions, Absence Versus Presence of Serum Proteins.

The results of a systematic investigation of the role of serum proteins on the interaction of silica nanoparticles (NP) doped in their bulk with fluorescent molecules (IRIS Dots, 50 nm in size), with human mesenchymal stem cells (hMSCs) are reported. The suspension of IRIS Dots in bare Dulbecco-modified Eagle's medium results in the formation of large agglomerates (≈1.5 μm, by dynamic light scattering), which become progressively smaller, down to ≈300 nm in size, by progressively increasing the fetal bovine serum (FBS) content of the solutions along the series 1.

Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in various tissues, including the bone marrow. In contrast to terminally differentiated somatic cells, adult stem cells must persist and function throughout life to ensure tissue homeostasis and repair. For this reason, they must be equipped with DNA damage responses able to maintain genomic integrity while ensuring their lifelong persistence.

Obligatory role for endothelial heparan sulphate proteoglycans and caveolae internalization in catestatin-dependent eNOS activation.

The chromogranin-A peptide catestatin modulates a wide range of processes, such as cardiovascular functions, innate immunity, inflammation, and metabolism. We recently found that the cardiac antiadrenergic action of catestatin requires a PI3K-dependent NO release from endothelial cells, although the receptor involved is yet to be identified. In the present work, based on the cationic properties of catestatin, we tested the hypothesis of its interaction with membrane heparan sulphate proteoglycans, resulting in the activation of a caveolae-dependent endocytosis.

The effect of bioartificial constructs that mimic myocardial structure and biomechanical properties on stem cell commitment towards cardiac lineage.

Despite the enormous progress in the treatment of coronary artery diseases, they remain the most common cause of heart failure in the Western countries. New translational therapeutic approaches explore cardiomyogenic differentiation of various types of stem cells in combination with tissue-engineered scaffolds. In this study we fabricated PHBHV/gelatin constructs mimicking myocardial structural properties.

Regulation of intracellular cardiomyocyte calcium stores by peptides: a new approach to cardiac protection.

The control of cytosolic calcium is a major determinant not only of cardiac function, but also of the capability of myocardial tissue to survive damage. Increase of diastolic calcium leads rapidly to cell injury, and may be induced by a wide range of causes. In this review we describe the major points of calcium control in cardiac myocytes, mainly in mammalian ventricle, focusing on mechanisms of intracellular calcium influx during excitation, voltage gated channels of the sarcolemma and ryanodine receptors of the sarcoplasmic reticulum (SR), and efflux during relaxation, principally the sodium/calcium exchanger in membrane and the SR calcium complex.

Development of morphology and function of neonatal mouse ventricular myocytes cultured on a hyaluronan-based polymer scaffold.

In recent years cardiac tissue engineering has emerged as a promising field aimed at developing suitable techniques to repair the infarcted myocardium with a combination of cells, biomaterials, and regulative factors. In particular it could stand for an alternative strategy to simple in situ cellular implantation. In the present study our purpose was to analyze the interaction between a hyaluronan-based mesh (HYALONECT®) and neonatal murine ventricular myocytes (NMVMs).

Analysis of interactions between ribosomal proteins and RNA structural motifs.

Background: One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in T.

Low-level laser therapy for implants without initial stability.

Objective: This study evaluated the effect of low-level infrared laser on removal torque values of implants with poor initial stability inserted in rabbit tibias.

Background Data: It is important to analyze the effects of laser radiation on bone repair when low-quality bone and implants with poor initial stability are used.

Materials And Methods: Thirty male white New Zealand rabbits (Oryctolagus Cuniculus) about 2 mo old and weighing 1.

Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors.

To evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC(50) in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC(50) of 20 microM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs.

Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new insights from molecular dynamics simulations.

Molecular Dynamics simulations in aqueous solution were performed for the matrix metalloproteinase-8 (MMP-8) free catalytic domain and for its complexes with the (R)- and (S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate. The 144-155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with both enantiomers. The two enantiomers induce a different decrease of conformational entropy upon complexation.

alpha-Biphenylsulfonylamino 2-methylpropyl phosphonates: enantioselective synthesis and selective inhibition of MMPs.

(R)-alpha-Biphenylsulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, alpha-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA.

Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates.

Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues.

N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8.

The first crystallographic structure of an N-hydroxyurea inhibitor bound into the active site of a matrix metalloproteinase is reported. The ligand and three other analogues were prepared and studied as inhibitors of MMP-2, MMP-3, and MMP-8. The crystal structure of the complex with MMP-8 shows that the N-hydroxyurea, contrary to the analogous hydroxamate, binds the catalytic zinc ion in a monodentate rather than bidentate mode and with high out-of-plane distortion of the amide bonds.

AMBER force field implementation of the boronate function to simulate the inhibition of beta-lactamases by alkyl and aryl boronic acids.

Boronic acids are a very appealing class of serine proteases inhibitors whose rational design suffers, in spite of their therapeutic potential, from the lack of boron-related parameters in force fields commonly used for proteins. We introduced bonded, non-bonded and point charges in the MacroModel/Amber force field, as well as GB/SA solvation parameters, to model boronic acids as tetrahedral adducts formed after protease's serine Ogamma coordination. With the aim to check the implemented force field, flexible docking studies were performed on three crystallographic complexes of beta-lactamases with boronic acids that output the crystallographic conformation of the complexes as the global minimum energy structure.

Design, modelling, synthesis and biological evaluation of peptidomimetic phosphinates as inhibitors of matrix metalloproteinases MMP-2 and MMP-8.

Three novel peptidomimetic phosphinate inhibitors have been synthesized and evaluated as inhibitors of matrix metalloproteinases MMP-2 and MMP-8. Their IC50 values are in the micromolar range, and one of them showed to be the most effective inhibitor of MMP-2. The differences in binding affinities for MMP-2 and MMP-8 of the three phosphinates have been rationalized by means of modelling studies and molecular dynamics simulations.

Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2.

The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)(2) (2b) was reported as the first example of left-hand-sideLeft-hand-side inhibitors: inhibitors that bind in the unprime region of the enzyme active site, in reference to the convention of drawing the unprimed residues of a peptide substrate on the left side. [R.P.

Computational study of the catalytic domain of human neutrophil collagenase. specific role of the S3 and S'3 subsites in the interaction with a phosphonate inhibitor.

Human neutrophil collagenase (HNC, MMP-8) is one of the target enzymes for drug treatment of pathologic extracellular matrix degradation. Peptidomimetic inhibitors bind in the S'-side of the enzyme active site occupying the S'1 primary specificity pocket by their large hydrophobic side-chains. The crystal structure of the complex between the catalytic domain of MMP-8 and Pro-Leu-L-TrpP(OH)2 (PLTP) showed that this phosphonate inhibitor binds in the S side of the active site.