Thurstonogden7516

Niemann-Pick Disease type B (NPDB) is a rare autosomal recessive disease belonging to the family of lysosomal storage disorders. NPDB is caused by mutations of sphingomyelin phosphodiesterase 1 gene (SMPD1) and is characterized by hepatosplenomegaly, interstitial lung disease, recurrent pulmonary infections, and neurologic disorders. Bronchiectasis are atypical. Until now, only three cases of lung transplantation for severe respiratory impairment have been reported. We describe a case of NPDB that was diagnosed after lung transplantation for cystic bronchiectasis. In 2016, a 31-year-old woman who was experiencing hypoxemic respiratory failure and recurrent pulmonary infections due to cystic bronchiectasis received a double-lung-transplantation. Histopathologic study on removed lungs revealed clusters of CD68 foamy lipid-laden macrophages with concentric and palisade arrangement, compatible with the diagnosis of NPDB, which was confirmed after SMPD1 genetic sequencing. Twenty-three months after transplantation, allograft function is stable (FEV1 was 100% of best-FEV1). The singularity of this case lies in the presence of bronchiectasis, which is an unprecedently described phenotype of NPDB. This finding was accompanied by the detection of a novel SMPD1 mutation (p.Ala46=) of uncertain meaning.The development of treatment strategies for improving secondary stability at the bone-implant interface is a challenge. Porous implants are one solution for improving long-term implant stability, but the osteoconduction process of implants into the bone can be slow. Strain-driven osteogenesis from the mechanostat theory offers insight into pathways for post-operative treatment but mechanisms to deliver strain to the bone-implant interface need refinement. In this work, the use of therapeutic ultrasound is simulated to induce resonance into a porous implant structure. Local strains through the scaffold are measured by varying systemic variables such as damping ratio, applied vibrational force, primary bone-implant stability, and input frequency. At the natural frequency of the system with applied forces of 0.5 N and a damping ratio of 0.5%, roughly half of the nodes in the simulated environment exceed the microstrain threshold of 1000 με required for new bone formation. A high degree of sensitivity was noted upon changing input frequency, with minor sensitivities arising from damping ratio and applied vibrational force. These findings suggest that the application of therapeutic resonance to improve osseointegration of the bone-implant interface may be viable for applications including dental implants or segmental bone defects.Magnesium is the fourth most abundant element in the human body with a wide battery of functions in the maintenance of normal cell homeostasis. In the bone, this element incorporates in the hydroxyapatite structure and it takes part in mineral metabolism and regulates osteoclast functions. In this study, sol-gel materials with increasing concentrations of MgCl2 (0.5, 1, and 1.5%) were synthesized and applied onto Ti surfaces as coatings. The materials were first physicochemically characterized. In vitro responses were examined using the MC3T3-E1 osteoblastic cells and RAW264.7 macrophages. Human serum protein adsorption was evaluated employing nLC-MS/MS. The incorporation of Mg did not affect the crosslinking of the sol-gel network, and a controlled release of Mg was observed; it was not cytotoxic at any of the tested concentrations. The cytoskeleton arrangement of MC3T3-E1 cells cultured on the Mg-doped materials changed in comparison with controls; the cells became more elongated, with protruded lamellipodia and increased cell surface. The expression of integrins (ITGA5 and ITGB1) was boosted by Mg-coatings. The ALP activity and expression of TGF-β, OSX and RUNX2 genes were also increased. In RAW264.7 cells, TNF-α secretion was reduced, while TGF-β and IL-4 expression rose. selleckchem These changes correlated with the altered protein adsorption patterns. The Mg-doped coatings showed increased adsorption of anti-inflammatory (CLUS, IC1, CFAH, and VTNC), cell adhesion (DSG1, FILA2, and DESP) and tissue regeneration (VTNC and CYTA) proteins. This integrated approach to biomaterial characterization revealed the potential of Mg in bone tissue regeneration.Novel linear cationic poly(amide aminotriazole)s (PATnD) with secondary amine groups in the backbone were obtained by using azide-alkyne 1,3-dipolar cycloaddition reactions metal- and solvent-free (thermal conditions, PATTnD) or copper(I)-catalyzed (Sharpless conditions, PATCnD). PATnD were investigated in vitro against strains of E. coli, P. aeruginosa, S. link2 aureus, and S. epidermidis. Hemolytic activity was tested using human red blood cells (hRBC), and very low or no hemolytic activity was observed. The cytotoxicity of PATnD polymers against Human Gingival Fibroblasts (HGnF) cells was concentration-dependent, and significant differences between PATT1D and PATC1D were observed. The ability of these polymers to induce resistance against both Gram-positive and Gram-negative bacteria was also assessed. Studied bacterial strains acquired resistance to catalytic polymers (PATCnD) in initial passages meanwhile resistance to thermal polymers (PATTnD) appears in later passages, being the increase of the minimum inhibitory concentration lower than in catalytic polymers. This result, together with the higher biocidal capacity of thermal polymers compared to catalytic ones, seems to suggest an influence of the regiospecificity of the polymers on their antibacterial characteristics. This study also demonstrates that PAT1D polymers, which do not appear to have strong hydrophobic residues, can exert significant antimicrobial activity against Gram-positive bacteria such as S. epidermidis. This pair of polymers, PATC1D and PATT1D, displays the greatest antimicrobial activity while not causing significant hemolysis along with the lowest susceptibility for resistance development of the polymers evaluated.An experimental model of pressure-induced optic nerve damage promises to greatly expand understanding of the cellular events leading to retinal ganglion cell (RGC) death and of how they are influenced by intraocular pressure (IOP) and other risk factors associated with glaucoma. In this work, we propose a novel strategy employing photo-crosslinkable azidobenzoic acid-modified chitosan (Az-CH) for long-term, persistent elevation of IOP. For this purpose, a solution of Az-CH was injected into the anterior chamber of experimental rat eyes, which were subsequently irradiated with ultraviolet (UV) light to form an Az-CH gel that hindered aqueous outflow and effected prolonged IOP elevation thereby. The control eyes were treated as follows (1) intracameral injection of Az-CH without UV irradiation, (2) intracameral injection of saline solution without UV irradiation or (3) no injection with UV irradiation. A significant IOP increase was observed in the experimental eyes, which was continuously higher for the whole testing period of 12 weeks after one-time treatment with Az-CH injection and UV irradiation. Also, a more significant loss of RGCs, one of the major features of glaucoma, was observed in experimental eyes than in the control eyes. Therefore, the strategy presented herein can be a novel experimental model to study the mechanism of RGC damage by elevated IOP over the course of a prolonged period.Bacterial infection is a common phenomenon in the process of postoperative wound healing. In severe cases, it may even lead to life-threatening, which brings a heavy burden to the clinical treatment and causes huge losses to the society and economy. As one of the most commonly applied medical materials for wound treatment, hydrogel dressings are mainly used to cover and protect wounds and provide a favorable environment to facilitate wound healing. In this work, we developed an antibacterial hydrogel dressing (Fc-PAAM) with high adhesion, which is consisted of polyacrylamide (PAM) hydrogel framework and polyacrylic acid-functionalized (PAA) with ferrocene (Fc). Morphology, adhesion and pressure resistance of PAAM hydrogel were confirmed by using scanning electron microscope (SEM) and universal testing machine, and Fc decoration in the hydrogel network was well demonstrated by using Fourier transform infrared spectroscopy (FT-IR). Ultraviolet-visible spectroscopy (UV-vis) displayed that the Fc-PAAM hydrogel had excellent peroxidase-like activity as well. It not only exhibited prominent antimicrobial activity against Gram (+/-) bacteria, but also performed high efficiency in preventing the formation of biofilms. In addition, in vivo experiments indicated that this adhesive dressing could significantly prevent bacterial infections. Compared with other clinical treatment methods, this kind of hydrogel is not easy to cause bacterial resistance, and the used raw materials are easy to obtain and low in price, which can amplify the antibacterial properties of H2O2 and provide a new opportunity for the treatment of clinical bacterial infections.Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e., non-responsive to biological cues. However, tissue remodeling necessary for implant integration features an ever-changing milieu of cells that demands a responsive biomaterial surface for temporal synchronization of interactions between biomaterial and tissue. Here, we successfully synthesized a multi-functional, dynamic coating on titanium by co-immobilizing GL13K antimicrobial peptide and an MMP-9 - a matrix metalloproteinase secreted by bone-remodeling osteoclasts - responsive peptide. Our co-immobilized peptide surface showed potent anti-biofilm activity, enabled effective osteoblast and fibroblast proliferation, and demonstrated stability against a mechanical challenge. Finally, we showed peptide release was triggered for up to seven days when the multi-peptide coatings were cultured with MMP-9-secreting osteoclasts. Our MMP-9 cleavable peptide can be conjugated with osteogenic or immunomodulatory motifs for enhanced bone formation in future work. Overall, we envisage our multifunctional, dynamic surface to reduce infection rates of percutaneous bone-anchored devices via strong anti-microbial activity and enhanced tissue regeneration via temporal synchronization between biomaterial cues and tissue responses.Many approaches and technologies have been developed as treatments for microsporidian, infections but effective, broad-spectrum, and sustainable therapeutic approaches have not been found. Silver nanoparticles (AgNPs) have antimicrobial activity and are widely used against many different pathogens. AgNPs provide an opportunity to develop formulations that will control microsporidia. In this study, we synthesized AgNPs via a chemical reduction method and evaluated their formation, morphology, and stability using transmission electron microscopy (TEM) and ultraviolet spectroscopy analysis. We verified that AgNPs could disrupt the spore cell membrane and spore germination of microsporidia Nosema bombycis. This resulted in the release of microsporidia nucleic acids, proteins, and respiratory chain enzymes. link3 The anti-microsporidia activity of AgNPs was studied by measuring the silkworm larvae survival rate and spore genome replication after microsporidia infection. AgNPs have anti-microsporidian activity and could be effective components of formulations for treating or preventing microsporidia infection.