Resorbable membrane design: In vitro characterization of silver doped-hydroxyapatite-reinforced XG/PEI semi-IPN composite.

In this study, the production and characterization of silver-doped hydroxyapatite (AgHA) reinforced Xanthan gum (XG) and Polyethyleneimine (PEI) reinforced semi-interpenetrating polymer network (IPN) biocomposite, known to be used as bone cover material for therapeutic purposes in bone tissue, were performed. XG/PEI IPN films containing 2AgHA nanoparticles were produced by simultaneous condensation and ionic gelation. Characteristics of 2AgHA-XG/PEI nanocomposite film were evaluated by structural, morphological (SEM, XRD, FT-IR, TGA, TM, and Raman) and biological activity analysis (degradation, MTT, genotoxicity, and antimicrobial activity) techniques.

Analysis of the T-cell repertoire and transcriptome identifies mechanisms of regulatory T-cell suppression of GVHD.

CD4+FOXP3+ regulatory T cells (Tregs) have demonstrated efficacy in the prevention and treatment of graft-versus-host disease (GVHD). Preclinical and clinical studies indicate that Tregs are able to protect from GVHD without interfering with the graft-versus-tumor (GVT) effect of hematopoietic cell transplantation (HCT), although the underlying molecular mechanisms are largely unknown. To elucidate Treg suppressive function during in vivo suppression of acute GVHD, we performed paired T-cell receptor (TCRα and ΤCRβ genes) repertoire sequencing and RNA sequencing analysis on conventional T cells (Tcons) and Tregs before and after transplantation in a major histocompatibility complex -mismatched mouse model of HCT.

Fabrication of mechanically advanced polydopamine decorated hydroxyapatite/polyvinyl alcohol bio-composite for biomedical applications: In-vitro physicochemical and biological evaluation.

In this study, polydopamine (PDA) coated hydroxyapatite (HA) reinforced polyvinyl alcohol (PVA) films were produced to be used in biomedical applications such as bone tissue regeneration. pDA is coated not only to prevent the agglomeration of HA when encountering interstitial fluids but also to strongly bind the PVA for the interaction between materials so that the mechanical performance becomes more stabilized. pDA was coated on the hydroxyapatite surface using a radical polymerization technique, and the reinforced PVA were produced with pDA-coated HA (pDA-HA/PVA) nanoparticles.

Evolution of dynamics of physico-chemical and mechanical properties of hydroxyapatite with fluorine addition and degradation stability of new matrices.

This multidisciplinary study examined sensitively the change in the dynamics of main mechanical performance, stability of crystal structure, crystallinity quality, strength, corrosion resistance, biocompatibility, resistance to structural degradation/separations and mechanical durability features of hydroxyapatite (HAp) biomedical materials based on the fluorine addition and degradation process to guide future medical and dental treatment studies. In the study, the fluorine ions were used to be the dental coating, filling and supporting material for biologically or synthetically produced bone minerals. The general characteristic properties were investigated by means of standard spectroscopic, structural and mechanical analysis methods including RAMAN, SEM-EDS, TEM, Vickers micro-indentation hardness and density measurements.

Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma.

Background: Glypican-3 (GPC-3) is an oncofetal protein that is highly expressed in various solid tumors, but rarely expressed in healthy adult tissues and represents a rational target of particular relevance in hepatocellular carcinoma (HCC). Autologous chimeric antigen receptor (CAR) αβ T cell therapies have established significant clinical benefit in hematologic malignancies, although efficacy in solid tumors has been limited due to several challenges including T cell homing, target antigen heterogeneity, and immunosuppressive tumor microenvironments. Gamma delta (γδ) T cells are highly cytolytic effectors that can recognize and kill tumor cells through major histocompatibility complex (MHC)-independent antigens upregulated under stress.

La and F dual-doped multifunctional hydroxyapatite nanoparticles: Synthesis and characterization.

Hydroxyapatite (HA) co-doped with La and F ions were synthesized by the precipitation method and sintered at 1,100°C for 1 hr. Samples were characterized by the standard experimental methods including the density, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) to investigate their microstructure, phase formation, and bonding characteristics in detail. Moreover, the materials produced were identified using the microhardness tests.

Activation of natural killer T cells enhances the function of regulatory T-cell therapy in suppressing murine GVHD.

Cellular therapy with regulatory T cells (Tregs) has shown promising results for suppressing graft-versus-host disease (GVHD) while preserving graft vs tumor effects in animal models and phase 1/2 clinical trials. However, a paucity of Tregs in the peripheral blood makes it difficult to acquire sufficient numbers of cells and hampers further clinical application. Invariant natural killer T (iNKT) cells constitute another compartment of regulatory cells that ameliorate GVHD through activation of Tregs after their own activation with α-galactosylceramide (α-GalCer) or adoptive transfer.

Activation of the DR3-TL1A Axis in Donor Mice Leads to Regulatory T Cell Expansion and Activation With Reduction in Graft-Versus-Host Disease.

Death receptor 3 (DR3) is a tumor necrosis factor receptor superfamily member (TNFRSF25), which is minimally expressed on resting conventional T cells (though readily inducible upon cell activation), yet highly expressed on resting FoxP3 regulatory T cells (Treg). We recently demonstrated that activation of DR3 with an agonistic antibody (4C12) leads to selective expansion and activation of Treg in healthy mice and suppression of graft-versus-host disease (GVHD) in recipient mice when donor mice are treated. However, given the long antibody half-life and concomitant safety concerns, along with the lack of a humanized agonistic antibody to DR3, both human and murine fusion proteins incorporating the natural DR3 ligand TL1A (TL1A-Ig) have been developed.

Silver release of Ag (I) doped hydroxyapatite: In vitro study.

A material is produced by doping of silver (Ag (I)) which has antibacterial property to nano hydroxyapatite (nHAp), to remove the hipersensitivity in the teeth by closing the dentine tubules or dental micro cracks of the teeth and effective against for some bacteria. The doping of Ag (I) can also produces a toxic effect. Ag (I) can be released from the structure as a result of biological, physical and chemical effects and may cause toxicity.

Dentinal tubule occluding capability of nano-hydroxyapatite; The in-vitro evaluation.

In this in-vitro study, the effectiveness of experimental pure nano-hydroxyapatite (nHAP) and 1%, 2%, and 3% F¯ doped nano-HAp on dentine tubule occlusion was investigated. And also, the cytotoxicity of materials used in the experiment was evaluated. Nano-HAp types were synthesized by the precipitation method.

The Notch Intracellular Domain Has an RBPj-Independent Role during Mouse Hair Follicular Development.

Ligand-dependent activation, γ-secretase-processed cleavage, and recombining binding protein Jk (RBPj)-mediated downstream transcriptional activities of Notch receptors constitute the "canonical" Notch signaling pathway, which is essential for skin organogenesis. However, in Msx2-Cre mice, keratinocyte-specific deletion of the Rbpj gene in utero produced a significantly milder phenotype than either global Notch or γ-secretase loss. Herein, we investigated the underlying mechanisms for this apparent noncanonical signal using mouse genetics.

Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity.

We have previously described the creation and analysis of a Notch1 activity-trap mouse line, Notch1 intramembrane proteolysis-Cre6MT or N1IP::Cre(LO), that marked cells experiencing relatively high levels of Notch1 activation. Here, we report and characterize a second line with improved sensitivity (N1IP::Cre(HI)) to mark cells experiencing lower levels of Notch1 activation. This improvement was achieved by increasing transcript stability and by restoring the native carboxy terminus of Cre, resulting in a five- to tenfold increase in Cre activity.

Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens.

Defense against attaching-and-effacing bacteria requires the sequential generation of interleukin 23 (IL-23) and IL-22 to induce protective mucosal responses. Although CD4(+) and NKp46(+) innate lymphoid cells (ILCs) are the critical source of IL-22 during infection, the precise source of IL-23 is unclear. We used genetic techniques to deplete mice of specific subsets of classical dendritic cells (cDCs) and analyzed immunity to the attaching-and-effacing pathogen Citrobacter rodentium.

The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation.

Evidence is accumulating to suggest that our indigenous microbial communities (microbiota) may have a role in modulating allergic and immune disorders of the skin. To examine the link between the microbiota and atopic dermatitis (AD), we examined a mouse model of defective cutaneous barrier function with an AD-like disease due to loss of Notch signaling. Comparisons of conventionally raised and germ-free (GF) mice revealed a similar degree of allergic skin inflammation, systemic atopy, and airway hypersensitivity.

Loss of RBPj in postnatal excitatory neurons does not cause neurodegeneration or memory impairments in aged mice.

Previous studies suggest that loss of γ-secretase activity in postnatal mouse brains causes age-dependent memory impairment and neurodegeneration. Due to the diverse array of γ-secretase substrates, it remains to be demonstrated whether loss of cleavage of any specific substrate(s) is responsible for these defects. The bulk of the phenotypes observed in mammals deficient for γ-secretase or exposed to γ-secretase inhibitors are caused by the loss of Notch receptor proteolysis.

Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin.

Thymic Stromal Lymphopoietin (TSLP), a cytokine implicated in induction of T helper 2 (Th2)-mediated allergic inflammation, has recently been shown to stimulate solid tumor growth and metastasis. Conversely, studying mice with clonal loss of Notch signaling in their skin revealed that high levels of TSLP released by barrier-defective skin caused a severe inflammation, resulting in gradual elimination of Notch-deficient epidermal clones and resistance to skin tumorigenesis. We found CD4(+) T cells to be both required and sufficient to mediate these effects of TSLP.

Variation in the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine.

S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory infection by decreasing the attachment of respiratory pathogens to human pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of respiratory infections. A previous study revealed that treatment of S.

Cellular localization and stimulation-associated distribution dynamics of syntaxin-1 and syntaxin-3 in gastric parietal cells.

Syntaxins are differentially localized in polarized cells and play an important role in vesicle trafficking and membrane fusion. These soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are believed to be involved in tubulovesicle trafficking and membrane fusion during the secretory cycle of the gastric parietal cell. We examined the cellular localization and distribution of syntaxin-1 and syntaxin-3 in rabbit parietal cells.

Class I major histocompatibility complex presentation of antigens that escape from the parasitophorous vacuole of Toxoplasma gondii.

The intracellular parasite Toxoplasma gondii, the causative agent of toxoplasmosis, induces a protective CD8 T-cell response in its host; however, the mechanisms by which T. gondii proteins are presented by the class I major histocompatibility complex remain largely unexplored. T.

S-carboxymethylcysteine inhibits the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells.

Streptococcus pneumoniae causes respiratory and other invasive infections. Increased resistance of this bacterium to antibiotics necessitates new approaches to the treatment of infections. Attachment of bacteria to human pharyngeal epithelial cells is the initial step in the pathogenesis of infection and S-carboxymethylcysteine (S-CMC) can modulate the attachment of Moraxella catarrhalis and nontypable Haemophilus influenzae to epithelial cells.