Potential of natural polysaccharide for ovarian cancer therapy
Ovarian cancer, characterized by high lethality, presents a significant clinical challenge. The standard first-line treatment is surgery and chemotherapy; however, postoperative chemotherapy is often ineffective and associated with severe side effects and the development of drug resistance. Consequently, there is an urgent need for innovative drug delivery strategies to enhance therapeutic efficacy. Natural polysaccharide polymers with high bioactivity have been extensively investigated for use alone or as adjuvants to chemotherapy and radiotherapy, and also for the preparation of efficient delivery systems for ovarian cancer therapy. This paper aims to review recent advances in the application of natural polysaccharides, including hyaluronic acid, chitosan, alginate, and cellulose, in the therapy of ovarian cancer. This paper primarily discusses the anti-tumor properties inherent to these natural polysaccharide polymers and offers a summary of their role in delivery systems used in ovarian cancer therapy.
A deep eutectic solvent with bifunctional acid sites treatment to upgrade a bamboo kraft pulp into a cellulose-acetate grade dissolving pulp
Valorization of non-wood pulp, such as bamboo bleached kraft pulp into high-purity cellulose acetate (CA)-grade dissolving pulp is crucial but challenging in China. Herein, a series of metal salt-based deep eutectic solvents (MSDESs) involving various ZnCl-urea (U), ZnCl-glycerol (G), and ZnCl-lactic acid (LA) are comparatively investigated for this purpose. Thanks to the bifunctional acid sites of Lewis acid ZnCl and Brønsted acid LA, the ZnCl-LA MSDES has the highest acidity (2.62) and interaction affinity to bamboo fibers, leading to the highest efficiency in simultaneous pulp purification and activation. As a result, the resultant upgraded pulp from ZnCl-LA (DES3-F) features remarkable improvements in purity (from 80.8 % to 93.1 %), intrinsic viscosity (from 897 to 419 mg/L), and reactivity (from 18.1 % to 80.8 %). Moreover, the modified acetate product has a high degree of substitution of 2.84 and a yield of 75.5 %. In short, such a proposed MSDES treatment can offer a promising and alternative approach for the manufacture of high-quality dissolving pulp and its derivatives.
Loss-of-function of SSIIa and SSIIIa confers high resistant starch content in rice endosperm
Rice (Oryza sativa L.) endosperm accumulates huge amounts of starch. Rice starch is highly digestible, potentially enhancing the occurrence of blood sugar- and intestine-related diseases such as type 2 diabetes. Resistant starch (RS) is hardly digestible in small intestine but can be converted into beneficial short-chain fatty acids in large intestine, potentially reducing the incidence of these diseases. However, it is still difficult to produce a high RS rice variety. Here, we report that simultaneous deficiency of soluble starch synthases IIa and IIIa confers high RS content in rice endosperm. The ssIIa ssIIIa exhibited higher RS content than did the ssIIIa ssIIIb, a mutant reported currently to have remarkably higher RS content than parental ssIIIa, under our experimental conditions. Loss-of-function of SSIIa and SSIIIa significantly elevated the activity of granule-bound starch synthase I and thus content of amylose. Furthermore, total lipid content increased in mutant seeds, implying that intermediate metabolites spilled out from starch biosynthesis into lipid biosynthesis. The increased amylose content and improved lipid synthesis coordinately contributed to high RS content in mutant seeds. These results further reveal the molecular mechanism of RS occurrence in rice endosperm and provide a critical genetic resource for breeding higher RS rice cultivars.
Stabilizing effect of Leuconostoc mesenteroides Lm10 produced dextran in situ on stirred soy yogurt: Structure-function relationship
Stirred soy yogurt as a dairy alternative is widely accepted among consumers, but its poor stability has been an urgent problem. We found that Leuconostoc mesenteroides Lm10 produced dextran reduced water mobility and improved the water holding capacity of stirred soy yogurt, especially with over 4 % sucrose added which could completely prevent whey separation. With the increase of dextran content, the particle size of stirred soy yogurt was significantly decreased, accompanied by the improvement of viscoelastic behaviors and resistance to deformation. Moreover, dextran had a stronger ability to maintain the stability of stirred soy yogurt in comparison with gelatin, xanthan and carrageenan during cold storage. The structure-function attributes of this dextran were also revealed. Dextransucrase Gtf1674 was responsible for synthesizing dextran during soy yogurt fermentation. The produced dextran was mainly composed of α-1,6 glycosidic linkages with a low-branched degree and high molecular weight. After stirring, the dextran entangled with soy protein and formed small aggregates with a dense gel structure and small pores, causing them prone to binding with water and reducing the syneresis. This study suggested the benefits of dextran produced by Leuc. mesenteroides Lm10 in stirred soy yogurt, and facilitated developing the "clean label" plant-derived products.
Chitosan nanoparticles of imatinib mesylate coated with TPGS for the treatment of colon cancer: In-vivo & in-vitro studies
The study aimed to develop and evaluate chitosan-based nanoparticles coated with TPGS for the targeted delivery of imatinib mesylate to colon cancer cells. Particle size and zeta potential analysis were within the acceptable range for targeting colon cancer. CS-IMT-TPGS-NPs had a significant positive zeta potential of 30.4 mV, suggesting improved cellular intake. FE-SEM and TEM demonstrated that the nanoparticles appeared spherical, smooth, and did not aggregate, with a visible TPGS coating. XRD confirmed that crystalline imatinib transitioned to an amorphous state during nano formulation. In-vitro tests on HCT-116 cells demonstrated that CS-IMT-TPGS-NPs outperformed free IMT regarding cytotoxicity, apoptosis induction, cellular uptake, and cell migration inhibition. Additionally, the nanoparticles were examined in vitro using mitochondrial membrane potential, DNA fragmentation, GAPDH relative gene expression, ROS estimation, and cell cycle analysis. The effect of therapy on expected colon-associated bacterial strains was also investigated. The biocompatibility of nanoparticles was assessed by hemolysis and platelet aggregation experiments. The anti-inflammatory impact was determined using the HET-CAM test. Non-Fickian diffusion at pH 5.5 resulted in sustained in-vitro drug release, with no initial burst. In-vivo investigations using albino Wistar rats suggest pharmacokinetic properties for produced nanoparticles, whereas histopathological examinations assess acute toxicity.
Chromatography-free synthesis of 2,2-disulfonated β-cyclodextrin for regiospecific di-substitution
Cyclodextrins and their derivatives have extensive applications across pharmaceuticals, cosmetics, and the food industry due to their unique hydrophobic cavities. While monosubstituted cyclodextrin derivatives have established synthesis protocols, di-substituted derivatives pose significant challenges, including low yields and complex purification processes. This study presents a novel methodology for synthesizing di-substituted cyclodextrin derivatives, achieving a 33 % yield without relying on chromatographic techniques. This new approach streamlines the synthesis and purification process, making it more practical for large-scale applications and enhancing the utility of cyclodextrin derivatives in various industries.
Chitosan-melanin complex microsphere: A potential colonic delivery system for protein drugs
The characteristics and performance of chitosan-based colon delivery systems are significantly influenced by the method of preparation. Insect chitosan-melanin complex (CMC) may offer superior attributes over traditional shrimp and crab chitosan (CS) for colon-targeted administration. This study used dung beetle CMC as the carrier matrix and comprehensively examined the impact of various crosslinking techniques on the colonic drug delivery efficacy of microspheres, encompassing drug loading, swelling, drug release behavior, adhesion, enzymatic degradation, and absorption enhancement. The results indicate that F-TPPLC microspheres, crosslinked with a combination of formaldehyde and sodium tripolyphosphate, exhibit superior drug loading capabilities, optimal swelling behavior, and controlled in vitro drug release profiles in the colonic environment, along with excellent adhesion and enzymatic degradation properties within intestinal tract. Notably, these F-TPPLC microspheres increase paracellular permeability, possibly by disrupting the calcium-dependent adhesion junctions. In comparison to commercial CS, CMC demonstrates superior drug encapsulation efficiency, enhanced colonic drug release, adhesion, and absorption promotion, rendering it a favorable candidate as a carrier in colon-targeted drug delivery systems. Consequently, F-TPPLC microspheres derived from CMC are highly suitable for colon drug delivery applications and show promising potential for the oral delivery of peptide and protein-based therapeutics to the colon.
Bioinspired mineralization of ultra-small ceria on cellulose nanofiber enables biocompatible and efficient nanozyme
The escalating threat of antibiotic-resistant bacteria necessitates the exploration of alternative therapeutic strategies. Mimicking natural enzymes with artificial nanomaterials to release reactive oxygen species offers an attractive approach but is still challenged by limited catalytic activity, high production costs, and compromised biocompatibility. This work develops a bioinspired mineralization strategy for immobilizing high-density and ultra-small ceria nanoparticles onto cellulose nanofibers. The high surface-to-volume ratio of as-prepared nanoceria coupled with the aqueous processing environment facilitates the incorporation of a high Ce content, significantly enhancing the peroxidase-like activity. The resulting ceria nanozyme demonstrates efficient antibacterial activity with negligible cytotoxicity. The utilization of bio-based resources and a sustainable mineralization procedure allows for the cost-effective, facile preparation of eco-friendly nanozyme products under mild conditions. This study presents a promising strategy for the rational design and large-scale fabrication of high-performance and low-cost bio-based catalysts applicable to diverse targeted catalytic applications.
Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing
Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated HO (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated HO, NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing.
Regioselective functionalization of cellulose nanomaterial for advanced application
Cellulose nanomaterials (CNMs) with their remarkable properties and abundant natural sources have emerged as a versatile platform for material science. However, their widespread adoption to develop novel applications often hinges on precise control over their surface chemistry. Regioselective functionalization, i.e., the ability to modify specific hydroxy groups on the cellulose backbone or aldehyde reducing end group (REG), offers unparalleled control on their surface chemistry. This review highlights the exciting developments in regioselective functionalization of CNMs and their impacts on structure-property relationships. Key factors that influence regioselectivity are examined and exciting applications of regioselectively functionalized CNMs are reviewed. This review also highlights the need for efficient, large-scale regioselective functionalization techniques and identifies key areas for future research.
Structural analysis and accelerating wound healing function of a novel galactosylated glycosaminoglycan from the snail Helix lucorum
Diabetic foot ulcers (DFUs) as a nonhealing wound remain a clinical challenge, and the development of pro-healing and cost-effective drugs is in urgent need. Herein, we reported a novel galactosylated glycosaminoglycan (GAG) from the snail Helix lucorum, as an effective pro-healing compound. The snail GAG is composed of a heparan sulfate-like main chain and galactose side chains at C-3 of GlcNAc residue. Its main chain has a repeating disaccharide structure of → 4)-α-D-GlcNAc-(1 → 4)-α-L-IdoA(1 →. This is the first example of glycosaminoglycan with galactose branches from mollusks. Pharmacological experiments showed that the H. lucorum GAG significantly promoted skin wound healing in both healthy and diabetic mice by accelerating granulation tissue regeneration, angiogenesis, and collagen deposition. The distinctive galactosylated substitution may play an important role on its pro-healing activity. Our discovery enriches the diversity of non-anticoagulant heparan sulfate-like glycosaminoglycans, and provides a potential candidate of pro-healing drug for treating diabetic wound.
Correlation analysis of starch molecular structure and film properties via rearrangements of glycosidic linkages by 1,4-α-glucan branching enzyme
The functional characteristics of starch films are significantly influenced by the amylose content and the distribution of the amylopectin chain length. This work used 1,4-α-glucan branching enzyme to molecularly reconstruct corn, pea, and cassava starch in order to examine the association. Films made of both natural and enzyme-modified starch were produced using the casting method. The study investigated the variations in starch films properties and explored the relationship between starch molecular structure and film qualities by correlation analysis. The results showed a significant positive connection (r = 0.954) between the tensile strength and amylose content, as well as a positive correlation (r = 0.939) between the A chains and the elongation at break. The average chain length (r = 0.932) and amylose content (r = 0.902) showed a positive correlation with the degradation temperature, whereas the amylose content (r = -0.946) showed an adverse correlation with the transparency. The B3 chain (r = 0.851) and the average chain length (r = 0.839) both exhibited a positive connection with its contact angle. As a result, our study thoroughly assesses how starch structure affects the characteristics of starch films and offers a fundamental modification pathway for the development of new application areas.
Contents and structures of branched and linear maltodextrins, malto-oligosaccharides, and sugars in the early developmental stage of phosphorylase1 mutant endosperm of rice
Biochemical analysis of plastidial phosphorylase (Pho1)-deficient mutants of rice strongly suggests that Pho1 plays an important role in the initiation of starch biosynthesis in the endosperm. The present study examined structures and amounts of maltodextrins, malto-oligosaccharides (MOS) as well as sugars in maturing rice endosperm and compared between a pho1-mutant line EM633 and its wild-type cultivar Taichung-65 (TC65). By using a gel permeation HPLC from developing rice endosperm of both lines, branched maltodextrins (BMD) with distinct fine structure could be isolated for the first time, a possible intermediate in the initiation process of starch biosynthesis, whereas its amount was much lower than starch content in both endosperms. This suggests that BMD as a main intermediate in the de novo synthesis of starch molecules is kept to be at a very low level during starch biosynthesis. The amounts of maltose, and MOS as well as linear maltodextrins (LMD) were greatly increased by the pho1 mutation. These results indicate that Pho1 would play an essential role in the step of mobility of maltose to MOS and then to LMD in the de novo synthesis of amylopectin molecules in developing rice endosperm.
Electro-responsive hyaluronic acid-based click-hydrogels for wound healing
With the aim of healing challenging skin wounds, electro-responsive click-hydrogels made of hyaluronic acid (clickHA) crosslinked with a modified polyethylene glycol precursor (PEG) were prepared by semi-interpenetrating a conducting polymer, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) by oxidative polymerization. The porosity and pore size of the mixed hydrogel, clickHA/PEDOT-MeOH, were both higher than those determined for the hydrogel without PEDOT-MeOH, while a honeycomb-like morphology with PEDOT-MeOH covering the pore walls was observed. Although such PEDOT-MeOH-induced changes did not influence the water absorption capacity of clickHA, they drastically affected the mechanical and electrochemical behavior. More specifically, the semi-interpenetration of PEDOT-MeOH into clickHA resulted in an increase of the Young's modulus, the compressive strength and, especially, the electrochemical activity. The biocompatibility and the potential for skin regeneration of clickHA/PEDOT-MeOH were preliminary assessed using viability and wound-healing assays with epithelial cells. Not only is the conducting hydrogel formulation biocompatible, but also promotes efficient cell migration by electrostimulation using a small voltage (0.5 V) for a short time (15 min). Thus, in just 1 h the wound gap was repaired, and a homogeneous monolayer of migrated cells was formed.
Intelligent microneedle patch based on functionalized alginate and chitosan for long-term self-regulated insulin delivery
Severely diabetic patients need insulin input to maintain the body's glycemic balance. However, traditional injection methods are often associated with poor adherence and an increased risk of hypoglycemia. Microneedle technology offers a promising solution by minimizing pain and trauma during insulin administration. Nonetheless, achieving prolonged glycemic control by microneedle with high insulin loading remains a significant challenge. Herein, we introduce an innovative microneedle patch that draws inspiration from the elegant light-induced blooming of water lily petals. The patch features a glucose-responsive hydrogel network crafted from two modified polysaccharide polymers, which enables the delivery of long-acting insulin without depending on glucose oxidase. By incorporating phenylboronic acid-modified sodium alginate, quaternary ammonium chitosan, and polyvinyl alcohol into a hydrogel matrix, we have created a microneedle system that harbors dynamic borate ester linkages and electrostatic attractions, resulting in heightened sensitivity to blood glucose levels. The electrostatic interaction acts as a relatively stable crosslinking point, balancing the dynamic reproducibility response based on the borate ester bond. This self-adaptive hydrogel can regulate insulin-controlled release by responding to changes in glucose concentration. Herein, we achieved massive insulin loading (20 IU) with long lasting glycaemic control (48 h) in a single treatment of diabetic SD rats.
Natural cellulose reinforced multifunctional eutectogels for wearable sensors and epidermal electrodes
Wearable electronics significantly impact health monitoring, clinical care, and human-machine interfaces. Eutectogels, which utilize deep eutectic solvents (DES) address the drawbacks of hydrogels, such as weight loss and poor temperature tolerance, as well as the high costs and toxicities associated with ionogels. Despite these advances, most eutectogels serve only as sensors or epidermal electrodes and rarely fulfill both functions simultaneously. In this study, we present a multifunctional eutectogel designed to function in both ways. Incorporating natural cotton cellulose nanofibers as nanofillers reinforced the tensile strength of the resultant eutectogel by 7.47 times compared to that of the pure eutectogel, reaching 4.93 MPa. This eutectogel exhibited high ionic conductivity (1.22 S m), strong adhesion (1562.2 kPa to iron), self-healing ability (80.37% strain recovery and 80.53% tensile strength recovery), a broad temperature tolerance (-40 to 80 °C), and antibacterial properties. It demonstrates high sensitivity for the real-time strain detection of human activities and accurately captures electrophysiological signals, enabling the control of a small car. This versatile eutectogel has excellent potential for use in flexible wearable electronics.
Mutation of MeMinD increased amyloplast size with a changed starch granule morphologenesis and structures in cassava storage roots
Amyloplasts are the sites of starch synthesis and accumulation. Little is known about amyloplast division and its effects on the size, structure, and physicochemical properties of starch granules. In this study, we created mutants of plastid division-related gene MeMinD by CRISPR/Cas9 technology, leading to the disruption of normal division of amyloplasts in cassava storage roots. The memind mutants exhibited significantly enlarged amyloplasts with an increased number of starch granules, and broader range of granule sizes. The loss of MeMinD function led to transcriptional reprogramming of gene expressions related to starch-synthesizing enzymes, affecting the fine structure of starch. Starch in memind mutant storage roots showed a significantly decreased proportion of shorter amylopectin chains and an increased proportion of medium and long chains, which ultimately led to a significant increase in apparent amylose content (AAC) in memind mutants compared to that in WT. The changes in starch granule size and structure resulted in a significant increase in onset temperature (To), peak temperature (Tp), and conclusion temperature (Tc) of the gelatinization process, extending the time to reach peak temperature. These data suggest that regulating amyloplast division affects starch accumulation in cassava, presenting an effective strategy for developing novel cassava starch.
Novel food-grade water-in-water emulsion fabricated by amylopectin and tara gum: Property evaluation and stability analysis
To surmount the limitation of the instability of the currently reported water-in-water (W/W) emulsions, novel W/W emulsionss were constructed using amylopectin (AMP) and tara gum (TG) as the phases, and differently shaped ovalbumin (OVA) particles were used as stabilizers to improve the stability of W/W emulsions. Experiments displayed that the conformation of OVA could be changed by heating treatment, thus forming fibrous or spherical OVA particles that had the potential to stabilize TG-in-AMP (TG/AMP) emulsions. The emulsions had the best stability when the pH was 4 and the concentration of OVA particles was 3 %. Moreover, since ovalbumin fibril (OVAF) had better adsorption at the water-water interface than ovalbumin sphere (OVAS), OVAF-stabilized TG/AMP emulsion (OF-TE) had a relatively denser interfacial layer and exhibited more satisfactory ionic stability and physical stability than OVAS-stabilized TG/AMP emulsion (OS-TE). The rheological results demonstrated that OVAF and OVAS had little effect on the viscosity of TG/AMP emulsions. In brief, OVAF was more effective in improving the stability of TG/AMP emulsions than OVAS, and OF-TE did not show phase separation for at least 5 days. This study may be of great significance in improving the stability of food-grade W/W emulsions.
Acidic dimethyl sulfoxide: A solvent system for the fast dissolution of pectin derivatives suitable for subsequent modification
This study investigates the use of dimethyl sulfoxide (DMSO) as a solvent for the dissolution and subsequent chemical modification of various pectin derivatives. DMSO was found to effectively dissolve low-methoxy pectin, high-methoxy pectin, polygalacturonic acid hydrazide, pectin amide, and polygalacturonic hydroxamic acid when the negative charges on the polysaccharide backbone were neutralized with organic acids. The dissolution process was further enhanced by increasing the temperature, although higher temperatures also promoted chain cleavage. The dissolved pectin derivatives were successfully modified through transesterification and Schiff base formation, demonstrating the potential of acidic DMSO as a non-toxic and cost-effective solvent system for homogeneous pectin chemistry. The study opens new possibilities for the functionalization of pectin in various industrial and biomedical applications.
Wheat arabinoxylans: Insight into structure-function relationships
Arabinoxylan (AX), a key non-starch polysaccharide found in the cell walls of cereals like wheat, holds significant importance in the food industry. Recently, it has attracted attention due to its numerous health benefits. While the benefits of wheat arabinoxylans are well-established, a more comprehensive understanding of the relationship between their structure and functional properties is essential. This knowledge will be instrumental in addressing potential concerns in future research focusing on food products containing wheat arabinoxylan. Previous reviews predominantly focused on cereal arabinoxylans, and only a few have addressed wheat arabinoxylan. This review aims to consolidate recent research findings on wheat arabinoxylans, highlighting their health benefits and potential links to structural variations. This will aid future studies in this area. Feruloylated arabinoxylans and arabinoxylan oligosaccharides stand out as the most known for their health benefits. Modifying the chemical structure of arabinoxylans to yield low molecular weight oligosaccharides enhances their immunomodulatory and antioxidant activities, as well as promotes the growth and availability of beneficial gut microbes. The antioxidant activity is positively correlated with the ferulic acid content, whereas it has a negative correlation with arabinose substitution. Nevertheless, additional research using final products is necessary to delve into the potential underlying mechanisms.
Recent advances in 3D bioprinted polysaccharide hydrogels for biomedical applications: A comprehensive review
Polysaccharide hydrogels, which can mimic the natural extracellular matrix and possess appealing physicochemical and biological characteristics, have emerged as significant bioinks for 3D bioprinting. They are highly promising for applications in tissue engineering and regenerative medicine because of their ability to enhance cell adhesion, proliferation, and differentiation in a manner akin to the natural cellular environment. This review comprehensively examines the fabrication methods, characteristics, and applications of polysaccharide hydrogel-driven 3D bioprinting, underscoring its potential in tissue engineering, drug delivery, and regenerative medicine. To contribute pertinent knowledge for future research in this field, this review critically examines key aspects, including the chemistry of carbohydrates, manufacturing techniques, formulation of bioinks, and characterization of polysaccharide-based hydrogels. Furthermore, this review explores the primary advancements and applications of 3D-printed polysaccharide hydrogels, encompassing drug delivery systems with controlled release kinetics and targeted therapy, along with tissue-engineered constructs for bone, cartilage, skin, and vascular regeneration. The use of these 3D bioprinted hydrogels in innovative research fields, including disease modeling and drug screening, is also addressed. Despite notable progress, challenges, including modulating the chemistry and properties of polysaccharides, enhancing bioink printability and mechanical properties, and achieving long-term in vivo stability, have been highlighted.