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Mood alterations, anxiety, and cognitive impairments associated with adult-onset hypothyroidism often persist despite replacement treatment. In rodent models of hypothyroidism, replacement does not bring 3-iodothyronamine (T1AM) brain levels back to normal. T1AM is a thyroid hormone derivative with cognitive effects. Using a pharmacological hypothyroid mouse model, we investigated whether augmenting levothyroxine (L-T4) with T1AM improves behavioural correlates of depression, anxiety, and memory and has an effect on hippocampal neurogenesis. Hypothyroid mice showed impaired performance in the novel object recognition test as compared to euthyroid mice (discrimination index (DI): 0.02 ± 0.09 vs. 0.29 ± 0.06; t = 2.515, p = 0.02). L-T4 and L-T4+T1AM rescued memory (DI: 0.27 ± 0.08 and 0.34 ± 0.08, respectively), while T1AM had no effect (DI: −0.01 ± 0.10). Hypothyroidism reduced the number of neuroprogenitors in hippocampal neurogenic niches by 20%. L-T4 rescued the number of neuroprogenitors (mean diff = 106.9 ± 21.40, t = 4.99, pcorr = 0.003), while L-T4+T1AM produced a 30.61% rebound relative to euthyroid state (mean diff = 141.6 ± 31.91, t = 4.44, pcorr = 0.004). We performed qPCR analysis of 88 genes involved in neurotrophic signalling pathways and found an effect of treatment on the expression of Ngf, Kdr, Kit, L1cam, Ntf3, Mapk3, and Neurog2. Our data confirm that L-T4 is necessary and sufficient for recovering memory and hippocampal neurogenesis deficits associated with hypothyroidism, while we found no evidence to support the role of non-canonical TH signalling. [ABSTRACT FROM AUTHOR]

Abstract In the latest years, innovative nanomaterials have attracted a dramatic and exponentially increasing interest, in particular for their potential applications in the biomedical field. In this paper, we reported our findings on the cytocompatibility of barium titanate nanoparticles (BTNPs), an extremely interesting ceramic material. A rational and systematic study of BTNP cytocompatibility was performed, using a dispersion method based on a non-covalent binding to glycol-chitosan, which demonstrated the optimal cytocompatibility of this nanomaterial even at high concentration (100 μg/ml). Moreover, we showed that the efficiency of doxorubicin, a widely used chemotherapy drug, is highly enhanced following the complexation with BTNPs. Our results suggest that innovative ceramic nanomaterials such as BTNPs can be realistically exploited as alternative cellular nanovectors.

Featured Application: In this work, we provide a platform for nasal tissue regeneration, consisting of poly(vinyl alcohol)/gelatin sponges and mesodermal progenitor cells as a single stem cell source for connective and vascular tissues. These scaffolds show promise for application in rhinoplasty, as well as nasal tissue reconstruction following sinonasal tumor resection. Need for regeneration and repair of nasal tissues occurs as a consequence of several pathologies affecting the nose, including, but not limited to infective diseases, traumas and tumor resections. A platform for nasal tissue regeneration was set up using poly(vinyl alcohol)/gelatin sponges with 20%–30% (w/w) gelatin content to be used as scaffolds, for their intrinsic hydrophilic, cell adhesive and shape recovery properties. We propose mesodermal progenitor cells (MPCs) isolated from the bone marrow as a unique stem cell source for obtaining different connective tissues of the nose, including vascular tissue. Finally, epithelial cell immune response to these scaffolds was assessed in vitro in an environment containing inflammatory molecules. The results showed that mesenchymal stromal cells (MSCs) deriving from MPCs could be used to differentiate into cartilage and fibrous tissue; whereas, in combination with endothelial cells still deriving from MPCs, into pre-vascularized bone. Finally, the scaffold did not significantly alter the epithelial cell response to inflammatory insults derived from interaction with bacterial molecules. [ABSTRACT FROM AUTHOR]

Introduction: Connexins (Cxs) are transmembrane proteins involved in the formation of connexons/hemichannels. Two connexons of adjacent cells can dock one each other form- ing an intercellular channel at gap junction (GJ), by which ions and small metabolites can pass between cells. Single hemichannels participate in the exchange of small metabolites between cells and the extracellular space [1]. There are at least 21 isoforms of Cxs expressed in humans and they are localized in almost every tissue. More than one Cx can be expressed in each tissue and connexons can be made by a single Cx or by different types of Cxs. GJ are involved in various physiological functions including secretion in glandular tissue [2-5]. Cx26, Cx32 and Cx43 are the mainly expressed Cxs in glands, but no data are available about their expression in human salivary glands. Aim: The aim of our study is to investigate the presence and the localization of these Cxs in human minor salivary glands. Methods: human minor salivary gland biopsies (hMSGBs) were obtained as part of the routine diagnostic procedures when primary Sjögren’s Syndrome (pSS) was suspected. Samples without pSS were selected for the study. Immunofluorescence and immunoelectron microscopy were employed to evaluated Cx26, Cx32 and Cx43 protein expression while RT-PCR was used to detect their mRNA expression. Results and Conclusions: Cx expression was found at both protein and mRNA level in all hMSGBs analysed. Cxs were observed at level of the duct and acinar cell membranes, as well as in myoepithelial cells. The localization of the three Cx types was very similar, suggesting a colocalization of these Cxs in the same connexons. Further studies are necessary to confirm this hypothesis. However, these preliminary results are important because demonstrate for the first time the presence of Cxs in human salivary glands. Moreover, in the few analysed pSS samples we observed an alteration of Cx expression indicating that these proteins may be involved in salivary gland dysfunctions. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to explore the signaling pathway of Pontine (PON) in a murine model of PON-induced cardiotoxicity focusing on the involvement of Cx43, serine 368 phoshorylated Cx43 (pS368-Cx43) and Cx26 also considering sex-related differences. The study found that c onnexins are involved in mice PON-induced cardiotoxicity, showing a sex related altered expression.

Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradation, and transport drugs to the brain after crossing the blood–brain barrier. Therefore, a chitosan quaternary ammonium derivative was synthesized and conjugated with methyl-β-cyclodextrin to prepare DAL-medicated nanoparticles (DAL-NP). DAL-NP particle size was 227.7 nm, zeta potential +8.60 mV, encapsulation efficiency 89%. DAL-NP protected DAL from degradation by chymotrypsin or pancreatin and tripled DAL degradation time compared to non-encapsulated DAL. Use of DAL-NP was safe for either Caco-2 or bEnd.3 cells, with the latter selected as a blood–brain barrier model. DAL-NP could also cross either the Caco-2 or bEnd.3 monolayer by the transepithelial route. The results suggest a potential DAL-NP ability to transport to the brain a DAL dose fraction administered orally, although in vivo experiments will be needed to confirm the present data obtained in vitro. [ABSTRACT FROM AUTHOR]

The present study aimed to demonstrate that Sideral ® RM (SRM, Sucrosomial ® Raw Material Iron) is transported across the excised intestine via a biological mechanism, and to investigate the effect that this transport route may produce on oral iron absorption, which is expected to reduce the gastrointestinal (GI) side effects caused by the bioavailability of non-absorbed iron. Excised rat intestine was exposed to fluorescein isothiocyanate (FITC)-labeled SRM in Ussing chambers followed by confocal laser scanning microscopy to look for the presence of fluorescein-tagged vesicles of the FITC-labeled SRM. To identify FITC-labeled SRM internalizing cells, an immunofluorescence analysis for macrophages and M cells was performed using specific antibodies. Microscopy analysis revealed the presence of fluorescein positive particulate structures in tissues treated with FITC-labeled SRM. These structures do not disintegrate during transit, and concentrate in macrophage cells. Iron bioavailability was assessed by determining the time-course of Fe 3+ plasma levels. As references, iron contents in liver, spleen, and bone marrow were determined in healthy rats treated by gavage with SRM or ferric pyrophosphate salt (FP). SRM significantly increased both area under the curve (AUC) and clearance maxima (C max ) compared to FP, thus increasing iron bioavailability (AUC rel = 1.8). This led to increased iron availability in the bone marrow at 5 h after single dose gavage.

Background: Osteogenic growth peptide (OGP) is an endogenous tetradecapeptide present in micromolar concentrations in mammalian serum; its carboxy-terminal pentapeptide, OGP(10-14), represents its physiologically active fragment. OGP(10-14) induces proliferation and differentiation in fibroblast and osteoblast cell lines, and it enhances hematopoiesis in vitro and in vivo. The signaling pathways triggered by OGP(10-14) are not yet fully known. In the present report, we evaluated the effect of OGP(10-14) on differentiation of a cancer megakaryoblast cell line and its involvement on RhoA and Src family kinases signaling pathway., Material/methods: Cell proliferation of the Mo-7e line was evaluated using the MTT test. Mo-7e differentiation was evaluated by microscopic observation of cell morphology and by expression of the factor VIII-related antigen. Involvement of RhoA and Src kinases on signaling pathways triggered by OGP(10-14) was analyzed using RhoA and Src family kinase (SFK) inhibitors (C3 and PP2) and an immunoperoxidase technique., Results: OGP(10-14) induces expression of the factor VIII-related antigen, morphologic changes indicative of megakaryocytic differentiation, and a down-regulation of the Fyn Src kinase. These OGP(10-14) effects were prevented by C3 and enhanced by PP2., Conclusions: The anti-proliferative and pro-differentiating activities of OGP(10-14) on thrombopoietin (TPO)-primed Mo-7e cells are mediated by RhoA and Src kinase pathways as demonstrated by the use of C3 and PP2.