3,467 research outputs found

    Synthesis, Drug Release, and Antibacterial Properties of Novel Dendritic CHX-SrCl2 and CHX-ZnCl2 Particles

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    This work demonstrated for the first time the synthesis of novel chlorhexidine particles containing strontium and zinc, to provide an effective, affordable, and safe intervention in the treatment of recurrent infections found in Medicine and Dentistry. The CHX-SrCl2 and CHX-ZnCl2 particles were synthesized by co-precipitation of chlorhexidine diacetate (CHXD) and zinc chloride or strontium chloride, where particle size was manipulated by controlling processing time and temperature. The CHX-ZnCl2 and CHX-SrCl2 particles were characterized using SEM, FTIR, and XRD. UV-Vis using artificial saliva (pH 4 and pH 7) was used to measure the drug release and ICP-OES ion release. The antibacterial properties were examined against P. gingivalis, A. actinomycetemcomitans, and F. nucleatum subsp. Polymorphum, and cytotoxicity was evaluated using mouse fibroblast L929 cells. The novel particles were as safe as commercial CHXD, with antibacterial activity against a range of oral pathogens. UV-Vis results run in artificial saliva (pH 4 and pH 7) indicated a higher release rate in acidic rather than neutral conditions. The CHX-ZnCl2 particles provided the functionality of a smart Zinc and CHX release, with respect to environmental pH, allowing responsive antibacterial applications in the field of medicine and dentistry

    Administration of defined microbiota is protective in a murine Salmonella infection model.

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    Salmonella typhimurium is a major cause of diarrhea and causes significant morbidity and mortality worldwide, and perturbations of the gut microbiota are known to increase susceptibility to enteric infections. The purpose of this study was to investigate whether a Microbial Ecosystem Therapeutic (MET-1) consisting of 33 bacterial strains, isolated from human stool and previously used to cure patients with recurrent Clostridium difficile infection, could also protect against S. typhimurium disease. C57BL/6 mice were pretreated with streptomycin prior to receiving MET-1 or control, then gavaged with S. typhimurium. Weight loss, serum cytokine levels, and S. typhimurium splenic translocation were measured. NF-κB nuclear staining, neutrophil accumulation, and localization of tight junction proteins (claudin-1, ZO-1) were visualized by immunofluorescence. Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum. MET-1 also preserved cecum tight junction protein expression, and reduced S. typhimurium translocation to the spleen. Notably, MET-1 did not decrease CFUs of Salmonella in the intestine. MET-1 may attenuate systemic infection by preserving tight junctions, thereby inhibiting S. typhimurium from gaining access to the systemic circulation. We conclude that MET-1 may be protective against enteric infections besides C. difficile infection

    Biochemical systems identification by a random drift particle swarm optimization approach

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    BACKGROUND: Finding an efficient method to solve the parameter estimation problem (inverse problem) for nonlinear biochemical dynamical systems could help promote the functional understanding at the system level for signalling pathways. The problem is stated as a data-driven nonlinear regression problem, which is converted into a nonlinear programming problem with many nonlinear differential and algebraic constraints. Due to the typical ill conditioning and multimodality nature of the problem, it is in general difficult for gradient-based local optimization methods to obtain satisfactory solutions. To surmount this limitation, many stochastic optimization methods have been employed to find the global solution of the problem. RESULTS: This paper presents an effective search strategy for a particle swarm optimization (PSO) algorithm that enhances the ability of the algorithm for estimating the parameters of complex dynamic biochemical pathways. The proposed algorithm is a new variant of random drift particle swarm optimization (RDPSO), which is used to solve the above mentioned inverse problem and compared with other well known stochastic optimization methods. Two case studies on estimating the parameters of two nonlinear biochemical dynamic models have been taken as benchmarks, under both the noise-free and noisy simulation data scenarios. CONCLUSIONS: The experimental results show that the novel variant of RDPSO algorithm is able to successfully solve the problem and obtain solutions of better quality than other global optimization methods used for finding the solution to the inverse problems in this study

    Origination of New Immunological Functions in the Costimulatory Molecule B7-H3: The Role of Exon Duplication in Evolution of the Immune System

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    B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-γ production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses

    A physical organogel electrolyte: Characterized by in situ thermo-irreversible gelation and single-ion-predominent conduction

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    Electrolytes are characterized by their ionic conductivity (??i). It is desirable that overall ??i results from the dominant contribution of the ions of interest (e.g. Li+ in lithium ion batteries or LIB). However, high values of cationic transference number (t+) achieved by solid or gel electrolytes have resulted in low ??i leading to inferior cell performances. Here we present an organogel polymer electrolyte characterized by a high liquid-electrolyte- level ??i (???101 mS cm-1) with high t+ of Li+ (>0.8) for LIB. A conventional liquid electrolyte in presence of a cyano resin was physically and irreversibly gelated at 60 ??C without any initiators and crosslinkers, showing the behavior of lower critical solution temperature. During gelation, ??i of the electrolyte followed a typical Arrhenius-type temperature dependency, even if its viscosity increased dramatically with temperature. Based on the Li + -driven ion conduction, LIB using the organogel electrolyte delivered significantly enhanced cyclability and thermal stability.open5

    China’s Weibo: is faster different?

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    The popularization of microblogging in China represents a new challenge to the state’s regime of information control. The speed with which information is diffused in the microblogosphere has helped netizens to publicize and express their discontent with the negative consequences of economic growth, income inequalities and official corruption. In some cases, netizen led initiatives have facilitated the mobilization of online public opinion and forced the central government to intervene to redress acts of lower level malfeasance. However, despite the growing corpus of such cases, the government has quickly adapted to the changing internet ecology and is using the same tools to help it maintain control of society by enhancing its claims to legitimacy, circumscribing dissent, identifying malfeasance in its agents and using online public opinion to adapt policy and direct propaganda efforts. This essay reflects on microblogging in the context of the Chinese internet, and argues that successes in breaking scandals and mobilizing opinion against recalcitrant officials should not mask the reality that the government is utilizing the microblogosphere to its own advantage

    Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

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    The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

    In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

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    Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses
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