Modification of the Antibiotic, Colistin, with Dextrin Causes Enhanced Cytotoxicity and Triggers Apoptosis in Myeloid Leukemia.

Introduction: Acute myeloid leukemia (AML) remains difficult to treat due to its heterogeneity in molecular landscape, epigenetics and cell signaling alterations. Precision medicine is a major goal in AML therapy towards developing agents that can be used to treat patients with different 'subtypes' in combination with current chemotherapies. We have previously developed dextrin-colistin conjugates to combat the rise in multi-drug resistant bacterial infections and overcome dose-limiting nephrotoxicity. Recent evidence of colistin's anticancer activity, mediated through inhibition of intracellular lysine-specific histone demethylase 1 (LSD1/KDM1A), suggests that dextrin-colistin conjugates could be used to treat cancer cells, including AML. This study aimed to evaluate whether dextrin conjugation (which reduces in vivo toxicity and prolongs plasma half-life) could enhance colistin's cytotoxic effects in myeloid leukemia cell lines and compare the intracellular uptake and localization of the free and conjugated antibiotic. Results: Our results identified a conjugate (containing 8000 g/mol dextrin with 1 mol% succinoylation) that caused significantly increased toxicity in myeloid leukemia cells, compared to free colistin. Dextrin conjugation altered the mechanism of cell death by colistin, from necrosis to caspase 3/7-dependent apoptosis. In contrast, conjugation via a reversible ester linker, instead of an amide, had no effect on the mechanism of the colistin-induced cell death. Live cell confocal microscopy of fluorescently labelled compounds showed both free and dextrin-conjugated colistins were endocytosed and co-localized in lysosomes, and increasing the degree of modification by succinoylation of dextrin significantly reduced colistin internalization. Discussion: Whilst clinical translation of dextrin-colistin conjugates for the treatment of AML is unlikely due to the potential to promote antimicrobial resistance (AMR) and the relatively high colistin concentrations required for anticancer activity, the ability to potentiate the effectiveness of an anticancer drug by polymer conjugation, while reducing side effects and improving biodistribution of the drug, is very attractive, and this approach warrants further investigation.

Structural characteristics and emulsifying properties of linear dextrin/eicosapentaenoic acid composites: Effect of the degree of polymerization.

This work aimed at building functional emulsions based on the linear dextrins (LDs) emulsion system. The gradient polyethylene glycol (PEG) precipitaion method was used to fractionate LDs into fractions with different degrees of polymerization (DP). A package, and co-precipitation procedure of LDs, and eicosapentaenoic acid (EPA) was used to fabricate LDs-EPA composites. The gas chromatograph, Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimetry analyses affirmed the formation of the LDs-EPA composites. The sizes of these composites were 38.55 nm, 59.14 nm to 80.62 nm, respectively, and they had good amphiphilicity. Compared with LDs, these LDs-EPA composites stabilized Pickering emulsion had higher stability and antioxidant capacity. Their emulsifying ability was positively correlated with the DP values of LDs. Furthermore, the oxidation stability results showed that LDsF10-EPA emulsion had the lowest lipid hydroperoxide (LHs) content, malondioxide (MDA) content and hexal concentration, which were 138.75 mmol kg-1 oil, 15.50 mmol kg-1 oil and 3.83 µmol kg-1 oil, respectively. The study provided a new idea and application values for the application of LDs in emulsion.

Effects of Soluble Dextrin Fiber from Potato Starch on Body Weight and Associated Gut Dysbiosis Are Evident in Western Diet-Fed Mice but Not in Overweight/Obese Children.

BACKGROUND: The study investigated the impact of starch degradation products (SDexF) as prebiotics on obesity management in mice and overweight/obese children. METHODS: A total of 48 mice on a normal diet (ND) and 48 on a Western diet (WD) were divided into subgroups with or without 5% SDexF supplementation for 28 weeks. In a human study, 100 overweight/obese children were randomly assigned to prebiotic and control groups, consuming fruit and vegetable mousse with or without 10 g of SDexF for 24 weeks. Stool samples were analyzed for microbiota using 16S rRNA gene sequencing, and short-chain fatty acids (SCFA) and amino acids (AA) were assessed. RESULTS: Results showed SDexF slowed weight gain in female mice on both diets but only temporarily in males. It altered bacterial diversity and specific taxa abundances in mouse feces. In humans, SDexF did not influence weight loss or gut microbiota composition, showing minimal changes in individual taxa. The anti-obesity effect observed in mice with WD-induced obesity was not replicated in children undergoing a weight-loss program. CONCLUSIONS: SDexF exhibited sex-specific effects in mice but did not impact weight loss or microbiota composition in overweight/obese children.

Dextrin-assisted gel electromembrane extraction of chiral drugs: Improving the extraction efficiency and investigation of enantioselectivity of extraction.

The present study investigates the use of dextrins (maltodextrin, ß-cyclodextrin, and hydroxypropyl-ß-cyclodextrin) to improve the efficiency of the agarose-based gel electromembrane extraction technique for extracting chiral basic drugs (citalopram, hydroxyzine, and cetirizine). Additionally, it examines the enantioselectivity of the extraction process for these drugs. To achieve these, dextrins were incorporated into either the sample solution, the membrane, or the acceptor solution, and then the extraction procedure was performed. Enantiomers were separated and analyzed using a capillary electrophoresis device equipped with a UV detector. The results obtained under the optimal extraction conditions (sample solution pH: 4.0, acceptor solution pH: 2.0, gel membrane pH: 3.0, agarose concentration: 3 % w/v, stirring rate: 1000 rpm, gel thickness: 4.4 mm, extraction voltage: 62.3 V, and extraction time: 32.1 min) indicated that incorporating dextrins into either the sample solution, membrane or the acceptor solution enhances extraction efficiency by 17.3-23.1 %. The most significant increase was observed when hydroxypropyl-ß-cyclodextrin was added to the acceptor solution. The findings indicated that the inclusion of hydroxypropyl-ß-cyclodextrin in the sample solution resulted in an enantioselective extraction, yielding an enantiomeric excess of 6.42-7.14 %. The proposed method showed a linear range of 5.0-2000 ng/mL for enantiomers of model drugs. The limit of detection and limit of quantification for all enantiomers were found to be < 4.5 ng/mL and <15.0 ng/mL, respectively. Intra- and inter-day RSDs (n = 4) were less than 10.8 %, and the relative errors were less than 3.2 % for all the enantiomers. Finally, the developed method was successfully applied to determine concentrations of enantiomers in a urine sample with relative recoveries of 96.8-99.2 %, indicating good reliability of the developed method.

Casein/butyrylated dextrin nanoparticles and chitosan stabilized bilayer emulsions as fat substitutes in sponge cakes.

This study aimed to evaluate the potential of the bilayer emulsions stabilized with casein/butyrylated dextrin nanoparticles and chitosan as fat substitutes in preparing low-calorie sponge cakes. Among the different cake groups, the substitution of bilayer emulsions at 60% exhibited comparable baking properties, appearance, texture characteristics and stable secondary structure to fat. The specific volume and height were increased by 36.94% and 22%, respectively, while the cake showed higher lightness (L*) in the cores and softer hardness in the crumb. In addition, the moisture content of cakes was increased while the water activity remained unchanged. These results showed that casein/butyrylated dextrin bilayer emulsion was a potential fat substitute for cake products at the ratio of 60% with the desirable characteristics.

Interfacial engineering method to regulate the performances of bilayer emulsions co-stabilized by casein/butyrylated dextrin nanoparticles and chitosan.

In present study, bilayer emulsions with different interfacial structures stabilized by casein/butyrylated dextrin nanoparticles (CDNP), chitosan (CS) and chitosan nanoparticles (CSNP) were prepared to overcome the limitations of conventional emulsions. The effects of chitosan morphology and incorporation sequences on the bilayer emulsions were examined. Bilayer emulsions prepared with CDNP as the inner layer and CS/CSNP as the outer layer were observed to have smaller droplet sizes (1.39 ± 86.74 um and 1.45 ± 7.87 um). Bilayer emulsions prepared with CDNP as the inner layer and CS as the outer layer exhibited the lowest creaming index (2.38 %) after 14 days of storage, indicating excellent stability. Furthermore, bilayer emulsion prepared with CDNP as the inner layer and CS as the outer layer also exhibited a uniform water distribution, excellent protein oxidative stability, and uniformly distributed droplets by the measurement of Low-field NMR, intrinsic tryptophan fluorescence and laser confocal laser scanning microscopy. These results indicated that the study provided a theoretical basis for the development and design of bilayer emulsions with different interfacial structures. This study also provides a new material for the preparation of delivery systems that protect biologically active compounds. Bilayer emulsions are promising for applications in traditional and manufactured food products.

NIR-Active Gold Dogbone Nanorattles Impregnated in Cationic Dextrin Nanoparticles for Cancer Nanotheranostics.

Theranostic systems, which integrate therapy and diagnosis into a single platform, have gained significant attention as a promising approach for noninvasive cancer treatment. The field of image-guided therapy has revolutionized real-time tumor detection, and within this domain, plasmonic nanostructures have garnered significant attention. These structures possess unique localized surface plasmon resonance (LSPR), allowing for enhanced absorption in the near-infrared (NIR) range. By leveraging the heat generated from plasmonic nanoparticles upon NIR irradiation, target cancer cells can be effectively eradicated. This study introduces a plasmonic gold dogbone-nanorattle (AuDB NRT) structure that exhibits broad absorption in the NIR region and demonstrates a photothermal conversion efficiency of 35.29%. When exposed to an NIR laser, the AuDB NRTs generate heat, achieving a maximum temperature rise of 38 °C at a concentration of 200 µg/mL and a laser power density of 3 W/cm2. Additionally, the AuDB NRTs possess intrinsic electromagnetic hotspots that amplify the signal of a Raman reporter molecule, making them an excellent probe for surface-enhanced Raman scattering-based bioimaging of cancer cells. To improve the biocompatibility of the nanorattles, the AuDB NRTs were conjugated with mPEG-thiol and successfully encapsulated into cationic dextrin nanoparticles (CD NPs). Biocompatibility tests were performed on HEK 293 A and MCF-7 cell lines, revealing high cell viability when exposed to AuDB NRT-CD NPs. Remarkably, even at a low laser power density of 1 W/cm2, the application of the NIR laser resulted in a remarkable 80% cell death in cells treated with a nanocomposite concentration of 100 µg/mL. Further investigation elucidated that the cell death induced by photothermal heat followed an apoptotic mechanism. Overall, our findings highlight the significant potential of the prepared nanocomposite for cancer theranostics, combining effective photothermal therapy along with the ability to image cancer cells.

Integrated Analysis of Gut Microbiome and Adipose Transcriptome Reveals Beneficial Effects of Resistant Dextrin from Wheat Starch on Insulin Resistance in Kunming Mice.

Systemic chronic inflammation is recognized as a significant contributor to the development of obesity-related insulin resistance. Previous studies have revealed the physiological benefits of resistant dextrin (RD), including obesity reduction, lower fasting glucose levels, and anti-inflammation. The present study investigated the effects of RD intervention on insulin resistance (IR) in Kunming mice, expounding the mechanisms through the gut microbiome and transcriptome of white adipose. In this eight-week study, we investigated changes in tissue weight, glucose-lipid metabolism levels, serum inflammation levels, and lesions of epididymal white adipose tissue (eWAT) evaluated via Hematoxylin and Eosin (H&E) staining. Moreover, we analyzed the gut microbiota composition and transcriptome of eWAT to assess the potential protective effects of RD intervention. Compared with a high-fat, high-sugar diet (HFHSD) group, the RD intervention significantly enhanced glucose homeostasis (e.g., AUC-OGTT, HOMA-IR, p < 0.001), and reduced lipid metabolism (e.g., TG, LDL-C, p < 0.001) and serum inflammation levels (e.g., IL-1ß, IL-6, p < 0.001). The RD intervention also led to changes in the gut microbiota composition, with an increase in the abundance of probiotics (e.g., Parabacteroides, Faecalibaculum, and Muribaculum, p < 0.05) and a decrease in harmful bacteria (Colidextribacter, p < 0.05). Moreover, the RD intervention had a noticeable effect on the gene transcription profile of eWAT, and KEGG enrichment analysis revealed that differential genes were enriched in PI3K/AKT, AMPK, in glucose-lipid metabolism, and in the regulation of lipolysis in adipocytes signaling pathways. The findings demonstrated that RD not only ameliorated IR, but also remodeled the gut microbiota and modified the transcriptome profile of eWAT.

Biodegradable Dextrin-Based Microgels for Slow Release of Dual Fertilizers for Sustainable Agriculture.

In this research, we report dextrin-based biodegradable microgels (PDXE MGs) having phosphate-based cross-linking units for slow release of urea and a potential P source to improve fertilization. PDXE MGs (∼200 nm) are synthesized by cross-linking the lauroyl-functionalized dextrin chains with sodium tripolyphosphate. The developed PDXE MGs exhibit high loading (∼10%) and encapsulation efficiency (∼88%) for urea. It is observed that functionalization of PDXE MGs with lauroyl chains slows down the release of urea (90% in ∼24 days) as compared to nonfunctionalized microgels (PDX MGs) (99% in ∼17 days) in water. Further studies of the developed formulation display that Urea@PDXE MGs significantly boost maize seed germination and overall plant growth as compared to pure urea fertilizer. Moreover, analysis of maize leaves obtained from plants treated with Urea@PDXE MGs reveals 3.5 ± 0.3% nitrogen content and 90 ± 0.7 mg/g chlorophyll content. These values are significantly higher than 1.4 ± 0.6% nitrogen content and 48 ± 0.05 mg/g chlorophyll content obtained by using bare urea. Further, acid phosphatase activity in roots is reduced upon treatment with PDXE MGs and Urea@PDXE MGs, suggesting the availability of P upon degradation of PDXE MGs by the amylase enzyme in soil. These experimental results present the developed microgel-based biodegradable formulation with a slow release feature as a potential candidate to move toward sustainable agriculture practices.

Characterization of molar mass and conformation of relevant (non-)starch polysaccharides in cereal-based beverages.

Arabinoxylans, ß-glucans, and dextrins influence the brewing industry's filtration process and product quality. Despite their relevance, only a maximum concentration of ß-glucans is recommended. Nevertheless, filtration problems are still present, indicating that although the chemical concentration is essential, other parameters should be investigated. Molar mass and conformation are important polymer physical characteristics often neglected in this industry. Therefore, this research proposes an approach to physically characterize enzymatically isolated beer polysaccharides by asymmetrical flow field-flow fractionation coupled to multi-angle light scattering and differential refractive index detector. Based on the obtained molar masses, root-mean-square radius (rrms from MALS), and hydrodynamic radius (rhyd), conformational properties such as apparent density (ρapp) and rrms/rhyd can be calculated based on their molar mass and size. Consequently, the ρapp and rrms/rhyd behavior hints at the different structures within each polysaccharide. The rrms/rhyd 1.2 and high ρapp values on low molar mass dextrins (1-2·105 g/mol) indicate branches, while aggregated structures at high molar masses on arabinoxylans and ß-glucans (2·105 -6·106 g/mol) are due to an increase of ρapp and a rrms/rhyd (0.6-1). This methodology provides a new perspective to analyze starch and non-starch polysaccharides in cereal-based beverages since different physical characteristics could influence beer's filtration and sensory characteristics.

Preliminary assessment of environmental safety (ecosafety) of dextrin-based nanosponges for environmental applications.

The ability to employ waste products, such as vegetable scraps, as raw materials for the synthesis of new promising adsorbing materials is at the base of the circular economy and end of waste concepts. Dextrin-based nanosponges (D_NS), both cyclodextrin (CD) and maltodextrin (MD), have shown remarkable adsorption abilities in the removal of toxic compounds from water and wastewater, thus representing a bio-based low-cost solution which is establishing itself in the market. Nevertheless, their environmental safety for either aquatic or terrestrial organisms has been overlooked, raising concern in terms of potential hazards to natural ecosystems. Here, the environmental safety (ecosafety) of six newly synthesized batches of D_NS was determined along with their full characterization by means of dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transformed infrared spectroscopy with attenuated total reflection (FTIR-ATR) and transmission electron microscopy (SEM). Ecotoxicity evaluation was performed using a battery of model organisms and ecotoxicity assays, such as the microalgae growth inhibition test using the freshwater Raphidocelis subcapitata and the marine diatom Dunaliella tertiolecta, regeneration assay using the freshwater cnidarian Hydra vulgaris and immobilization assay with the marine brine shrimp Artemia franciscana. Impact on seedling germination of a terrestrial plant of commercial interest, Cucurbita pepo was also investigated. Ecotoxicity data showed mild to low toxicity of the six batches, up to 1 mg/mL, in the following order: R. subcapitata > H. vulgaris > D. tertiolecta > A. franciscana > C. pepo. The only exception was represented by one batch (NS-Q+_BDE_(GLU2) which resulted highly toxic for both freshwater species, R. subcapitata and H. vulgaris. Those criticalities were solved with the synthesis of a fresh new batch and were hence attributed to the single synthesis and not to the specific D_NS formulation. No effect on germination of pumpkin but rather more a stimulative effect was observed. To our knowledge this is the first evaluation of the environmental safety of D_ NS. As such we emphasize that current formulations and exposure levels in the range of mg/mL do not harm aquatic and terrestrial species thus representing an ecosafe solution also for environmental applications.

Intersubunit communication in glycogen phosphorylase influences substrate recognition at the catalytic sites.

Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits, each activated by phosphorylation of the serine-14 residue. GP exists in three interconvertible forms, namely GPa (di-phosphorylated form), GPab (mono-phosphorylated form), and GPb (non-phosphorylated form); however, information on GPab remains scarce. Given the prevailing view that the two GP subunits collaboratively determine their catalytic characteristics, it is essential to conduct GPab characterization to gain a comprehensive understanding of glycogenolysis regulation. Thus, in the present study, we prepared rabbit muscle GPab from GPb, using phosphorylase kinase as the catalyst, and identified it using a nonradioactive phosphate-affinity gel electrophoresis method. Compared with the half-half GPa/GPb mixture, the as-prepared GPab showed a unique AMP-binding affinity. To further investigate the intersubunit communication in GP, its catalytic site was probed using pyridylaminated-maltohexaose (a maltooligosaccharide-based substrate comprising the essential dextrin structure for GP; abbreviated as PA-0) and a series of specifically modified PA-0 derivatives (substrate analogs lacking part of the essential dextrin structure). By comparing the initial reaction rates toward the PA-0 derivative (Vderivative) and PA-0 (VPA-0), we demonstrated that the Vderivative/VPA-0 ratio for GPab was significantly different from that for the half-half GPa/GPb mixture. This result indicates that the interaction between the two GP subunits significantly influences substrate recognition at the catalytic sites, thereby providing GPab its unique substrate recognition profile.

Determination of Atropine by HPLC in Plant of Datura by Liquid-Liquid Extraction and Magnet Solid-Phase Extraction.

Atropine is a tropane alkaloid found in abundance in Datura plant. We used two liquid-liquid extraction methods and magnet solid-phase extraction to compare the amount of atropine in these two types of plants (Datura innoxia and Datura stramonium). The surface magnetic nanoparticle Fe3O4 correction with an amine and dextrin, and finally, magnetic solid-phase extraction Fe3O4@SiO2-NH2-dextrin (MNPs-dextrin), was prepared. We determined the effect of significant parameters in the removal step and optimization of atropine measurements with half-fractional factorial design (25-1) and response surface methodology via central composite design. The optimum conditions are for desorption solvent = 0.5 mL methanol and desorption time of 5 min. We obtained an extraction recovery of 87.63% with a relative standard deviation of 4.73% via six frequented measurements on a 1 µg L-1 atropine standard solution based on the optimum condition. Preconcentration factors for MNPs are 81, limit of detection = 0.76 µg L-1 and limit of quantitation = 2.5 µg L-1.

Effects of cluster dextrin encapsulation on the properties and antioxidant stability of fractionated Riceberry protein hydrolysate powder prepared by bromelain.

In this work, the biological properties of fractionated Riceberry bran protein hydrolysate obtained by ultrafiltration (URBPH) were evaluated and the possibility of using cluster dextrin to produce hydrolysate powder by spray-drying was investigated. Fractionation into peptides < 3 kDa was observed to improve antioxidant activity. URBPH < 3 kDa was then freeze-dried (FD-URBPH) and spray-dried (SD-URBPH) at different inlet air temperatures of 100-160 °C. The water solubility and antioxidant activity of FD-URBPH were higher than those of SD-URBPH. Nevertheless, encapsulation of hydrolysate with 10% cluster dextrin and an inlet temperature of 120 °C was also successful in maintaining protein qualities, which showed high 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic (ABTS•+) scavenging activity (89.14%) and water solubility index (92.49%) and low water activity (aw = 0.53). Moreover, encapsulation preserved the antioxidant activity of peptides during gastrointestinal digestion better than the free form. URBPH and its spray-dried microcapsules could be used as bioactive ingredients in functional drinks or foods.

Ex Vivo Colonic Fermentation of NUTRIOSE® Exerts Immuno-Modulatory Properties and Strong Anti-Inflammatory Effects.

NUTRIOSE® (Roquette, Lestrem, France) is a resistant dextrin with well-established prebiotic effects. This study evaluated the indirect effects of pre-digested NUTRIOSE® on host immune response and gut barrier integrity. Fecal samples from eight healthy donors were inoculated in a Colon-on-a-plate® system (ProDigest, Ghent, Belgium) with or without NUTRIOSE® supplementation. Following 48 h fermentation, colonic suspensions were tested in a Caco-2/THP1-Blue™ co-culture system to determine their effects on gut barrier activity (transepithelial electrical resistance) and immune response following lipopolysaccharide stimulation. Additionally, changes in short-chain fatty acid levels (SCFA) and microbial community composition following a 48 h fermentation in the Colon-on-a-plate® system were measured. Across all donors, immune-mediated intestinal barrier damage was significantly reduced with NUTRIOSE®-supplemented colonic suspensions versus blank. Additionally, IL-6 and IL-10 levels were significantly increased, and the level of the neutrophil chemoattractant IL-8 was significantly decreased with NUTRIOSE®-supplemented colonic suspensions versus blank in the co-culture models following lipopolysaccharide stimulation. These beneficial effects of NUTRIOSE® supplementation were likely due to increased acetate and propionate levels and the enrichment of SCFA-producing bacteria. NUTRIOSE® was well fermented by the colonic bacteria of all eight donors and had protective effects on inflammation-induced disruption of the intestinal epithelial barrier and strong anti-inflammatory effects.

Characterization, health benefits, and food applications of enzymatic digestion- resistant dextrin: A review.

Resistant dextrin or resistant maltodextrin (RD), a short-chain glucose polymer that is highly resistant to hydrolysis by human digestive enzymes, has shown broad developmental prospects in the food industry and has gained substantial attention owing to its lack of undesirable effects on the sensory features of food or the digestive system. However, comprehensive fundamental and application information on RD and how RD improves anti-diabetes and obesity have not yet been received. Therefore, the characterization, health benefits and application of RD in various fields are summarized and discussed in the current study. Typically, RD is prepared by the acid thermal method and possesses excellent physicochemical properties, including low viscosity, high solubility, storage stability, and low retro-gradation, which are correlated with its low molecular weight (Mw) and non-digestible glycosidic linkages. In contrast, RD prepared by the simultaneous debranching and crystallization method has low solubility and high crystallinity. The ingestion of RD can positively affect metabolic diseases (diabetes and obesity) in animals and humans by producing short-chain fatty acids (SCFAs), and facilitating the inflammatory response. Moreover, RD has been widely used in the beverage, dairy products, and dessert industries due to its nutritional value and textural properties without unacceptable quality loss. More studies are required to further explore RD application potential in the food industry and its role in the management of different chronic metabolic disorders.

Binding Specificity of a Novel Cyclo/Maltodextrin-Binding Protein and Its Role in the Cyclodextrin ABC Importer System from Thermoanaerobacterales.

Extracellular synthesis of functional cyclodextrins (CDs) as intermediates of starch assimilation is a convenient microbial adaptation to sequester substrates, increase the half-life of the carbon source, carry bioactive compounds, and alleviate chemical toxicity through the formation of CD-guest complexes. Bacteria encoding the four steps of the carbohydrate metabolism pathway via cyclodextrins (CM-CD) actively internalize CDs across the microbial membrane via a putative type I ATP-dependent ABC sugar importer system, MdxEFG-(X/MsmX). While the first step of the CM-CD pathway encompasses extracellular starch-active cyclomaltodextrin glucanotransferases (CGTases) to synthesize linear dextrins and CDs, it is the ABC importer system in the second step that is the critical factor in determining which molecules from the CGTase activity will be internalized by the cell. Here, structure-function relationship studies of the cyclo/maltodextrin-binding protein MdxE of the MdxEFG-MsmX importer system from Thermoanaerobacter mathranii subsp. mathranii A3 are presented. Calorimetric and fluorescence studies of recombinant MdxE using linear dextrins and CDs showed that although MdxE binds linear dextrins and CDs with high affinity, the open-to-closed conformational change is solely observed after α- and ß-CD binding, suggesting that the CM-CD pathway from Thermoanaerobacterales is exclusive for cellular internalization of these molecules. Structural analysis of MdxE coupled with docking simulations showed an overall architecture typically found in sugar-binding proteins (SBPs) that comprised two N- and C-domains linked by three small hinge regions, including the conserved aromatic triad Tyr193/Trp269/Trp378 in the C-domain and Phe87 in the N-domain involved in CD recognition and stabilization. Structural bioinformatic analysis of the entire MdxFG-MsmX importer system provided further insights into the binding, internalization, and delivery mechanisms of CDs. Hence, while the MdxE-CD complex couples to the permease subunits MdxFG to deliver the CD into the transmembrane channel, the dimerization of the cytoplasmatic promiscuous ATPase MsmX triggers active transport into the cytoplasm. This research provides the first results on a novel thermofunctional SBP and its role in the internalization of CDs in extremely thermophilic bacteria.

Electroconductive bioplatform based on dextrin for the immobilization of hemoglobin: Application for electrochemical monitoring of H2O2.

A novel biodegradable dextrin-based nanocomposite, involving polypyrrole (PPy) and hydrophilic dextrin (Dex) (PPy@Dex) was prepared using in-situ radical chemical polymerization technique. The obtained PPy@Dex bionanocomposite was fully characterized by FT-IR, XRD, FESEM, and DSC methods. The exceptional properties such as biocompatibility, high surface area, the proper functional group on the surface, and outstanding electrical conductivity of synthesized bionanocomposite made it a superior candidate over biomolecules immobilization. Electrochemical observations revealed that the PPy@Dex-coated glassy carbon electrode (GCE) demonstrated improved performance, making it a suitable substrate for immobilizing hemoglobin (Hb) and constructing an efficient biosensor. The resulting biosensor, named Hb-PPy@Dex/GCE, exhibited high activity in the reduction of hydrogen peroxide (H2O2). Amperometric examinations demonstrated an extensive linear range from 2 to 350 µM for Hb-PPy@Dex/GCE. The detection limit of the proposed approach was calculated to be 0.54 µM, following the S/N = 3 protocol.

Combined resistant dextrin and low-dose Mg oxide administration increases short-chain fatty acid and lactic acid production by gut microbiota.

The consumption of resistant dextrin improves constipation, while its fermentation and degradation by the intestinal microbiota produce short-chain fatty acids (SCFA) and lactic acid, which have beneficial effects on host metabolism and immunity. Mg oxide (MgO) is an important mineral that is used to treat constipation. Therefore, resistant dextrin and MgO are often administered together to improve constipation. However, limited information is available regarding the effect of this combination on SCFA and lactic acid production. Crl:CD1(ICR) mice were fed a Mg-free diet with 5% resistant dextrin, followed by oral administration of MgO. We collected the cecum contents and measured SCFA and lactic acid levels. Additionally, the human subjects received resistant dextrin and Mg supplements as part of their habitual diet. The results of this study demonstrate that intestinal microbiota cannot promote SCFA and lactic acid production in the absence of Mg. In a mouse model, low doses of MgO promoted the production of SCFA and lactic acid, whereas high doses decreased their production. In humans, the combined consumption of resistant dextrin and Mg supplements increased the production of SCFA and lactic acid. The production of SCFA and lactic acid from dietary fiber may be augmented by the presence of MgO.

Study on enteral nutrient components causing decreased gastric phenytoin absorption.

BACKGROUND: Previously, we revealed that coadministration of particular enteral nutrients (ENs) decreases plasma concentrations and gastric absorption of phenytoin (PHT), an antiepileptic drug, in rats; however, the mechanism has not been clarified. METHODS: We measured the permeability rate of PHT using a Caco-2 cell monolayer as a human intestinal absorption model with casein, soy protein, simulated gastrointestinal digested casein protein (G-casein or P-casein) or simulated gastrointestinal digested soy protein (G-soy or P-soy), dextrin, sucrose, degraded guar gum, indigestible dextrin, calcium, and magnesium, which are abundant in the ENs, and measured the solution's properties. RESULTS: We demonstrated that casein (40 mg/ml), G-soy or P-soy (10 mg/ml), and dextrin (100 mg/ml) significantly decreased the permeability rate of PHT compared with the control. By contrast, G-casein or P-casein significantly increased the permeability rate of PHT. We also found that the PHT binding rate to casein 40 mg/ml was 90%. Furthermore, casein 40 mg/ml and dextrin 100 mg/ml have high viscosity. Moreover, G-casein and P-casein significantly decreased the transepithelial electrical resistance of Caco-2 cell monolayers compared with casein and the control. CONCLUSION: Casein, digested soy protein, and dextrin decreased the gastric absorption of PHT. However, digested casein decreased PHT absorption by reducing the strength of tight junctions. The composition of ENs may affect the absorption of PHT differently, and these findings would aid in the selection of ENs for orally administered PHT.