SFRP1-Silencing GapmeR-Loaded Lipid-Polymer Hybrid Nanoparticles for Bone Regeneration in Osteoporosis: Effect of Dosing and Targeting Strategy.

Introduction: Osteoporosis is a metabolic disorder characterized by the loss of bone mass and density. Nucleic acid-based therapies are among the most innovative approaches for osteoporosis management, although their effective delivery to bone tissue remains a challenge. In this work, SFRP1-silencing GampeR loaded-nanoparticles were prepared and functionalized with specific moieties to improve bone targeting and, consequently, therapeutic efficacy.

Dorsal root ganglion inflammation by oxaliplatin toxicity: DPEP1 as possible target for peripheral neuropathy prevention.

Background: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency.

Iohexol plasma clearance simplified by Dried Blood Spot (DBS) sampling to measure renal function in conscious mice.

There is no simple method to measure glomerular filtration rate (GFR) in mice, which limits the use of mice in models of renal diseases. We aimed at simplifying the plasma clearance of iohexol in mice, using dried blood spot (DBS) sampling in order to reduce the amount of blood taken for analysis. GFR was measured simultaneously by a reference method in total blood-as described before-and tested method using DBS in fifteen male and six female C57BL/6J mice.

Alginate-hydrogel versus alginate-solid system. Efficacy in bone regeneration in osteoporosis.

In the present study, two different PLGA-Alginate scaffolds, a hydrogel (HY) and a solid sponge (SS), were developed for β-estradiol and BMP-2 sustained delivery for bone regeneration in osteoporosis. β-Estradiol and BMP-2 were encapsulated in PLGA and PLGA-Alginate microspheres respectively. Scaffolds were characterized in vitro in terms of porosity, water uptake, release rate and HY rheological properties.

Injectable Scaffold for Bone Marrow Stem Cells and Bone Morphogenetic Protein-2 to Repair Cartilage.

Objective: The limits of the microfracture (MFX) treatment in terms of lesion size and long-term tissue functionality makes it necessary to investigate different alternatives to repair focal cartilage lesions. The present study aims at evaluating the efficacy of a minimally invasive approach against the conventional MFX to repair a chondral defect in rabbits. An injectable scaffold of BMP-2 pre-encapsulated in PLGA microspheres dispersed in a Pluronic F-127 solution is proposed as support of cells and controlled delivery system for the growth factor.

In situ gel-forming system for dual BMP-2 and 17β-estradiol controlled release for bone regeneration in osteoporotic rats.

The aim of this study was to evaluate the bone regeneration capacity of a Pluronic® F127 (P)-Tetronic®1307 (T) and α-cyclodextrin (CD) supramolecular gel (P-T-CD) in a 11/7/7 ratio containing BMP-2 and 17β-estradiol pre-encapsulated in poly-lactide-co-glycolide (PLGA) and poly-lactic acid (PLA-S) microspheres, respectively. Ovariectomy combined with dexamethasone treatment was used to induce an osteoporotic (OP) animal model of calvaria critical size defect in female rats to test the system. The two active substances showed a biphasic in vitro release profile characterized by an initial fast phase followed by a slow and prolonged release.

Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control.

Iohexol plasma clearance, a simple and reliable method to measure renal function in conscious mice.

In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice.

Mice lacking chromogranins exhibit increased aggressive and depression-like behaviour.

Chromogranins are acidic proteins; both chromogranins A and B constitute the main protein component in the vesicular matrix of large dense core vesicles. Chromogranins are a natural source of peptides with different physiological activities that have been associated with vascular and neurological diseases. We have used three different genetic mutant models of mice lacking chromogranin A, chromogranin B and both all on the same C57BL/6J background, to characterize the physiological roles of these proteins using metabolic, cardiovascular and behavioural tests.

Ex vivo and in vivo models for endoscopic submucosal dissection training.

Endoscopic submucosal dissection is a technically challenging but highly effective technique for the treatment of well selected early neoplasms in the digestive tract. Although it is frequently performed in East Asian countries, the Western world has not adopted this technique yet, probably due in part to the difficulty to learn it. Ex vivo and in vivo animal models are invaluable tools to overcome at least the beginning of the learning curve, although the initial step is the acquisition of basic knowledge about early diagnosis of neoplasias, and observing real procedures in expert centers.

Endoscopic submucosal dissection training with pig models in a Western country.

Aim: To test a strategy for endoscopic submucosal dissection (ESD) training in animal models designed to overcome the initial learning curve.

Methods: ESD was attempted in ex vivo and in vivo pig models. Thirty ESD procedures were attempted in the esophagus (n = 9) or the stomach (n = 21).

The mineralocorticoid receptor is a constitutive nuclear factor in cardiomyocytes due to hyperactive nuclear localization signals.

The mineralocorticoid receptor (MR), a member of the nuclear receptor family, mediates the action of aldosterone in target epithelia, enhancing sodium reabsorption. In addition, MR may have other physiological functions in nonepithelial tissues. Altered expression or inappropriate activation of cardiac MR is directly linked to the development of cardiac fibrosis, and MR blockade is beneficial for the treatment of heart failure.

Chromogranins as regulators of exocytosis.

Chromogranins (Cgs) constitute the main protein component in the vesicular matrix of large dense core vesicles (LDCV). These acidic proteins have been implicated in several physiological processes such as vesicle sorting, the generation of bioactive peptides and the accumulation of soluble species inside LDCV. This latter feature of Cgs accounts for the ability of vesicles to concentrate catecholamines and Ca(2+).

Impact on allergic immune response after treatment with vitamin A.

Background: Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear.

Objective: To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease.

Methods: Ovalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.

Similar response in male and female B10.RIII mice in a murine model of allergic airway inflammation.

Background: Several reports have been published on the gender differences associated with allergies in mice.

Goal: In the present study we investigate the influence of gender on allergy response using a strain of mice, B10.RIII, which is commonly used in the collagen-induced arthritis murine model.

Interspecific recombinant congenic strains between C57BL/6 and mice of the Mus spretus species: a powerful tool to dissect genetic control of complex traits.

Complex traits are under the genetic control of multiple genes, often with weak effects and strong epistatic interactions. We developed two new collections of mouse strains to improve genetic dissection of complex traits. They are derived from several backcrosses of the Mus spretus SEG/Pas or STF/Pas strains on the C57BL/6J background.

A new locus for resistance to gamma-radiation-induced thymic lymphoma identified using inter-specific consomic and inter-specific recombinant congenic strains of mice.

Mice of the C57BL/6J inbred strain develop thymic lymphomas at very high frequency after acute gamma-irradiation, while mice of several inbred strains derived from the wild progenitor of the Mus spretus species and their F1 hybrids with C57BL/6J appear extremely resistant. Analysis of the genetic determinism of the gamma-radiation-induced thymic lymphoma (RITL) resistance with the help of inter-specific consomic strains (ICS), which carry a single introgressed Mus spretus chromosome on a C57BL/6J genetic background, provide significant evidence for the existence of a thymic lymphoma resistance (Tlyr1) locus on chromosome 19. The subsequent analysis of the backcross progeny resulting from a cross between consomic mice heterozygous for the Mus spretus chromosome 19 and C57BL/6J mice, together with the study of inter-specific recombinant congenic strains (IRCS), suggest that this Tlyr1 locus maps within the D19Mit60-D19Mit40 chromosome interval.