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1.
Planta ; 257(2): 39, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650257

RESUMO

MAIN CONCLUSION: The xyloglucans of all aquatic Araceae species examined had unusual structures compared with those of other non-commelinid monocotyledon families previously examined. The aquatic Araceae species Lemna minor was earlier shown to have xyloglucans with a different structure from the fucogalactoxyloglucans of other non-commelinid monocotyledons. We investigated 26 Araceae species (including L. minor), from five of the seven subfamilies. All seven aquatic species examined had xyloglucans that were unusual in having one or two of three features: < 77% XXXG core motif [L. minor (Lemnoideae) and Orontium aquaticum (Orontioideae)]; no fucosylation [L. minor (Lemnoideae), Cryptocoryne aponogetonifolia, and Lagenandra ovata (Aroideae, Rheophytes clade)]; and > 14% oligosaccharide units with S or D side chains [Spirodela polyrhiza and Landoltia punctata (Lemnoideae) and Pistia stratiotes (Aroideae, Dracunculus clade)]. Orontioideae and Lemnoideae are the two most basal subfamilies, with all species being aquatic, and Aroideae is the most derived. Two terrestrial species [Dieffenbachia seguine and Spathicarpa hastifolia (Aroideae, Zantedeschia clade)] also had xyloglucans without fucose indicating this feature was not unique to aquatic species.


Assuntos
Araceae , Glucanos , Xilanos , Oligossacarídeos
2.
Curr Biol ; 33(2): R65-R67, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36693310

RESUMO

A newly discovered pathway relying on the production and modification of periplasmic oligosaccharides is required for proper cell-envelope homeostasis and antibiotic resistance in Gram-negative bacteria.


Assuntos
Parede Celular , Glucanos , Glucanos/metabolismo , Membrana Celular/metabolismo , Parede Celular/metabolismo , Bactérias Gram-Negativas , Fenômenos Fisiológicos Bacterianos , Proteínas de Bactérias/metabolismo
3.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688789

RESUMO

This study was conducted with a perception that fructose-rich niches may inhabit novel species of lactic acid bacteria that are gaining importance as probiotics and for the production of exopolysaccharides that have applications in food and pharmaceuticals. Recently, some Lactobacillus species have been reclassified as fructophilic lactic acid bacteria due to their preference for fructose over glucose as a carbon source. These bacteria are likely to be found in fructose rich niches such as flower nectar and insects that feed on it. We explored the butterfly gut and acquired a new isolate, designated as F1, of fructophilic lactic acid bacteria, which produces a glucan-type exopolysaccharide. Whole genome sequencing and in silico analysis revealed that F1 has significantly lower average nucleotide identity and DNA-DNA hybridization values as compared to its closest Apilactobacillus neighbors in phylogenetic analysis. Therefore, we declare the isolate F1 as a novel Apilactobacillus species with the proposed name of Apilactobacillus iqraium F1. Genome mining further revealed that F1 harbors genes for exopolysaccharide synthesis and health-promoting attributes. To this end, F1 is the only Apilactobacillus species harboring three diverse α-glucan-synthesis genes that cluster with different types of dextransucrases in the dendrogram. Moreover, many nutritional marker genes, as well as genes for epithelial cell adhesion and antimicrobial synthesis, were also detected suggesting the probiotic attributes of F1. Overall analysis suggests A. iqraium sp. F1 be a potential candidate for various health beneficial and pharmaceutical applications.


Assuntos
Borboletas , Lactobacillales , Probióticos , Animais , Borboletas/genética , Borboletas/metabolismo , Filogenia , Lactobacillales/genética , Frutose/metabolismo , Probióticos/metabolismo , Glucanos/metabolismo , DNA
4.
Int J Biol Macromol ; 228: 692-705, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36566807

RESUMO

The cancer immunotherapeutic effect of a carboxymethylated ß-d-glucan (CMPTR)/iron oxide nanoparticles (IONPs) system (CMPTR/IONPs) were investigated by using cell culture of bone marrow-derived macrophages (BMDMs) and B16F10 melanoma skin cancer-bearing mouse model. When compared with that of control group, CMPTR/IONPs-treated M2-like BMDMs exhibited upregulated M1 biomarkers expression, significantly inhibited the migration of B16F10 cancer cells (p < 0.05), and had the highest apoptotic percentage of B16F10 cancer cells (80.39 ± 8.73 %) in co-culture system. Intratumoral administration of CMPTR/IONPs significantly (p < 0.05) suppressed tumor growth (46.58 % based on tumor weight) in mice and enhanced the M1/M2 ratio from 0.40 ± 0.09 (control group) to 6.64 ± 1.61 in tumor associated macrophages (TAMs) which was higher than that of in CMPTR (1.27 ± 0.38), IONPs (1.38 ± 0.17). CMPTR/IONPs treatment also promoted apoptosis in cancer cells and increased the infiltration of CD4 and CD8 T-lymphocytes in tumor tissues. These results could be due to the combined effects of CMPTR and IONPs in the CMPTR/IONPs system, possibly mediated by the activation of NF-κB and IRF5 pathways for inducing M1 macrophages polarization and had potential cancer immunotherapeutic applications.


Assuntos
Melanoma , Nanopartículas , Animais , Camundongos , Macrófagos Associados a Tumor/patologia , Glucanos/uso terapêutico , Melanoma/tratamento farmacológico , Imunoterapia , Nanopartículas Magnéticas de Óxido de Ferro , Fatores Reguladores de Interferon
5.
Plant Cell Environ ; 46(2): 391-404, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36478232

RESUMO

Cell walls are essential for plant growth and development, providing support and protection from external environments. Callose is a glucan that accumulates in specialized cell wall microdomains including around intercellular pores called plasmodesmata. Despite representing a small percentage of the cell wall (~0.3% in the model plant Arabidopsis thaliana), callose accumulation regulates important biological processes such as phloem and pollen development, cell division, organ formation, responses to pathogenic invasion and to changes in nutrients and toxic metals in the soil. Callose accumulation modifies cell wall properties and restricts plasmodesmata aperture, affecting the transport of signaling proteins and RNA molecules that regulate plant developmental and environmental responses. Although the importance of callose, at and outside plasmodesmata cell walls, is widely recognized, the underlying mechanisms controlling changes in its synthesis and degradation are still unresolved. In this review, we explore the most recent literature addressing callose metabolism with a focus on the molecular factors affecting callose accumulation in response to mutualistic symbionts and pathogenic elicitors. We discuss commonalities in the signaling pathways, identify research gaps and highlight opportunities to target callose in the improvement of plant responses to beneficial versus pathogenic microbes.


Assuntos
Arabidopsis , Plasmodesmos , Plantas/metabolismo , Arabidopsis/genética , Glucanos/metabolismo , Parede Celular/metabolismo
6.
Biomacromolecules ; 24(1): 358-366, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36525635

RESUMO

Hydrogels were prepared at high solid contents (70-100 g/L) with cellulose nanocrystals (CNC) and very short xyloglucans (XGs). At 70 g/L, CNCs form cholesteric liquid crystals regularly spaced by a distance of 30 nm. This structure was preserved after adsorption of XG with a molar mass (Mw) of 20,000 g/mol (XG20) but was lost at 40,000 g/mol (XG40). Rheological measurements discriminated domains where an increasing Mw from XG20 to XG40 gave rise to drastic changes in storage moduli (on 3 orders of magnitude). At 40,000 g/mol, transient systems were obtained and a re-entrant glass-gel-glass transition was observed with increasing XG concentrations. This was interpreted in terms of the length and stiffness of the chain in relation to the inter-CNC distance. Liquid-to-glass-to-gel transitions were attributed to an XG adsorption type according to train or trail conformations or interconnected structures. Such tunable properties may further have implications on the in vivo role of XG during cell wall extension.


Assuntos
Celulose , Nanopartículas , Celulose/química , Suspensões , Glucanos/química , Nanopartículas/química
7.
Carbohydr Res ; 523: 108732, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36571946

RESUMO

Curdlan, a linear ß-1,3-glucan, was reacted with glutaric anhydride and heptanoyl chloride to afford thermoplastic curdlan esters (CrdE(HepGlu)) with a carboxylic acid side chain. CrdE(HepGlu) with a degree of substitution of the glutaric acid monoester moiety (DSGlu) in the range of 0-0.58 and that of the heptanoate moiety (DSHep = 3 - DSGlu) was prepared. The esterification of the hydroxy groups in the glucan skeleton effectively caused the cleavage of the interchain hydrogen bonds of curdlan and enhanced the formability of CrdE(HepGlu). Moreover, the flexible carboxylic acid side chain moderately affected hydrogen bonding. Thus, the glass transition temperature of CrdE(HepGlu), estimated by differential scanning calorimetry, increased with increasing DSGlu. CrdE(HepGlu) with DSGlu between 0 and 0.58 displayed high solubility in organic solvents and thermoplasticity, enabling the formation of homogeneous and free-standing films by solution casting. The mechanical properties of CrdE(HepGlu) films were evaluated by a stress-strain test, which showed that Young's modulus and the maximum stress increased with increasing DSGlu. CrdE(HepGlu) exhibited higher mechanical strength than non-hydrogen-bonded curdlan triheptanoate and hydrogen-bonded curdlan alkylcarbamates, with thermal stability comparable to that of thermally stable curdlan esters. In addition, these properties can be regulated by controlling DSGlu.


Assuntos
Ésteres , beta-Glucanas , Ésteres/química , Ácidos Carboxílicos , beta-Glucanas/química , Glucanos/química
8.
Food Res Int ; 162(Pt B): 112119, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461352

RESUMO

The 1,4-α-glucan branching enzymes (GBEs, EC 2.4.1.18) catalyze the formation of new α-1,6 branching points in starch, playing an irreplaceable role in controlling the frequency and position of branch points in glucan chains, which present several potential applications in starch industry. Previously, a thermostable GBE that originates from Rhodothermus obamensis STB05 (RoGBE) is reported to be an excellent glycosyltransferase to modify the structures of starch. However, until now, how to control the length of the transferred glucan chains is still a challenge. Structural analysis of RoGBE shows that the residue at amino acid site 489 connects with the reducing end of the substrate, which may determine the chain length of binding oligosaccharides. The substitutions of Gln at this site with Arg, Glu and Gly result in alternations at catalytic activities and transglycosylation patterns of GBE. Specifically, the Q489E, and Q489R mutants had 5-10 % increases in catalytic activities, the Q489G shows that a slight decrease in activity. versus modified maltodextrin with wild-type RoGBE, maltodextrin incubated with Q489G, Q489E, and Q489R mutants show a 4.17 %-22.43 % increase in the ratio of glucan chains with DP < 13 in the oligosaccharide chains of modified maltodextrin. Crystallographic analyses and simulations were performed to reveal the structural alternations mediated by the introduced mutations. These results are important in the context of understanding the mechanism of action of the thermostable glycosyltransferase and can help develop more functional glycosyltransferases for controlling the glucan chains of polysaccharides.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana , Glucanos , Enzima Ramificadora de 1,4-alfa-Glucana/genética , Domínio Catalítico , Polissacarídeos , Amido , Glicosiltransferases/genética
9.
Int J Mol Sci ; 23(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36555628

RESUMO

Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS-BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut.


Assuntos
Insuficiência Renal Crônica , beta-Glucanas , Camundongos , Animais , Lipopolissacarídeos , Candida/metabolismo , Glucanos , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Toxinas Urêmicas , Interleucina-6 , Insuficiência Renal Crônica/metabolismo , Fibrose , beta-Glucanas/metabolismo , Inflamação , Modelos Animais de Doenças
10.
Mar Drugs ; 20(12)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36547919

RESUMO

Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or ß-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.


Assuntos
Glucanos , Feófitas , Humanos , Glucanos/farmacologia , Polissacarídeos/farmacologia , Preparações Farmacêuticas
11.
J Nanobiotechnology ; 20(1): 477, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369044

RESUMO

BACKGROUND: Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. RESULTS: Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ+ effector memory T-helper/memory cells, IL-17A+ total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A+ total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A+ T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ+ late effector CTLs and effector memory T-helper/memory cells, IL-17A+ total CTLs, late effector CTLs, and CXCL10+ myeloid cells in blood, as well as lung CXCL10+ plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs. CONCLUSIONS: Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Nanopartículas , Infecções por Orthomyxoviridae , Suínos , Animais , Interleucina-17 , Glucanos , Administração Intranasal , Infecções por Orthomyxoviridae/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Anticorpos Antivirais
12.
Drug Deliv ; 29(1): 3328-3339, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36369833

RESUMO

Drug distribution relies heavily on polymers, which also offer a variety of benefits like controlled release, targeted release, prolonged release, etc. Due to their low toxicity and great safety, biodegradable polymers are highly preferred. The exopolysaccharide known as pullulan is generated from a fungus known as Aureobasidium pullulan. It has many different qualities, including biodegradability, appropriate adhesion, antioxidant, film-forming capacity, blood compatibility, mucosal adhesion, etc. However, its application in the pharmaceutical industry is restricted by its insolubility in organic solvents, mechanical characteristics, and lack of macromolecule-carrying ability groups. This review provides an overview of the modifications made to pullulan, including periodate oxidation, etherification, esterification, sulfation, urethane derivatization, PEG incorporation, and cationization, to enhance its solubility in organic solvents, mechanical properties, pH sensitivity, drug delivery, anticoagulant, and antimicrobial properties. Pullulan has nine active hydroxyl groups in its structure that react chemically that can be used for physicochemical modification to produce pullulan derivatives. A key area of pullulan research has been pullulan modification, which has demonstrated enhanced solubility, pH-sensitive targeting, broadened horizons for delivery systems, anticoagulation, and antibacterial properties.


Assuntos
Sistemas de Liberação de Medicamentos , Glucanos , Glucanos/química , Preparações Farmacêuticas/química , Polímeros , Solventes
13.
Int J Nanomedicine ; 17: 5099-5116, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36340185

RESUMO

Purpose: This study aimed to design a prototypic drug delivery system (DDS) made of an amphiphilic, pullulan (Pull)-derived biodegradable polymer for targeting the asialoglycoprotein receptor (ASGPR) overexpressed in HCC. Stearic acid (SA) was conjugated to increase the hydrophobicity of pullulan (Pull-SA). Methods: Pullulan (Pull) was linked to stearic acid (SA) after functional group modifications via EDC/NHS chemistry and characterized. Sorafenib tosylate (SRFT) was entrapped in pullulan-stearic acid nanoparticles (Pull-SA-SRFT) and its particle size, zeta potential, entrapment efficiency (EE), loading capacity (LC), and release efficiency was measured. The competence of Pull-SA-SRFT over SRFT in vitro was assessed using the ASGPR over-expressing PLC/PRF/5 hepatocellular carcinoma (HCC) cell line. This was done by studying cytotoxicity by MTT assay and chromosome condensation assay, early apoptosis by annexin-Pi staining, and late apoptosis by live-dead assay. The cellular uptake study was performed by incorporating coumarin-6 (C6) fluorophore in place of SRFT in Pull-SA conjugates. A biodistribution study was conducted in Swiss-albino mice to assess the biocompatibility and targeting properties of SRFT and Pull-SA-SRFT to the liver and other organs at 1, 6, 24, and 48 h. Results: The characterization studies of the copolymer confirmed the successful conjugation of Pull-SA. The self-assembled amphiphilic nanocarrier could proficiently entrap the hydrophobic drug SRFT to obtain an entrapment efficiency of 95.6% (Pull-SA-SRFT). Characterization of the synthesized nanoparticles exhibited highly desirable nanoparticle characteristics. In vitro, apoptotic studies urged that Pull-SA-SRFT nanoparticle was delivered more efficiently to HCC than SRFT. The cellular uptake study performed, gave propitious results in 4 hrs. The biodistribution study conducted in immunocompetent mice suggested that Pull-SA-SRFT was delivered more than SRFT to the liver when compared to other organs, and that the system was biocompatible. Conclusion: Pull-SA-SRFT is a promisingly safe, biodegradable, cell-specific nanocarrier and a potential candidate to target hydrophobic drugs to HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Sorafenibe/uso terapêutico , Distribuição Tecidual , Neoplasias Hepáticas/patologia , Glucanos/química , Receptor de Asialoglicoproteína/metabolismo , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
14.
J Appl Oral Sci ; 30: e20220158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36350873

RESUMO

OBJECTIVE: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family. Although its expression has been found in chronic oral inflammatory epithelium, this study aimed to know whether CEACAM1 in oral keratinocytes participates in host immune response against Candida albicans . METHODOLOGY: We investigated CEACAM1 expression in oral keratinocytes induced by C. albicans as well as by Candida cell wall component ß-glucan particles (ß-GPs). Furthermore, the effects of CEACAM1 on ß-GPs-induced heme oxygenase-1 (HO-1) expression and its related signals were examined. RESULTS: Fluorescence staining showed CEACAM1 expression in oral keratinocytes (RT7) cells, whereas quantitative reverse transcription (RT)-PCR indicated that both live and heat-killed C. albicans increased CEACAM1 mRNA expression in RT7 cells. Examinations using quantitative RT-PCR and western blotting indicated that CEACAM1 expression was also increased by ß-GPs derived from C. albicans . Specific siRNA for CEACAM1 decreased HO-1 expression induced by ß-GPs from C. albicans as well as the budding yeast microorganism Saccharomyces cerevisiae . Moreover, knockdown of CEACAM1 decreased ß-GPs-induced ROS activity in the early phase and translocation of Nrf2 into the nucleus. CONCLUSION: CEACAM1 in oral keratinocytes may have a critical role in regulation of HO-1 for host immune defense during Candida infection.


Assuntos
Heme Oxigenase-1 , beta-Glucanas , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/farmacologia , beta-Glucanas/farmacologia , beta-Glucanas/metabolismo , Antígeno Carcinoembrionário/metabolismo , Antígeno Carcinoembrionário/farmacologia , Molécula 1 de Adesão Celular/metabolismo , Glucanos/metabolismo , Glucanos/farmacologia , Candida , Queratinócitos , Candida albicans/fisiologia
15.
Sci Adv ; 8(45): eadd1596, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367939

RESUMO

Mixed-linkage (1,3;1,4)-ß-glucans, which are widely distributed in cell walls of the grasses, are linear glucose polymers containing predominantly (1,4)-ß-linked glucosyl units interspersed with single (1,3)-ß-linked glucosyl units. Their distribution in cereal grains and unique structures are important determinants of dietary fibers that are beneficial to human health. We demonstrate that the barley cellulose synthase-like CslF6 enzyme is sufficient to synthesize a high-molecular weight (1,3;1,4)-ß-glucan in vitro. Biochemical and cryo-electron microscopy analyses suggest that CslF6 functions as a monomer. A conserved "switch motif" at the entrance of the enzyme's transmembrane channel is critical to generate (1,3)-linkages. There, a single-point mutation markedly reduces (1,3)-linkage formation, resulting in the synthesis of cellulosic polysaccharides. Our results suggest that CslF6 monitors the orientation of the nascent polysaccharide's second or third glucosyl unit. Register-dependent interactions with these glucosyl residues reposition the polymer's terminal glucosyl unit to form either a (1,3)- or (1,4)-ß-linkage.


Assuntos
Hordeum , beta-Glucanas , Humanos , Hordeum/genética , Microscopia Crioeletrônica , Glucanos
16.
Clin Nephrol ; 98(6): 274-279, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36331016

RESUMO

INTRODUCTION: Fluid overload is an unavoidable problem in patients on peritoneal dialysis (PD) and is associated with poor outcomes. The aim of our study was to estimate ultrafiltration (UF) under different dextrose concentrations (DCs) and four peritoneal transport levels. MATERIALS AND METHODS: 70 patients, with a total of 1,848 daily treatment records and 8,266 single dwells on automated PD (APD) through Homechoice Claria with Sharesource were followed in October 2020 and categorized into two groups according to the DC (D1.5% and D2.5% groups). Baseline characteristics, peritoneal membrane characteristics, and daily PD treatment records from Sharesource were obtained. We compared UF under the different conditions. RESULTS: The mean night UF per cycle, the mean night UF corrected by fill volume (FV) per cycle, and the mean night UF corrected by FV and dwelling time (DT) per cycle were all significantly higher in the D2.5% group than in the D1.5% group (95.8 vs. 220.3 mL, 5.5 vs. 12.0%, and 5.0 vs. 11.6 0/000/minutes, all p < 0.001). However, there was no significant difference among the four transport categories in any group. CONCLUSION: This retrospective study presents precise UF measurements with two solutions at different DCs and four peritoneal transport levels. With a 2-L indwell (DT ranging from ~ 1 to 3 hours), the mean net UF rate was 1.0 mL/min in the D1.5% group and 2.3 mL/min in the D2.5% group.


Assuntos
Diálise Peritoneal , Ultrafiltração , Humanos , Icodextrina , Projetos Piloto , Estudos Retrospectivos , Glucanos , Glucose , Peritônio , Soluções para Diálise
17.
PLoS One ; 17(10): e0276786, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36315567

RESUMO

The resistance and the birth of new intrinsic and multidrug-resistant pathogenic species like C. auris is creating great concern in the antifungal world. Given the limited drug arsenal and the lack of effectiveness of the available compounds, there is an urgent need for innovative approaches. The murine mAb 2G8 was humanized and engineered in silico to develop a single-chain fragment variable (hscFv) antibody against ß-1,3-glucans which was then expressed in E. coli. Among the recombinant proteins developed, a soluble candidate with high stability and affinity was obtained. This selected protein is VL-linker-VH oriented, and it is characterized by the presence of two ubiquitin monomers at the N-terminus and a His tag at the C-terminus. This construct, Ub2-hscFv-His, guaranteed stability, solubility, efficient purification and satisfactory recovery of the recombinant product. HscFv can bind ß-1,3-glucans both as coated antigens and on C. auris and C. albicans cells similarly to its murine parental and showed long stability and retention of binding ability when stored at 4°, -20° and -80° C. Furthermore, it was efficient in enhancing the antifungal activity of drugs caspofungin and amphotericin B against C. auris. The use of biological drugs as antifungals is limited; here we present a promising hscFv which has the potential to be useful in combination with currently available antifungal drugs.


Assuntos
Antifúngicos , Micoses , Camundongos , Animais , Antifúngicos/farmacologia , Escherichia coli , Anfotericina B , Glucanos , Testes de Sensibilidade Microbiana
18.
Food Res Int ; 161: 111785, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192936

RESUMO

Pullulan-Jiuzao glutelin (JG) conjugates (PJCs) were prepared via Maillard reaction in this study. PJCs were prepared by optimizing pullulan to JG ratios (0.5:1, 1:1, 2:1, and 4:1, expressed as PJC-0.5, PJC-1, PJC-2, and PJC-4, respectively) and reaction times (0-180 min) at pH 7 and 11. The secondary structure changes of PJC compared to JG, potential conjugation sites between pullulan and JG, PJC emulsifying properties, in vitro antioxidant activities, and interaction with curcumin (CUR) were investigated. Among the four PJCs, PJC-2 obtained after 180 min reaction at pH 11 and 90 °C exhibited the best ability in nano-emulsion stabilization with the lowest particle size (180-200 nm and 290-450 nm against NaCl during storage), PDI (0.2-0.4 and 0.4-0.7 against NaCl during storage), highest zeta-potential (-20.10 mV), and lowest backscattering intensity. The spontaneous conjugation binding sites between pullulan and JG were Arg-39, Arg-54, and Asp-168. In contrast to native JG, PJC-2 exhibited better antioxidant capacities, low toxicity for CCD 841 CON and Caco-2 cells, and enhancement of antioxidant enzyme content (i.e., SOD, GPX, and CAT) after AAPH-induced oxidative stress. In addition, there exists an interaction between CUR and PJC-2 by residues Ala-74, Asp-376, Arg-368 and -374, Val-45, and Ala-44 of JG. The results above exhibit important implications for the fabrication of PJC-stabilize nano-emulsion and even for developing PJC product as a potential carrier of CUR in the functional food industry.


Assuntos
Curcumina , Antioxidantes/química , Antioxidantes/farmacologia , Células CACO-2 , Curcumina/química , Curcumina/farmacologia , Emulsões/química , Glucanos , Glutens , Humanos , Cloreto de Sódio , Superóxido Dismutase
19.
Front Immunol ; 13: 1015586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248898

RESUMO

Meningitis due to the fungal pathogen Cryptococcus neoformans is estimated to cause nearly 200,000 deaths annually, mostly in resource-limited regions. We previously identified cryptococcal protein antigens which, when delivered in glucan particles, afford vaccine-mediated protection against an otherwise lethal infection. Many of these proteins exhibit significant homology to other similar cryptococcal proteins leading us to hypothesize that protection may be augmented by immunologic cross-reactivity to multiple members of a protein family. To examine the significance of protein cross-reactivity in vaccination, we utilized strains of Cryptococcus that are genetically deficient in select antigens, yet are still lethal in mice. Vaccination with a protein without homologs (e.g., Mep1 and Lhc1) protected against challenge with wild-type Cryptococcus, but not against a deletion strain lacking that protein. Contrastingly, vaccination with a single chitin deacetylase (Cda) protein protected against the corresponding deletion strain, presumably due to host recognition of one or more other family members still expressed in this strain. Vaccination with a single Cda protein induced cross-reactive antibody and interferon-gamma (IFNγ) immune responses to other Cda protein family members. Paradoxically, we saw no evidence of cross-protection within the carboxypeptidase family of proteins. Factors such as in vivo protein expression and the degree of homology across the family could inform the extent to which vaccine-mediated immunity is amplified. Together, these data suggest a role for prioritizing protein families in fungal vaccine design: increasing the number of immune targets generated by a single antigen may improve efficacy while diminishing the risk of vaccine-resistant strains arising from gene mutations.


Assuntos
Criptococose , Cryptococcus neoformans , Amidoidrolases , Animais , Antígenos de Fungos , Modelos Animais de Doenças , Glucanos , Interferon gama , Camundongos
20.
Colloids Surf B Biointerfaces ; 220: 112934, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36265313

RESUMO

A series of biotinylated ß-cyclodextrin grafted pullulan (Bio-CDPu) for liver-specific drug delivery were synthesized and characterized by Fourier transform infrared (FTIR) and hydrogen nuclear magnetic resonance (1H NMR) spectroscopy, and then their self-assembled spherical nanoparticles (NPs) with 110-200 nm diameter were prepared. Doxorubicin (DOX) was selected as an anti-cancer model drug to prepare the drug-loaded NPs, and the drug loading efficiency (LE%) and loading content (LC%) were determined. The drug release behavior in vitro of DOX/Bio-CDPu NPs exhibited sustained release. The results of methyl thiazolyl tetrazolium (MTT) assays, confocal laser scanning microscopy (CLSM) observations and flow cytometric (FCM) analysis indicated that the designed Bio-CDPu nanocarriers showed good cytocompatibility with Bel-7404 cells and high cellular uptake. Due to their rich biotin /or pullulan ligands, Bio-CDPu NPs could promote DOX to enter Bel-7404 cells and inhibit the tumor cell growth. After intravenous injection to rats, DOX/Bio-CDPu NPs solution exhibited increased area under the curve (AUC) and prolonged half life time (t1/2), meanwhile, the drug concentration in the liver was significantly increased, and the cardio-renal toxicity was reduced. Furthermore, DOX/Bio-CDPu NPs exhibited a better anti-tumor therapeutic effect on tumor-bearing mice. Therefore, Bio-CDPu NPs can be chosen as a potential high-efficiency liver targeted carrier.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , beta-Ciclodextrinas , Ratos , Camundongos , Animais , Doxorrubicina/química , Glucanos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Fígado , Portadores de Fármacos/uso terapêutico
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