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1.
4-Deoxy-l-erythro-5-hexoseulose Uronate (DEH) and DEH Reductase: Key Molecule and Enzyme for the Metabolism and Utilization of Alginate.
Kawai, S, Hashimoto, W
Molecules (Basel, Switzerland). 2022;(2)
Abstract
4-Deoxy-l-erythro-5-hexoseulose uronate (DEH), DEH reductase, and alginate lyase have key roles in the metabolism of alginate, a promising carbon source in brown macroalgae for biorefinery. In contrast to the widely reviewed alginate lyase, DEH and DEH reductase have not been previously reviewed. Here, we summarize the current understanding of DEH and DEH reductase, with emphasis on (i) the non-enzymatic and enzymatic formation and structure of DEH and its reactivity to specific amino groups, (ii) the molecular identification, classification, function, and structure, as well as the structural determinants for coenzyme specificity of DEH reductase, and (iii) the significance of DEH for biorefinery. Improved understanding of this and related fields should lead to the practical utilization of alginate for biorefinery.
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2.
Cation complexation by mucoid Pseudomonas aeruginosa extracellular polysaccharide.
Hills, OJ, Smith, J, Scott, AJ, Devine, DA, Chappell, HF
PloS one. 2021;(9):e0257026
Abstract
Mucoid Pseudomonas aeruginosa is a prevalent cystic fibrosis (CF) lung colonizer, producing an extracellular matrix (ECM) composed predominantly of the extracellular polysaccharide (EPS) alginate. The ECM limits antimicrobial penetration and, consequently, CF sufferers are prone to chronic mucoid P. aeruginosa lung infections. Interactions between cations with elevated concentrations in the CF lung and the anionic EPS, enhance the structural rigidity of the biofilm and exacerbates virulence. In this work, two large mucoid P. aeruginosa EPS models, based on β-D-mannuronate (M) and β-D-mannuronate-α-L-guluronate systems (M-G), and encompassing thermodynamically stable acetylation configurations-a structural motif unique to mucoid P. aeruginosa-were created. Using highly accurate first principles calculations, stable coordination environments adopted by the cations have been identified and thermodynamic stability quantified. These models show the weak cross-linking capability of Na+ and Mg2+ ions relative to Ca2+ ions and indicate a preference for cation binding within M-G blocks due to the smaller torsional rearrangements needed to reveal stable binding sites. The geometry of the chelation site influences the stability of the resulting complexes more than electrostatic interactions, and the results show nuanced chemical insight into previous experimental observations.
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3.
A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401.
Ninomiya, K, Yokoyama, T, Hotta, K, Oze, I, Katsui, K, Hata, T, Yoshioka, H, Bessho, A, Hosokawa, S, Kuyama, S, et al
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2021;(9):5237-5244
Abstract
BACKGROUND Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). METHODS Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis. RESULTS Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04). CONCLUSIONS Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm. TRIAL REGISTRATION ClinicalTrials.gov Identifier Registry number: UMIN000013133.
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4.
Alginate modification via click chemistry for biomedical applications.
Deng, Y, Shavandi, A, Okoro, OV, Nie, L
Carbohydrate polymers. 2021;:118360
Abstract
Alginate biopolymers are characterized by favorable properties, of biocompatibility, degradability, and non-toxicity. However, the poor stability properties of alginate have limited its suitability for diverse applications. Recently, click chemistry has generated significant research interest due to its high reaction efficiency, high selectivity for a single product, harmless byproducts, and processing simplicity. Alginate modified using click chemistry enables the production of alginate derivatives with enhanced physical and chemical properties. Herein, we review the employment of click chemistry in the development of alginate-based materials or systems. Various click chemistries were highlighted, including azide and alkyne cycloaddition (e.g. Copper-(I)-catalyzed azide-alkyne cycloaddition (CuAAC), Strain-promoted alkyne-azide cycloaddition (SPAAC)), Diels-Alder reaction (Inverse electron demand Diels-Alder (IEDDA) cycloaddition, Tetrazine-norbornene Diels-Alder reactions), Thiol-ene/yne addition (Free-radical thiol-ene addition click reactions, Thiol-Michael addition click reactions, Thiol-yne addition click reaction), Oxime based click reactions, and other click reactions. Alginate functionalized with click chemistry and its properties were also discussed. The present study shows that click chemistry may be employed in modifying the mechanical strength, biochemical/biological properties of alginate-based materials. Finally, the applications of alginate-based materials in wound dressing, drug delivery, protein delivery, tissue regeneration, and 3D bioprinting were described and the future perspectives of alginates modified with click chemistry, are subsequently presented. This review provides new insights for readers to design structures and expand applications of alginate using click chemistry reactions in a detailed and more rational manner.
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5.
Pectin-Alginate Does Not Further Enhance Exogenous Carbohydrate Oxidation in Running.
Barber, JFP, Thomas, J, Narang, B, Hengist, A, Betts, JA, Wallis, GA, Gonzalez, JT
Medicine and science in sports and exercise. 2020;(6):1376-1384
Abstract
PURPOSE Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin-fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin-fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running. METHODS Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n = 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired CO2 enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute. RESULTS At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min (P = 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min; P = 1.0). No time-treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all, P > 0.05). CONCLUSION To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)-fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.
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6.
Optimization of Chitosan-Alginate Microparticles for Delivery of Mangostins to the Colon Area Using Box-Behnken Experimental Design.
Mulia, K, Singarimbun, AC, Krisanti, EA
International journal of molecular sciences. 2020;(3)
Abstract
Chitosan-alginate microparticles loaded with hydrophobic mangostins present in the mangosteen rind extract have been formulated and optimized for colon-targeted bioactive drug delivery systems. The chitosan-mangostin microparticles were prepared using the ionotropic gelation method with sodium tripolyphosphate as the cross-linking agent of chitosan. The chitosan-mangostin microparticles were then encapsulated in alginate with calcium chloride as the linking agent. The mangostin release profile was optimized using the Box-Behnken design for response surface methodology with three independent variables: (A) chitosan-mangostin microparticle size, (B) alginate:chitosan mass ratio, and (C) concentration of calcium chloride. The following representative equation was obtained: percent cumulative release of mangostins (10 h) = 59.51 - 5.16A + 20.00B - 1.27C - 1.70AB - 5.43AC - 5.04BC + 0.0579A2 + 10.25B2 + 1.10C2. Cumulative release of 97% was obtained under the following optimum condition for microparticle preparation: chitosan-mangosteen particle size < 100 µm, alginate:chitosan mass ratio of 0.5, and calcium chloride concentration of 4% w/v. The alginate to chitosan mass ratio is the statistically significant variable in the optimization of sequential release profile of mangostins in simulated gastrointestinal fluids. Furthermore, a sufficient amount of alginate is necessary to modify the chitosan microparticles and to achieve a complete release of mangostins. The results of this work indicate that the complete release of mangostins to the colon area can be achieved using the chitosan-alginate microparticles as the bioactive delivery system.
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7.
Alternatives to Acid Suppression Treatment for Laryngopharyngeal Reflux.
Huestis, MJ, Keefe, KR, Kahn, CI, Tracy, LF, Levi, JR
The Annals of otology, rhinology, and laryngology. 2020;(10):1030-1039
Abstract
OBJECTIVE Laryngopharyngeal reflux (LPR) and associated symptoms can be refractory to treatment with acid suppressing medication. We investigated the role and evidence for complementary and alternative medicine (CAM) for LPR in this systematic review. REVIEW METHODS Complementary and alternative treatment was defined in this systematic review as any non-acid suppressing medication, treatment, or therapy. A literature search was performed by two authors in consultation with a medical librarian using controlled vocabulary for "complementary and alternative medicine" and "laryngopharyngeal reflux" in the databases PubMed and EMBASE, with supplemental searches with Google Scholar. RESULTS Twenty articles were included in this review for the modalities: alginate, diet modification, prokinetics, respiratory retraining, voice therapy, rikkunshito (RKT), hypnotherapy, and sleep positioning. The studies were analyzed for bias based on the Cochrane criteria for RCTs and Methodological Index for non-RCT (MINORS) criteria for all other studies. For each modality a level of evidence was assigned to the current body of evidence using the GRADE approach. CONCLUSION There is mixed evidence with a high degree of bias and heterogeneity between studies for the modalities presented in the paper. Based on this review, an anti-reflux diet is recommended for all patients and there is some low-quality evidence to support alkaline water. For patients with predominant vocal symptoms there is evidence that supports voice therapy. There is insufficient evidence to recommend prokinetics at this time. For patients with predominant globus symptoms, alginate, RKT, and relaxation strategies may be used in conjunction with acid suppressing medications for symptom relief.
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8.
Astaxanthin Encapsulated in Biodegradable Calcium Alginate Microspheres for the Treatment of Hepatocellular Carcinoma In Vitro.
Zhang, X, Li, W, Dou, X, Nan, D, He, G
Applied biochemistry and biotechnology. 2020;(2):511-527
Abstract
Astaxanthin (AST) has attracted great interests in the scientific world because of its anti-oxidative, anti-inflammatory properties. And biodegradable materials, like chitosan, have been employed as the AST carrier to protect it from degradation and promote its bioavailability. However, the lack of pH responsiveness of these materials usually could not protect AST from the strong acidic gastric juices. In this study, calcium alginate (CA) microspheres, a pH responsive and biodegradable material, were prepared by a modified double emulsion technology and used as the AST encapsulation agent. Experimental results showed that the microparticles formed had a good degree of roundness, dispersity, encapsulation efficiency, and pH responsiveness. Cellular studies demonstrated that AST encapsulated in CA could inhibit hepatoma cells (HepG2 cell line) but it has relatively small or no impact on control hepatocytes (THLE-2 cell line). Furthermore, investigation of the underlying mechanism indicated that recovery of disorder of glucose metabolism by inhibiting aerobic glycolysis and promoting tricarboxylic acid cycle played an important part in the cell proliferation inhibition of hepatoma cells. As suggested above, AST could be a very promising therapeutic agent of liver cancer in clinical trials.
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9.
Duration of adhesion of swallowed alginates to distal oesophageal mucosa: implications for topical therapy of oesophageal diseases.
Sonmez, S, Coyle, C, Sifrim, D, Woodland, P
Alimentary pharmacology & therapeutics. 2020;(3):442-448
Abstract
BACKGROUND We have previously shown, ex vivo, that alginate solutions can have a topical protective effect on oesophageal mucosal biopsies exposed to simulated gastric juice. Oesophageal mucosal impedance can measure the duration of mucosal adherence of ionic solutions since the impedance drops when the solution is present, and rises to baseline as the solution clears. AIM: To investigate the in vivo duration of adhesion of swallowed alginate solution to distal oesophageal mucosa. METHODS We studied 20 healthy volunteers and 10 patients with heartburn. A pH-impedance catheter was inserted, and baseline distal channel oesophageal impedance measured. Healthy volunteers received 10 mL of either sodium alginate (Gaviscon Advance), Gaviscon placebo (no alginate) or viscous slurry (saline mixed with sucralose), given in a randomised, single-blinded order over three visits. Patients received either sodium alginate or placebo on two visits. Initial impedance drop was measured, then 1-minute mean impedance was measured each minute until ≥75% recovery to baseline. RESULTS In healthy volunteers, sodium alginate adhered to the oesophageal mucosa for longer than placebo or viscous slurry (10.4 [8.7] minutes vs 1.1 [1.6] vs 3.6 [4.0], P < 0.01). In patients, sodium alginate adhered to the oesophageal mucosa for longer than placebo (9.0 (5.4) vs 3.7 (4.1), P < 0.01). CONCLUSIONS Sodium alginate solution adhered to the oesophageal mucosa for significantly longer than placebo or viscous slurry. This demonstrates that alginates could confer a protective benefit due to mucoadhesion and can be a basis for further development of topical protectants and for topical drug delivery in oesophageal disease.
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10.
Synthesis and assessment of CTAB and NPE modified organo-montmorillonite for the fabrication of organo-montmorillonite/alginate based hydrophobic pharmaceutical controlled-release formulation.
Yan, H, Chen, X, Bao, C, Yi, J, Lei, M, Ke, C, Zhang, W, Lin, Q
Colloids and surfaces. B, Biointerfaces. 2020;:110983
Abstract
The research goal of the present study was to develop a carrier for loading and controlled -release of the hydrophobic drug with the combined use of organo-montmorillonite (OMMT) and alginate. The OMMT was synthesized through the intercalation modification of sodium montmorillonite (Na-MMT) with cationic cetyltrimethylammonium bromide (CTAB), nonionic nonylphenol polyoxyethylene ether (NPE) and the mixture of them via simple and convenient wet ball-milling method. Furthermore, the organo-montmorillonite/alginate (OMMT/Alg) composite hydrogel beads with slow and controlled release properties were constructed by using alginate as a coating material under the exogenous cross-linking of calcium ions. The physical and chemical properties of OMMT were comparatively evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analyzer (TGA), BET-specific surface area measurements, and drug adsorption experiments. Experimental results showed that the presence of CTAB was able to facilitate the intercalation of CTAB/NPE into Na-MMT through the cation exchange reaction. And the cationic CTAB and nonionic NPE were adsorbed or intercalated into the MMT lamellar structure through the wet ball-milling process, which could change the hydrophilic nature of Na-MMT and improve its affinity to the hydrophobic drug molecules. In addition, the OMMT/Alg composite hydrogel beads displayed superior sustained-release properties than Na-MMT/Alg, mainly ascribed to the good affinity of OMMT to hydrophobic drug that retarded the drug diffusion. In particular, CTA/NPE-MMT/Alg with the highest loading capacity (LC) and encapsulation efficiency (EE) revealed the optimal controlled performance for the release of hydrophobic ibuprofen. The release followed the Korsmeyer-Peppas model suggested non-Fickian diffusion release mechanism. Based on the high drug loading capacity and excellent controlled drug release properties, the CTA/NPE-MMT/Alg incorporating hydrophobic drugs into hydrophilic matrices could be a highly promising material for use in hydrophobic drug delivery.