Search

Silver nanoparticles were prepared on chitin nanofiber surfaces by UV light reduction of silver ions. The chitin nanofibers could be efficient substrates to immobilize silver nanoparticles with stable dispersion states. The dispersion and the nanocomposite film with acrylic resin showed characteristic absorption property in the visible light region due to the effect of the silver nanoparticles. Silver nanoparticles endowed strong antifungal activity to chitin nanofibers. [ABSTRACT FROM AUTHOR]

Novel biological adhesives made from chitin derivatives were prepared and evaluated for their adhesive properties and biocompatibility. Chitin derivatives with acrylic groups, such as 2-hydroxy-3-methacryloyloxypropylated carboxymethyl chitin (HMA-CM-chitin), were synthesized and cured by the addition of an aqueous hydrogen peroxide solution as a radical initiator. The adhesive strength of HMA-CM-chitin increased when it was blended with chitin nanofibers (CNFs) or surface-deacetylated chitin nanofibers (S-DACNFs). HMA-CM-chitin/CNFs or HMA-CM-chitin/S-DACNFs have almost equal adhesive strength compared to that of a commercial cyanoacrylate adhesive. Moreover, quick adhesion and induction of inflammatory cells migration were observed in HMA-CM-chitin/CNF and HMA-CM-chitin/S-DACNF. These findings indicate that the composites prepared in this study are promising materials as new biological adhesives. [ABSTRACT FROM AUTHOR]

Chitosan nanofibers were easily prepared from fully deacetylated chitosan dry powder using a high-pressure waterjet system. From SEM observation, after 10 cycles of treatment, most of the chitosan had been reduced to homogeneous nanofibers measuring tens of nanometers. On the other hand, further mechanical treatment did not show a significant change. Relative crystallinity of chitosan nanofibers gradually decreased as the number of passes increased since high-pressure waterjet treatment damaged the crystalline region of chitosan nanofibers. The transmittance of the chitosan nanofiber slurry increased steeply, as the number of passes increased, indicating that the chitosan fibers were disintegrated effectively. Viscosity of chitosan nanofiber slurry also showed that the chitosan disintegrated well into nanofibers up to 10 passes. Above 10 passes, disintegration efficiency was saturated. The molecular weights of the nanofibers steeply decreased due to the depolymerization of chitosan by mechanical disintegration. The Young's modulus and tensile strength of chitosan nanofiber sheets were improved as the number of treatments increased, but further treatments deteriorated the tensile strength. [ABSTRACT FROM AUTHOR]

Highlights: [•] A unique xanthan gum (Xan) hydrogel was subjected to an alternate soaking process. [•] Hydroxyapatite (Hap) was mineralized upon the Xan-matrix surface by the process. [•] The mineralization induced a microstructure change in the gel-matrix. [•] The resulting Hap–Xan composite hydrogel showed good mechanical property. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chitin nanofiber films plasticized with glycerol were prepared. [•] Mechanical properties of the films were controlled due to plasticizing effect. [•] Glycerol did not change the high transparency of the nanofiber film. [•] Glycerol did not change the low thermal expansion of the nanofiber film. [ABSTRACT FROM AUTHOR]

Highlights: [•] The application of nanofibrils and nanocrystals to skin preserves the structure of the skin. [•] pH of nanofibrils and nanocrystals is an important criterion for topical formulations. [•] The application of nanofibrils and nanocrystals reduce production of TGF-β. [ABSTRACT FROM AUTHOR]

Highlights: [•] Fucoidan and chondroitin sulfate were depolymerized under hydrothermal conditions. [•] The molecular weight is controlled by the reaction temperature and time. [•] Under mild conditions, desulfation and deformation does not occur. [•] The hydrothermal treatment is applicable to various sulfated polysaccharides. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chitin nanofiber reinforced chitosan films were prepared. [•] The nano-composite films were highly transparent. [•] Mechanical properties of chitosan films were improved. [•] Thermal expansion of chitosan film was significantly decreased. [•] The nano-composite films showed antifungal activity. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chitosan nanofibers were easily prepared by Star Burst system. [•] Chitosan nanofibers were characterized in detail. [•] As the number of passes increased, the nanofibers became thinner. [•] Mechanical properties of the nanofiber sheet were improved up to 10 passes. [•] Chitosan nanofibers could be dispersed homogeneously in neutral water. [ABSTRACT FROM AUTHOR]

In addition to haem copper oxidases, all higher plants, some algae, yeasts, molds, metazoans, and pathogenic microorganisms such as Trypanosoma brucei contain an additional terminal oxidase, the cyanide-insensitive alternative oxidase (AOX). AOX is a diiron carboxylate protein that catalyzes the four-electron reduction of dioxygen to water by ubiquinol. In T. brucei, a parasite that causes human African sleeping sickness, AOX plays a critical role in the survival of the parasite in its bloodstream form. Because AOX is absent from mammals, this protein represents a unique and promising therapeutic target. Despite its bioenergetic and medical importance, however, structural features of any AOX are yet to be elucidated. Here we report crystal structures of the trypanosomal alternative oxidase in the absence and presence of ascofuranone derivatives. All structures reveal that the oxidase is a homodimer with the nonhaem diiron carboxylate active site buried within a four-helix bundle. Unusually, the active site is ligated solely by four glutamate residues in its oxidized inhibitor-free state; however, inhibitor binding induces the ligation of a histidine residue. A highly conserved Tyr220 is within 4 Å of the active site and is critical for catalytic activity. All structures also reveal that there are two hydrophobic cavities per monomer. Both inhibitors bind to one cavity within 4 Å and 5 Å of the active site and Tyr220, respectively. A second cavity interacts with the inhibitor-binding cavity at the diiron center. We suggest that both cavities bind ubiquinol and along with Tyr220 are required for the catalytic cycle for O2 reduction. [ABSTRACT FROM AUTHOR]

Abstract: A one-pot synthesis was used to produce chitosan derivatives with polyphenolic side chains via a regioselective phenolic coupling reaction. Under Mannich reaction conditions, treatment of chitosan with formaldehyde and methyl 2,4-dihydroxybenzoate gave N-(2,6-dihydroxy-3-methoxycarbonylphenyl)methylated chitosan in good yield (87%). Formation of a Ccurred regioselectively at the C(3) position of methyl 2,4-dihydroxybenzoate. Chitosan derivatives having various phenolic compounds as a side chain were easily synthesized in a similar manner. The chitosan derivatives showed good biodegradability and improved their solubility in methanol (9.8mgmL−1) and 2-methoxyethanol (> 10mgmL−1). The UV protection provided by the derivatives with phenolic benzophenone side chain was evaluated using UV spectra of polyethylene terephthalate and poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) films coated with the derivatives and the derivatives absorbed effectively in the UV-A region (<60%). Self-aggregation of the chitosan derivatives with the phenolic side chain was observed by using a fluorescent probe in aqueous solution. [Copyright &y& Elsevier]

Abstract: A short synthesis of chemoselective chitosan derivatives was achieved by copper-catalyzed Huisgen cycloaddition, which is an ideal reaction for click chemistry, by using N-(4-azidophthaloyl)-chitosan. N-(4-azidophthaloyl)-chitosan was prepared through chemoselective N-bromophthaloylation of chitosan in acidic water and subsequent azidation. The obtained N-(4-bromopthaloyl)-chitosan had higher solubility in common solvents than conventional phthaloyl chitosan. N-(4-azidophthaloyl)-chitosan was successfully converted with ethynyl derivatives having functional groups (hydroxymethyl, phenyl, and methyl ester) in the presence of copper(II) sulfate, sodium ascorbate and/or trimethylamine. FT-IR spectra, elemental analyses, and 1H and 13C NMR spectra supported that the desired chitosan derivatives were chemoselectively transferred by these groups with a 1,4-triazole linker. [Copyright &y& Elsevier]

Chitin nanofibers (CNFs)- nanoparticles ( NPs) blends in dispersion, flakes and thin film or sheet forms were first prepared by mixing pre-organized NPs prepared in triblock copolymer with diluted CNFs suspension. Water soluble polymer triblock copolymer poly (methyl vinyl ether, PMVE) in the amount 0.6 wt.% was used to prepare NPs and 0.12 wt.% net chitin content was used as CNFs suspension to prepare the blended composite. NPs of size 4.4 nm (σ = 1.2) were obtained when salt ( (hydrogen tetrachloroaurate (III) trihydrate) was reduced by 5 equivalents of . PMVE polymer acted as a stabilizing or capping agent for pre-organized NPs. Completion of reaction was fast, all salt reduced to metallic form in just 15 min after the addition of . CNFs (1 wt.% chitin) which was used to prepare CNFs- NPs blend composite were prepared from crab shell in never dried acidic condition by established combination of chemical and mechanical processes that gave 25-40 nm width and high aspect ratio CNFs. When polymer capped NPs mixed with CNF suspension, all NPs and 56% polymer were mass transferred from water phase to entangle with more polar moieties of CNFs-water suspension as no trace of NPs were noticed in water-polymer mother liquor after blending with CNFs suspension. Particles size of CNFs- NPs composite was measured by employing TEM, SAXS and SEM techniques. CNFs- NPs composite were characterized in solution and compressed dried sheet form by recording digital images, UV-vis and XRD spectroscopies. CNFs- NPs suspension had antibacterial activity against gram positive bacteria S. aureus. [ABSTRACT FROM AUTHOR]

Abstract: Graft copolymerization of acrylic acid (AA) on chitin nanofibers was carried out with potassium persulfate as a free radical initiator in an aqueous medium. The molar ratio of grafted AA increased with the AA concentration. The grafted chitin nanofibers were characterized by FT-IR, FE-SEM, UV–vis, XRD, and TGA. After polymerization, the characteristic morphology of chitin nanofibers was maintained. Chitin nanofibers grafted with AA were efficiently dissociated and dispersed homogeneously in basic water because of the electrostatic repulsion effect between nanofibers. AA was grafted on the surface and amorphous part of chitin nanofibers, and the original crystalline structure of α-chitin was maintained. At 330°C, the weight residue of the graft copolymer increased with the grafted AA content. [Copyright &y& Elsevier]

Abstract: We evaluated the anti-inflammatory and anti-fibrosis effects of α-chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC). α-Chitin nanofibrils decreased positive areas of nuclear factor-κB staining in the colon tissue (7.2±0.5%/fields in the α-chitin nanofibrils group vs. 10.7±0.9%/fields in the control group; p <0.05). α-Chitin nanofibrils also decreased serum monocyte chemotactic protein-1 concentration in DSS-induced acute UC (24.1±7.8pg/ml in the α-chitin nanofibrils group vs. 53.5±3.1pg/ml in the control group; p <0.05). Moreover, α-chitin nanofibrils suppressed the increased positive areas of Masson''s trichrome staining in colon tissue (6.8±0.6%/fields in the α-chitin nanofibrils group vs. 10.1±0.7%/fields in the control group; p <0.05). On the other hand, α-chitin powder suspension did not show these effects in DSS-induced acute UC mice model. Our results indicated that α-chitin nanofibrils have the anti-inflammatory effect via suppressing NF-κB activation and the anti-fibrosis effects in DSS-induced acute UC mice model. [Copyright &y& Elsevier]

Abstract: Chitin nanofibers (CNFs) reinforced silsesquioxane-urethaneacrylate (SSQ-UA) copolymer films were prepared. CNFs-SSQ-UA nanocomposite films were highly transparent due to the filling of nanometer sized (10–20nm) CNFs inside the hybrid organic–inorganic SSQ-UA copolymer. CNFs due to their crystalline structure drastically increased Young''s moduli and the tensile strengths of the composite and decreased the thermal expansion. High thermal stability of polysilsesquioxane improved heat resistance of CNFs. [Copyright &y& Elsevier]

Abstract: Chitin nanofibrils, which are prepared from dried crab shells by a grinding method, are newly developed natural materials with uniform widths of approximately 10–20nm. The bioactivities of chitin nanofibrils have not been investigated. In this study, we examined the preventive effects of chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis. The results indicated that chitin nanofibrils improved clinical symptoms and suppressed ulcerative colitis. Furthermore, chitin nanofibrils suppressed myeloperoxidase activation in the colon and decreased serum interleukin-6 concentrations. Conversely, chitin powder did not suppress DSS-induced acute ulcerative colitis. Our results suggested that chitin nanofibrils have potential as a functional substance for inflammatory bowel disease patients. [Copyright &y& Elsevier]

Chitin nanofibers were isolated from the cell walls of five different types of mushrooms by the removal of glucans, minerals, and proteins, followed by a simple grinding treatment under acidic conditions. The Chitin nanofibers thus obtained have a uniform structure and a long fiber length. The width of the nanofibers depended on the type of mushrooms and varied in the range 20 to 28 nm. The Chitin nanofibers were characterized by elemental analyses, FT-IR spectra, and X-ray diffraction profiles. The results showed that the α-chitin crystal structure was maintained and glucans remained on the nanofiber surface. [ABSTRACT FROM AUTHOR]

Optically transparent chitin nanofiber composites were fabricated with 11 different types of (meth)acrylic resins. Chitin nanofibers significantly increased the Young's moduli and the tensile strengths, and decreased the thermal expansion of all (meth)acrylic resins due to the reinforcement effect of chitin nanofibers having an extended crystal structure. [ABSTRACT FROM AUTHOR]

Highly chemoselective N-phthaloylations of chitosan were achieved by reaction in aqueous acetic acid media in concentrations from 0 to 10.0%. The degree of substitution (DS) values of phthaloyl groups determined by elemental analysis and 1H NMR were approximately 1. The 1H and 13C NMR spectra strongly support the structural uniformity of N-phthaloyl chitosan. [ABSTRACT FROM AUTHOR]

Abstract: Highly regioselective chitosan derivatives were achieved by copper-catalyzed Huisgen cycloaddition, known as an ideal reaction for click chemistry, using 6-azido-6-deoxy-chitosan derivative. The azide moiety introduced through regioselective bromination and azidation of chitosan was successfully converted with ethynyl compounds having functional groups (hydroxymethyl and phenyl groups) in the presence of copper(II) sulfate, sodium ascorbate and triethylamine. FTIR, elemental analysis, 1H NMR, and 13C NMR spectra showed that C-6 positions of the chitosan derivative were regioselectively transferred by these functional groups with 1,4-triazole linker, and the DS values were approximately 1. [Copyright &y& Elsevier]

Abstract: Although extensive research is in progress on the use of chitin and chitosan, poor solubility has been one of the main obstacles to their effective utilization. Introduction of carbohydrate branches into chitin and chitosans gave branched polysaccharide analogs, which showed good water solubility and induced new chemical and biological functions. In this study, hyperbranched chitosan derivatives were synthesized by introducing chitosan branches to the amino group of chitosan by the reductive N-alkylation method. Compared with the linear chitosan, the hyperbranched derivatives exhibited improved water solubility in the physiological conditions (pH 6.8). Although the viscosity of starting chitosans for main chain increased with the increase in their weight average molecular weights (80–190kDa), the corresponding hyperbranched chitosan derivatives showed relatively low viscosities. [Copyright &y& Elsevier]

Abstract: Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or “sleeping sickness,” which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC50 value: 1nM) to eliminate trypanosomes in human infective strain cultures. [ABSTRACT FROM AUTHOR]

Abstract: Chitin nanofibers were prepared from dried chitin by fibrillation using a grinding apparatus. The fibrillated chitin samples were observed by FE-SEM and were found to have a fine nanofiber network; the structure was highly uniform with a width of 10–20nm and a high aspect ratio. Mechanical treatment under acidic conditions is the key to fibrillating dry chitin. The cationization of amino groups on the chitin fiber facilitates fibrillation into nanofibers by electrostatic repulsions. Even though the degree of substitution of amino groups was only 3.9%, it was enough to break the strong hydrogen bonds between the nanofibers. Furthermore, optically transparent nanocomposites using chitin nanofibers with acrylic resin were prepared to examine the fibrillation properties of dry chitin and nanofiber homogeneity. Since dried chitin was fully fibrillated, the optical losses of these composites were less than 2% even after the drying process. Moreover the films were characterized by X-ray diffraction, and TGA. [Copyright &y& Elsevier]

Abstract: The trypanosome alternative oxidase (TAO) functions in the African trypanosomes as a cytochrome-independent terminal oxidase, which is essential for their survival in the mammalian host and as it does not exist in the mammalian host is considered to be a promising drug target for the treatment of trypanosomiasis. In the present study, recombinant TAO (rTAO) overexpressed in a haem-deficient Escherichia coli strain has been solubilized from E. coli membranes and purified to homogeneity in a stable and highly active form. Analysis of bound iron detected by inductively coupled plasma-mass spectrometer (ICP-MS) reveals a stoichiometry of two bound iron atoms per monomer of rTAO. Confirmation that the rTAO was indeed a diiron protein was obtained by EPR analysis which revealed a signal, in the reduced forms of rTAO, with a g-value of 15. The kinetics of ubiquiol-1 oxidation by purified rTAO showed typical Michaelis–Menten kinetics (K m of 338μM and V max of 601μmol/min/mg), whereas ubiquinol-2 oxidation showed unusual substrate inhibition. The specific inhibitor, ascofuranone, inhibited the enzyme in a mixed-type inhibition manner with respect to ubiquinol-1. [Copyright &y& Elsevier]

[Display omitted] Here we show a novel colorimetric sensor system with a photo-induced colorimetric reaction of N , N' -bis[2-(trimethylammonium)ethyl]-1,8:4,5-naphthalenetetracarboxdiimide (TENDI) to detect and quantify carboxylate derivatives. In the presence of CH 3 COONa, TENDI aqueous solution under UV irradiation shows a photo-induced colorimetric reaction, which is due to the production of naphthalenediimide (NDI)-based radical anions whose absorbance peaks appear at around 400–600 nm. In contrast, no color changes are observed in the cases of diverse inorganic salts. In addition, TENDI shows another ability to discriminate the structural features of carboxylate derivatives by color tone. Moreover, interestingly, the Hill equation can approximate the relationship between carboxylate concentrations and absorbance values on the maximum absorbance wavelengths of the absorbance peaks due to the NDI-radical anions. [ABSTRACT FROM AUTHOR]

Surface wrinkling to fabricate hierarchical surface topographies has attracted much attention because of the potential and multifunctional applications of hierarchical surface wrinkles beyond uniform wrinkles. Although many reports have described the preparation of hierarchical wrinkles induced by mechanical stress and heat, fabrication through drying-induced shrinkage has hardly been reported. Here we introduce hierarchical surface wrinkles and bumps generated on a chitosan film via the preparation of double-skin layers with κ- and ι-carrageenans, respectively, and subsequent drying. Double-skin layers are fabricated on a swollen chitosan film, called a chitosan hydrogel film, that is soaked first in κ- or ι-carrageenan solution and then in water to remove excess adsorbed κ- or ι-carrageenan. After the film is dried, hierarchical microscopic surface architectures are observed. In the case of the κ-carrageenan system, the wrinkles are hierarchical, consisting of wrinkles (6.2 ± 2.8 μm) that have smaller buckles (0.23 ± 0.09 μm). We reveal that the wrinkles or the smaller buckles are caused by plane inhomogeneous shrinkage between the κ-carrageenan layer and the chitosan film or by the aggregation of the κ-carrageenan layer upon drying, respectively. Interestingly, the ι-carrageenan system showed hierarchical bumps consisting of semispherical bumps (5.6 ± 2.1 μm) that have smaller bumps (0.78 ± 0.27 μm). We reveal that the larger bumps are generated during the immersion of the chitosan hydrogel film into ι-carrageenan solution. The smaller bumps are generated by the aggregation of the ι-carrageenan layer that occurs during drying; this process requires the plane compression strain caused by the shrinkage of the chitosan hydrogel film. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Chitin nanofibers were prepared from prawn shell by a simple grinding treatment after the removal of proteins and minerals. Since the exoskeleton of prawn is made up of a finer structure than crab shell, nano-fibrillation of prawn shell was easier than that of crab shell, which allow chitin nanofibers to be prepared under neutral pH conditions. The prepared chitin nanofibers were highly uniform and the width was 10–20nm, which was similar to nanofibers from crab shell treated under acidic conditions. The preparation method for chitin nanofibers from prawn shells without an acidic chemical was applicable to many prawn species. [Copyright &y& Elsevier]

In order to synthesize a promising material for developing a novel peptide/protein delivery system, guanidinylation of chitooligosaccharides with 1-amidinopyrazole hydrochloride was investigated herein. The production of guanidinylated chitooligosaccharides was demonstrated by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and elemental analyses. Interestingly, we found that the reducing end in the guanidinylated chitooligosaccharides was converted to a cyclic guanidine structure (2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose structure). This reaction was carefully proven by the guanidinylation of d-glucosamine. Although this is not the first report on the synthesis of the 2-[(aminoiminomethyl)amino]-2-deoxy-d-glucose, it has provided a rational synthetic route using the high reactivity of the reducing end. Furthermore, we found that the interaction between chitooligosaccharides and bovine serum albumin is weak when in a neutral pH environment; however, it is significantly improved by guanidinylation. The guanidinylated chitooligosaccharides are useful not only for the development of a novel drug delivery system but also as a chitinase/chitosanase inhibitor and an antibacterial agent. [ABSTRACT FROM AUTHOR]

Malaria is one of the three major global health threats. Drug development for malaria, especially for its most dangerous form caused by Plasmodium falciparum, remains an urgent task due to the emerging drug-resistant parasites. Exploration of novel antimalarial drug targets identified a trifunctional enzyme, malate quinone oxidoreductase (MQO), located in the mitochondrial inner membrane of P. falciparum (PfMQO). PfMQO is involved in the pathways of mitochondrial electron transport chain, tricarboxylic acid cycle, and fumarate cycle. Recent studies have shown that MQO is essential for P. falciparum survival in asexual stage and for the development of experiment cerebral malaria in the murine parasite P. berghei, providing genetic validation of MQO as a drug target. However, chemical validation of MQO, as a target, remains unexplored. In this study, we used active recombinant protein rPfMQO overexpressed in bacterial membrane fractions to screen a total of 400 compounds from the Pathogen Box, released by Medicines for Malaria Venture. The screening identified seven hit compounds targeting rPfMQO with an IC50 of under 5 μM. We tested the activity of hit compounds against the growth of 3D7 wildtype strain of P. falciparum, among which four compounds showed an IC50 from low to sub-micromolar concentrations, suggesting that PfMQO is indeed a potential antimalarial drug target. [ABSTRACT FROM AUTHOR]

The emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni), make the development of new antischistosomal drugs urgent. The parasite's mitochondrion is an attractive target for drug development, because this organelle is essential for survival throughout the parasite's life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercaria motility that have been reported to affect mitochondrion-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against the motility of schistosomula ( in vitro ) and adults ( ex vivo ). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% of that obtained in the vehicle control. Notably, ascofuranone showed the highest activity, with a 98% reduction of the worm burden, suggesting the potential for the development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and nonmitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are a feasible target for drug development.

The development of anion sensors for selective detection of a specific anion is a crucial research topic. We previously reported a selective photo-induced colorimetric reaction of 1-methyl-3-( N -(1,8-naphthalimidyl)ethyl)imidazolium (MNEI) having a cationic receptor in the presence of molecules having multiple carboxy groups, such as succinate, citrate, and polyacrylate. However, the mechanism underlying this reaction was not clarified. Here, we investigate the photo-induced colorimetric reaction of N -[2-(trimethylammonium)ethyl]-1,8-naphthalimide (TENI), which has a different cationic receptor from MNEI and undergoes the photo-induced colorimetric reaction, and its analogues to clarify the reaction mechanism. The TENI analogues having substituents on the naphthalene ring provide important evidence, suggesting that the colorimetric chemical species were radical anions generated via photo-induced electron transfer from carboxylate to the naphthalimide derivative. The generation of the naphthalimide-based radical anion is verified by 1 H NMR and cyclic voltammetry analyses, and photo-reduction of methylene blue is mediated by TENI. In addition, the role of the cationic receptor for the photo-induced colorimetric reaction is investigated with TENI analogues having different hydrophilic groups instead of the trimethylammonium group. Interestingly, the photo-induced colorimetric reaction is observed in a nonionic analogue having a polyethylene glycol group, indicating that the colorimetric reaction does not require a cationic receptor. On the other hand, we reveal that the trimethylammonium group stabilizes the radical anion species. These generation and stabilization phenomena of naphthalimide-based radical anion species will contribute to the development of sophisticated detection systems specific for carboxylate., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Chitins obtained by fermentation of shrimp wastes using Lactobacillus brevis with and without further inoculations with Rhizopus oligosporus resulted in higher molecular weight than the commercial biopolymer. After grinding in acidic conditions, the attained chitins were fully fibrillated by a mechanical treatment throughout ten passes in a high-pressure water jet system as evidenced by field-emission scanning electron microscopy. The chitin sample crystallinities decreased from 85% to 68%. A previous chitin sample bleaching, as well as the sonication of chitin nanofiber suspensions, enhanced the transparency in the resulting nanofiber sheets. Suspensions and sheets of chitin extracted by L. brevis with successive R. oligosporus inoculations displayed higher transmittance and acetylation degree, as well as improved mechanical properties compared to chitin extracted with only L. brevis. Mechanical studies demonstrated that Young's modulus of the nanofibers using this biological chitin was remarkably higher than that for the commercial product, an important characteristic in polymer reinforcements., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de novo biosynthesis pathway. It is located on the mitochondrial inner membrane and contributes to the respiratory chain by shuttling electrons to the ubiquinone pool. We have discovered ascofuranone ( 1 ), a natural compound produced by Acremonium sclerotigenum , and its derivatives are a potent class of HsDHODH inhibitors. We conducted a structure-activity relationship study and have identified functional groups of 1 that are essential for the inhibition of HsDHODH enzymatic activity. Furthermore, the binding mode of 1 and its derivatives to HsDHODH was demonstrated by co-crystallographic analysis and we show that these inhibitors bind at the ubiquinone binding site. In addition, the cytotoxicities of 1 and its potent derivatives 7 , 8 , and 9 were studied using human cultured cancer cells. Interestingly, they showed selective and strong cytotoxicity to cancer cells cultured under microenvironment (hypoxia and nutrient-deprived) conditions. The selectivity ratio of 8 under this microenvironment show the most potent inhibition which was over 1000-fold higher compared to that under normal culture condition. Our studies suggest that under microenvironment conditions, cancer cells heavily depend on the pyrimidine de novo biosynthesis pathway. We also provide the first evidence that 1 and its derivatives are potential lead candidates for drug development which target the HsDHODH of cancer cells living under a tumor microenvironment.

This study investigated the prophylactic effects of orally administered surface-deacetylated chitin nanofibers (SDACNFs) and chitosan against 5-fluorouracil (5-FU)-induced intestinal mucositis, which is a common side effect of 5-FU chemotherapy. SDACNFs and chitosan abolished histological abnormalities associated with intestinal mucositis and suppressed hypoproliferation and apoptosis of intestinal crypt cells. These results indicate that SDACNF and chitosan are useful agents for preventing mucositis induced by anti-cancer drugs.

We previously developed biobased wrinkled surfaces based on wood mimetic skins in which microscopic wrinkles were fabricated on a chitosan film by immersion in a phenolic acid solution, horseradish peroxidase-catalyzed surface reaction, and drying. Here, we prepared a diverse range of wrinkled films by immersion treatment at 30, 40, 50, and 60 °C in p-coumaric acid and then investigated the correlation between wrinkle morphology and mechanical properties. Wrinkle wavelengths gradually decreased as the immersion temperature increased as well as the previous report. In order to clarify the mechanisms responsible for the different wrinkle morphologies, the films were subjected to elastic moduli measurement and GPC analysis after immersion treatment. These experiments provided evidence that the chitosan around the film surface decomposed along with the immersion process. The decomposition was accelerated by higher immersion temperature, suggesting that higher temperatures led to the formation of softer skins, inducing smaller wrinkles. In fact, wrinkle morphologies with this system were predominately determined by the hardness of the wood mimetic skins. This phenomenon is consistent with the fundamentals of surface wrinkling in nature. This study is the first to demonstrate that artificial wrinkling triggered by water evaporation can be controlled by precise control of the surface hardness of soft material.

Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm²), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation.

Human mesenchymal stem cells (MSCs) are expected to have utility as a cell source in regenerative medicine. Because we previously reported that suppression of the Wnt/β-catenin signal enhances hepatic differentiation of human MSCs, we synthesized twenty-three derivatives of small molecule compounds originally reported to suppress the Wnt/β-catenin signal in human colorectal cancer cells. We then screened these compounds for their ability to induce hepatic differentiation of human UE7T-13 MSCs. After screening using WST assay, TCF reporter assay, and albumin mRNA expression, IC-2, a derivative of ICG-001, was identified as a potent inducer of hepatic differentiation of human MSCs. IC-2 potently induced the expression of albumin, complement C3, tryptophan 2,3-dioxygenase (TDO2), EpCAM, C/EBPα, glycogen storage, and urea production. Furthermore, we examined the effects of IC-2 on human bone marrow mononuclear cell fractions sorted according to CD90 and CD271 expression. Consequently, CD90 + CD271 + cells were found to induce the highest production of urea and glycogen, important hepatocyte functions, in response to IC-2 treatment. CD90 + CD271 + cells also highly expressed albumin mRNA. As the CD90 + CD271 + population has been reported to contain a rich fraction of MSCs, IC-2 apparently represents a potent inducer of hepatic differentiation of human MSCs.

Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young's modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young's modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials.

A new and simple approach for surface wrinkling inspired by polymer assemblies in wood fibers is introduced. A hard skin is synthesized on a linear polysaccharide support that resembles the structural units of the cell wall. This skin, a wood mimetic layer, is produced through immersion in a solution containing phenolic precursor and subsequent surface reaction by horseradish peroxidase. A patterned surface with micron-scale wrinkles is formed upon drying and as a result of inhomogeneous shrinkage. We demonstrate that the design of the wrinkled surfaces can be controlled by the molecular structure of the phenolic precursor, temperature, and drying stress. It is noteworthy that this is a totally bio-based system involving green materials and processes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota.

This study evaluated the effects of oral administration of surface-deacetylated chitin nanofibers (SDACNFs) on hypercholesterolemia using an experimental model. All rats were fed a high cholesterol diet with 1% w/w cholesterol and 0.5% w/w cholic acid for 28 days. Rats were divided equally into four groups: the control group was administered 0.05% acetic acid dissolved in tap water, and the SDACNF, chitosan (CS), and cellulose nanofiber (CLNF) groups were administered 0.1% CNF, CS, or CLNF dissolved in the tap water, respectively, during the experimental period. Changes in body weight, intake of food and water, and organ weight were measured. Serum blood chemistry and histopathological examination of the liver were performed. Administration of SDACNF did not affect body weight change, food and water intake, or organ weights. Administration of SDACNF and CS decreased the diet-induced increase in serum total cholesterol, chylomicron, very-low-density lipoprotein, and phospholipid levels on day 14. Moreover, oral administration of SDACNFs suppressed the increase of alanine transaminase levels on day 29 and suppressed vacuolar degeneration and accumulation of lipid droplets in liver tissue. These data indicate that SDACNF has potential as a functional food for patients with hypercholesterolemia.

Previous reports indicate that the beneficial effect of chitin nanofibrils (CNFs), and chitosan nanofibrils (CSNFs) for wound healing. In this study, the wound healing effects of superficially deacetylated chitin nanofibrils (SDACNFs) were evaluated using an experimental model. In the experiments using circular excision wound model, SDACNFs induced re-epithelium and proliferation of the fibroblasts and collagen tissue. In the chitin, CNFs, and CSNFs, on the other hand, the e-epithelium and proliferation of the fibroblasts and collagen tissue were not induced perfectly compared with the SDACNFs group. In particular, re-epithelization was observed on day 4 in the only SDACNF group. Moreover, SDACNFs did not induce severe systemic inflammation in the linear incision wound model. The data indicated that SDACNFs effectively induced the proliferation and re-modeling phases compared with chitin, CNFs, and CSNFs in the wound. These data indicate that SDACNFs can be beneficial as a new biomaterial for wound healing., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Chitin (β-(1-4)-poly-N-acetyl-D-glucosamine) is widely distributed in nature and is the second most abundant polysaccharide after cellulose. It is often converted to its more deacetylated derivative, chitosan. Previously, many reports have indicated the accelerating effects of chitin, chitosan, and its derivatives on wound healing. More recently, chemically modified or nano-fibrous chitin and chitosan have been developed, and their effects on wound healing have been evaluated. In this review, the studies on the wound-healing effects of chitin, chitosan, and its derivatives are summarized. Moreover, the development of adhesive-based chitin and chitosan are also described. The evidence indicates that chitin, chitosan, and its derivatives are beneficial for the wound healing process. More recently, it is also indicate that some nano-based materials from chitin and chitosan are beneficial than chitin and chitosan for wound healing. Clinical applications of nano-based chitin and chitosan are also expected.

Trypanosoma brucei is a parasite that causes human African trypanosomiasis (HAT). The parasites depend on the cyanide-insensitive trypanosome alternative oxidase (TAO) for their vital aerobic respiration. Ascofuranone (AF), a potent and specific sub-nanomolar inhibitor of the TAO quinol oxidase, is a potential novel drug with selectivity for HAT, because mammalian hosts lack the enzyme. To elucidate not only the inhibition mechanism but also the inhibitor-enzyme interaction, AF derivatives were designed and synthesized, and the structure-activity relationship was evaluated. Here we identified the pharmacophore of AF that interacts with TAO. The detailed inhibitory profiles indicated that the 1-formyl and 6-hydroxyl groups, which might contribute to intramolecular hydrogen bonding and/or serve as hydrogen-bonding donors, were responsible for direct interaction with the enzyme.

Synthesis of a highly regioselective amphiprotic chitosan derivative was achieved by click chemistry. The Huisgen cycloaddition between 6-azido-6-deoxy-N-pthaloyl-chitosan and methyl propiolate was successfully carried out in the presence of Cu(I) catalyst. After the reaction, both the phthaloyl protecting group and methyl group were completely removed by hydrazine. FT-IR and NMR spectroscopy as well as elemental analysis strongly support the structural uniformity of the desired amphiprotic chitosan derivative, which has both a carboxylic group with a 1,4-triazole linker at the C-6 position and an amino group at the C-2 position per repeating unit. The amphiprotic chitosan derivative was soluble under both acidic and basic aqueous conditions. In contrast, it formed nanoparticle under neutral condition due to the interaction between the positive (-NH(3)(+)) and negative (-COO(-)) ions on the chitosan derivative., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We investigated the effect of fucoidan, a sulfated polysaccharide, on acceleration of healing of experimental cartilage injury in a rabbit model. An injured cartilage model was surgically created by introduction of three holes, one in the articular cartilage of the medial trochlea and two in the trochlear sulcus of the distal femur. Rabbits in three experimental groups (F groups) were orally administered fucoidan of seven different molecular weights (8, 50, 146, 239, 330, 400, or 1000 kD) for 3 weeks by screening. Control (C group) rabbits were provided water ad libitum. After the experimental period, macroscopic examination showed that the degree of filling in the fucoidan group was higher than that in the C group. Histologically, the holes were filled by collagen fiber and fibroblasts in the C group, and by chondroblasts and fibroblasts in the F groups. Image analysis of Alcian blue- and safranin O-stained F-group specimens showed increased production of glycosaminoglycans (GAGs) and proteoglycans (PGs), respectively. Some injured holes were well repaired both macroscopically and microscopically and were filled with cartilage tissues; cartilage matrices such as PGs and GAGs were produced in groups F 50, F 146, and F 239. Thus, fucoidan administration enhanced morphologically healing of cartilage injury.

We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5-40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110-138 kDa) and high-molecular-weight fucoidan (HMWF: 300-330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

Chitin nanofibers are prepared from the exoskeletons of crabs and prawns by a simple mechanical treatment after the removal of proteins and minerals. The obtained nanofibers have fine nanofiber networks with a uniform width of approximately 10-20 nm and a high aspect ratio. The method used for chitin-nanofiber isolation is also successfully applied to the cell walls of mushrooms. They form a complex with glucans on the fiber surface. A grinder, a Star Burst atomization system, and a high speed blender are all used in the mechanical treatment to convert chitin to nanofibers. Mechanical treatment under acidic conditions is the key to facilitate fibrillation. At pH 3-4, the cationization of amino groups on the fiber surface assists nano-fibrillation by electrostatic repulsive force. By applying this finding, we also prepared chitin nanofibers from dry chitin powder. Chitin nanofibers are acetylated to modify their surfaces. The acetyl DS can be controlled from 1 to 3 by changing the reaction time. An acetyl group is introduced heterogeneously from the surface to the core. Nanofiber morphology is maintained even in the case of high acetyl DS. Optically transparent chitin nanofiber composites are prepared with 11 different types of acrylic resins. Due to the nano-sized structure, all of the composites are highly transparent. Chitin nanofibers significantly increase the Young's moduli and the tensile strengths and decrease the thermal expansion of all acrylic resins due to the reinforcement effect of chitin nanofibers. Chitin nanofibers show chiral separation ability. The chitin nanofiber membrane transports the d-isomer of glutamic acid, phenylalanine, and lysine from the corresponding racemic amino acid mixtures faster than the corresponding l-isomer. The chitin nanofibers improve clinical symptoms and suppress ulcerative colitis in a DSS-induced mouse model of acute ulcerative colitis. Moreover, chitin nanofibers suppress myeloperoxidase activation in the colon and decrease serum interleukin-6 concentrations.

Chitin nanofibers were acetylated to modify the fiber surface and were characterized in detail. The acetyl DS could be controlled from 0.99 to 2.96 by changing the reaction time. FT-IR spectra indicate that chitin nanofibers were acetylated completely after 50 min reaction time. X-ray diffraction profiles and TGA curves show that the chitin nanofibers were acetylated heterogeneously from the surface to the core. SEM images show that fiber shape was maintained even in the high-DS sample and that the thickness of the nanofibers increased with the introduction of bulky acetyl groups. Acetylated chitin nanofiber composites were fabricated with acrylic resin with the fiber content of approximately 25 wt %. Due to the size effect, all nanocomposites had high transparency, despite the variety of acetyl DS, and the transparency of the chitin nanofiber composite was less sensitive to acetylation. By only 1 min acetylation, the moisture absorption of the nanocomposite drastically decreased from 4.0 to 2.2%. Although the coefficient of thermal expansion (CTE) of the tricyclodecane dimethanol dimethacrylate (TCDDMA) resin was 6.4 x 10(-5) degrees C(-1), the CTE of the chitin nanofiber/TCDDMA composite decreased to 2.3 x 10(-5) degrees C(-1) by the reinforcement effect of the chitin nanofibers with low thermal expansion.