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1.
Mol Biol Rep ; 51(1): 705, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824214

ABSTRACT

BACKGROUND: Quinoa seeds (Chenopodium quinoa Willd.) have gained interest due to their naturally occurring phytochemicals and antioxidants. They possess potent anticancer properties against human colorectal cancer. METHODS AND RESULTS: Fatty acids in quinoa oil were studied using gas chromatography-mass spectrometry. Rats were used to test the acute oral toxicity of the nanoemulsion loaded with sodium alginate. The DPPH radical scavenging method was employed to assess the nanoemulsion's ability to scavenge free radicals. It was examined the in vivo anticancer potential of quinoa oil nanoemulsion on rats with breast cancer induced by 7, 12-dimethylbenz (a) anthracene (DMBA). DMBA-breast cancer models received daily quinoa oil nanoemulsions for 30 days. The anticancer effect of the nanoemulsion was assessed by measuring ROS, protein carbonyl, gene expression of anti-oncogenes, and histopathological analysis. Supplying quinoa oil nanoemulsion significantly reduced the increase in serum ROS and PC levels induced in breast cancer tissue. The expression levels of antioncogenes in breast cancer tissue were decreased by the quinoa oil nanoemulsion. Nanoemulsions also improved the cellular morphology of breast tumors. CONCLUSION: The study results indicate that quinoa oil nanoemulsion has anticancer activity against breast cancer, effectively modulating oxidative stress markers, anti-oncogene expressions, and tissue architecture. It can be inferred from the results that quinoa oil nanoemulsion is a chemoprotective medication that may hinder breast cancer progression in rats.


Subject(s)
Alginates , Breast Neoplasms , Chenopodium quinoa , Emulsions , Plant Oils , Animals , Chenopodium quinoa/chemistry , Female , Rats , Plant Oils/pharmacology , Plant Oils/chemistry , Alginates/chemistry , Alginates/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Antioxidants/pharmacology , Reactive Oxygen Species/metabolism , Nanoparticles/chemistry , Seeds/chemistry , Antineoplastic Agents/pharmacology , Oxidative Stress/drug effects , Humans
2.
J Nanobiotechnology ; 22(1): 305, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822364

ABSTRACT

BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.


Subject(s)
Fibrosis , Gastrointestinal Microbiome , Kidney , Nanoparticles , Rats, Sprague-Dawley , Animals , Gastrointestinal Microbiome/drug effects , Rats , Administration, Oral , Male , Kidney/pathology , Kidney/drug effects , Nanoparticles/chemistry , Microgels/chemistry , Lacticaseibacillus casei , Probiotics/pharmacology , Renal Insufficiency, Chronic/drug therapy , Chitosan/chemistry , Alginates/chemistry , Pentacyclic Triterpenes/pharmacology , Drug Delivery Systems/methods , Tissue Distribution , Cell Wall
3.
Food Res Int ; 188: 114473, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823837

ABSTRACT

Oral delivery of larger bioactive peptides (>20 amino acids) to the small intestine remains a challenge due to their sensitivity to proteolytic degradation and chemical denaturation during gastrointestinal transit. In this study, we investigated the capacity of crosslinked alginate microcapsules (CLAMs) formed by spray drying to protect Plantaricin EF (PlnEF) (C-EF) in gastric conditions and to dissolve and release PlnEF in the small intestine. PlnEF is an unmodified, two-peptide (PlnE: 33 amino acids; PlnF: 34 amino acids) bacteriocin produced by Lactiplantibacillus plantarum with antimicrobial and gut barrier protective properties. After 2 h incubation in simulated gastric fluid (SGF) (pH 1.5), 43.39 % ± 8.27 % intact PlnEF was liberated from the CLAMs encapsulates, as determined by an antimicrobial activity assay. Transfer of the undissolved fraction to simulated intestinal fluid (SIF) (pH 7) for another 2 h incubation resulted in an additional release of 16.13 % ± 4.33 %. No active PlnEF was found during SGF or sequential SIF incubations when pepsin (2,000 U/ml) was added to the SGF. To test PlnEF release in C-EF contained in a food matrix, C-EF was mixed in peanut butter (PB) (0.15 g C-EF in 1.5 g PB). A total of 12.52 % ± 9.09 % active PlnEF was detected after incubation of PB + C-EF in SGF without pepsin, whereas no activity was found when pepsin was included. Transfer of the remaining PB + C-EF fractions to SIF yielded the recovery of 46.67 % ± 13.09 % and 39.42 % ± 11.53 % active PlnEF in the SIF following exposure to SGF and to SGF with pepsin, respectively. Upon accounting for the undissolved fraction after SIF incubation, PlnEF was fully protected in the CLAMs-PB mixture and there was not a significant reduction in active PlnEF when pepsin was present. These results show that CLAMs alone do not guard PlnEF bacteriocin peptides from gastric conditions, however, mixing them in PB protected against proteolysis and improved intestinal release.


Subject(s)
Alginates , Bacteriocins , Capsules , Alginates/chemistry , Peptides/chemistry , Intestine, Small/metabolism , Lactobacillus plantarum/metabolism , Hydrogen-Ion Concentration , Cross-Linking Reagents/chemistry , Pepsin A/metabolism
4.
Carbohydr Polym ; 339: 122209, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823899

ABSTRACT

The escalating global health concern arises from chronic wounds induced by bacterial infections, posing a significant threat to individuals. Consequently, an imperative exist for the development of hydrogel dressings to facilitate prompt wound monitoring and efficacious wound management. To this end, pH-sensitive bromothymol blue (BTB) and pH-responsive drug tetracycline hydrochloride (TH) were introduced into the polysaccharide-based hydrogel to realize the integration of wound monitoring and controlled treatment. Polysaccharide-based hydrogels were formed via a Schiff base reaction by cross-linking carboxymethyl chitosan (CMCS) on an oxidized sodium alginate (OSA) skeleton. BTB was used as a pH indicator to monitor wound infection through visual color changes visually. TH could be dynamically released through the pH response of the Schiff base bond to provide effective treatment and long-term antibacterial activity for chronically infected wounds. In addition, introducing polylactic acid nanofibers (PLA) enhanced the mechanical properties of hydrogels. The multifunctional hydrogel has excellent mechanical, self-healing, injectable, antibacterial properties and biocompatibility. Furthermore, the multifaceted hydrogel dressing under consideration exhibits noteworthy capabilities in fostering the healing process of chronically infected wounds. Consequently, the research contributes novel perspectives towards the advancement of intelligent and expeditious bacterial infection monitoring and dynamic treatment platforms.


Subject(s)
Alginates , Anti-Bacterial Agents , Bandages , Chitosan , Hydrogels , Nanofibers , Wound Healing , Nanofibers/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Hydrogen-Ion Concentration , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Alginates/chemistry , Animals , Staphylococcus aureus/drug effects , Tetracycline/chemistry , Tetracycline/pharmacology , Mice , Wound Infection/drug therapy , Polysaccharides/chemistry , Escherichia coli/drug effects , Schiff Bases/chemistry , Microbial Sensitivity Tests , Humans
5.
Carbohydr Polym ; 339: 122232, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823905

ABSTRACT

In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.


Subject(s)
Alginates , Bone Regeneration , Chitosan , Hydrogels , Polyvinyl Alcohol , Tissue Engineering , Tissue Scaffolds , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Polyvinyl Alcohol/chemistry , Tissue Scaffolds/chemistry , Humans , Bone Regeneration/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Tissue Engineering/methods , Nanotubes, Carbon/chemistry , Osteoblasts/drug effects , Osteoblasts/cytology , Graphite/chemistry , Graphite/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Cell Survival/drug effects , Cell Line
6.
Int J Pharm ; 658: 124225, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38750982

ABSTRACT

High-altitude sleep disturbance is a common symptom of acute mountain sickness, which can be alleviated via modulation of the gut-brain axis. Quercetin (Que) is used to modulate gut microbiota and serves as a potential drug to regulate the gut-brain axis, but the poor solubility and bioavailability affect its biological functions. Here, Que nanoparticles (QNPs) were prepared with zein using an antisolvent method, and QNP-loaded calcium alginate hydrogel microspheres (QNP@HMs) were prepared using electrospinning technology to improve the gastrointestinal stability and intestinal adhesion of QNPs. In the mouse model of high-altitude sleep disturbance, oral administration of QNP@HMs before the mice entering high altitude prolonged sleep duration, improved blood cell recovery, spontaneous behavior and short-term memory, and reduced such inflammation factors as TNF-α and iNOS. Moreover, QNP@HMs enhanced the abundance of probiotics in the gut, including Lactobacillus and Lachnospira, and reduced intestinal inflammation. However, in the mice after gut sterilization by long-term oral antibiotics, QNP@HMs showed no therapeutic effect. QNP@HMs are a promising medication for the prevention of high-altitude sleep disturbance based on the gut-brain axis.


Subject(s)
Brain , Gastrointestinal Microbiome , Hydrogels , Microspheres , Nanoparticles , Quercetin , Animals , Quercetin/administration & dosage , Quercetin/pharmacology , Quercetin/chemistry , Nanoparticles/administration & dosage , Hydrogels/administration & dosage , Gastrointestinal Microbiome/drug effects , Administration, Oral , Male , Mice , Brain/drug effects , Brain/metabolism , Alginates/chemistry , Alginates/administration & dosage , Probiotics/administration & dosage
7.
PLoS One ; 19(5): e0304113, 2024.
Article in English | MEDLINE | ID: mdl-38820335

ABSTRACT

Microbial degradation of tylosin (TYL) is a safe and environmentally friendly technology for remediating environmental pollution. Kurthia gibsonii (TYL-A1) and Klebsiella pneumonia (TYL-B2) were isolated from wastewater; degradation efficiency of the two strains combined was significantly greater than either alone and resulted in degradation products that were less toxic than TYL. With Polyvinyl alcohol (PVA)-sodium alginate (SA)-activated carbon (AC) used to form a bacterial immobilization carrier, the immobilized bacterial alliance reached 95.9% degradation efficiency in 1 d and could be reused for four cycles, with > 93% degradation efficiency per cycle. In a wastewater application, the immobilized bacterial alliance degraded 67.0% TYL in 9 d. There were significant advantages for the immobilized bacterial alliance at pH 5 or 9, with 20 or 40 g/L NaCl, or with 10 or 50 mg/L doxycycline. In summary, in this study, a bacterial consortium with TYL degradation ability was constructed using PVA-SA-AC as an immobilized carrier, and the application effect was evaluated on farm wastewater with a view to providing application guidance in environmental remediation.


Subject(s)
Biodegradation, Environmental , Cells, Immobilized , Polyvinyl Alcohol , Tylosin , Wastewater , Wastewater/chemistry , Wastewater/microbiology , Polyvinyl Alcohol/chemistry , Cells, Immobilized/metabolism , Alginates/chemistry , Alginates/metabolism , Water Pollutants, Chemical/metabolism , Klebsiella pneumoniae/metabolism , Anti-Bacterial Agents , Charcoal/chemistry
8.
Int J Nanomedicine ; 19: 3861-3890, 2024.
Article in English | MEDLINE | ID: mdl-38708178

ABSTRACT

Introduction: Cystic fibrosis (CF) is associated with pulmonary Pseudomonas aeruginosa infections persistent to antibiotics. Methods: To eradicate pseudomonal biofilms, solid lipid nanoparticles (SLNs) loaded with quorum-sensing-inhibitor (QSI, disrupting bacterial crosstalk), coated with chitosan (CS, improving internalization) and immobilized with alginate lyase (AL, destroying alginate biofilms) were developed. Results: SLNs (140-205 nm) showed prolonged release of QSI with no sign of acute toxicity to A549 and Calu-3 cells. The CS coating improved uptake, whereas immobilized-AL ensured >1.5-fold higher uptake and doubled SLN diffusion across the artificial biofilm sputum model. Respirable microparticles comprising SLNs in carbohydrate matrix elicited aerodynamic diameters MMAD (3.54, 2.48 µm) and fine-particle-fraction FPF (65, 48%) for anionic and cationic SLNs, respectively. The antimicrobial and/or antibiofilm activity of SLNs was explored in Pseudomonas aeruginosa reference mucoid/nonmucoid strains as well as clinical isolates. The full growth inhibition of planktonic bacteria was dependent on SLN type, concentration, growth medium, and strain. OD measurements and live/dead staining proved that anionic SLNs efficiently ceased biofilm formation and eradicated established biofilms, whereas cationic SLNs unexpectedly promoted biofilm progression. AL immobilization increased biofilm vulnerability; instead, CS coating increased biofilm formation confirmed by 3D-time lapse confocal imaging. Incubation of SLNs with mature biofilms of P. aeruginosa isolates increased biofilm density by an average of 1.5-fold. CLSM further confirmed the binding and uptake of the labeled SLNs in P. aeruginosa biofilms. Considerable uptake of CS-coated SLNs in non-mucoid strains could be observed presumably due to interaction of chitosan with LPS glycolipids in the outer cell membrane of P. aeruginosa. Conclusion: The biofilm-destructive potential of QSI/SLNs/AL inhalation is promising for site-specific biofilm-targeted interventional CF therapy. Nevertheless, the intrinsic/extrinsic fundamentals of nanocarrier-biofilm interactions require further investigation.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chitosan , Liposomes , Nanoparticles , Pseudomonas Infections , Pseudomonas aeruginosa , Biofilms/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Humans , Pseudomonas Infections/drug therapy , Nanoparticles/chemistry , Chitosan/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Drug Carriers/chemistry , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Lipids/chemistry , Lipids/pharmacology , Quorum Sensing/drug effects , A549 Cells , Alginates/chemistry
9.
Carbohydr Polym ; 337: 122144, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710569

ABSTRACT

In vivo, cells interact with the extracellular matrix (ECM), which provides a multitude of biophysical and biochemical signals that modulate cellular behavior. Inspired by this, we explored a new methodology to develop a more physiomimetic polysaccharide-based matrix for 3D cell culture. Maleimide-modified alginate (AlgM) derivatives were successfully synthesized using DMTMM to activate carboxylic groups. Thiol-terminated cell-adhesion peptides were tethered to the hydrogel network to promote integrin binding. Rapid and efficient in situ hydrogel formation was promoted by thiol-Michael addition "click" chemistry via maleimide reaction with thiol-flanked protease-sensitive peptides. Alginate derivatives were further ionically crosslinked by divalent ions present in the medium, which led to greater stability and allowed longer cell culture periods. By tailoring alginate's biofunctionality we improved cell-cell and cell-matrix interactions, providing an ECM-like 3D microenvironment. We were able to systematically and independently vary biochemical and biophysical parameters to elicit specific cell responses, creating custom-made 3D matrices. DMTMM-mediated maleimide incorporation is a promising approach to synthesizing AlgM derivatives that can be leveraged to produce ECM-like matrices for a broad range of applications, from in vitro tissue modeling to tissue regeneration.


Subject(s)
Alginates , Click Chemistry , Extracellular Matrix , Hydrogels , Maleimides , Sulfhydryl Compounds , Maleimides/chemistry , Alginates/chemistry , Sulfhydryl Compounds/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Humans , Cross-Linking Reagents/chemistry , Cell Adhesion/drug effects , Animals
10.
Molecules ; 29(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38731511

ABSTRACT

Alginate films plasticized with glycerol and enriched in raspberry and/or black currant seed oils were prepared via casting solution techniques. The intention was to create active films for food packaging where antioxidants in a film would deactivate oxidants in a packed product or its surroundings, improving conditions inside packaging and extending the shelf life of such a product. The prepared materials were characterized by physicochemical, spectroscopic, mechanical, water vapor transmission (WVTR), and antioxidant activity analysis. Infrared spectra of the alginate films with oils were similar to those without the additive; the band with a maximum at about 1740 cm-1 stood out. The prepared materials with oils were thicker, contained less water, were more yellow, and were less permeable to water vapor. Moreover, the presence of the oil in the films resulted in a slightly lower Young's modulus and lower stress at break values but higher strain at break. The antioxidant capacity of raspberry seed oil itself was about five times higher than that of black currant seed oil, and a similar trend was noticed for films modified with these oils. The results indicated that both oils could be used as active substances with antioxidant properties in food packaging.


Subject(s)
Alginates , Antioxidants , Food Packaging , Plant Oils , Ribes , Rubus , Seeds , Food Packaging/methods , Alginates/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Plant Oils/chemistry , Seeds/chemistry , Rubus/chemistry , Ribes/chemistry , Steam
11.
Exp Dermatol ; 33(5): e15098, 2024 May.
Article in English | MEDLINE | ID: mdl-38770557

ABSTRACT

Healing of complex wounds requires dressings that must, at least, not hinder and should ideally promote the activity of key healing cells, in particular fibroblasts. This in vitro study assessed the effects of three wound-dressings (a pure Ca2+ alginate: Algostéril®, a Ca2+ alginate + carboxymethylcellulose: Biatain alginate® and a polyacrylate impregnated with lipido-colloid matrix: UrgoClean®) on dermal fibroblast activity. The results showed the pure calcium alginate to be non-cytotoxic, whereas the other wound-dressings showed moderate to strong cytotoxicity. The two alginates stimulated fibroblast migration and proliferation, whereas the polyacrylate altered migration and had no effect on proliferation. The pure Ca2+ alginate significantly increased the TGF-ß-induced fibroblast activation, which is essential to healing. This activation was confirmed by a significant increase in Vascular endothelial growth factor (VEGF) secretion and a higher collagen production. The other dressings reduced these fibroblast activities. The pure Ca2+ alginate was also able to counteract the inhibitory effect of NK cell supernatants on fibroblast migration. These in vitro results demonstrate that tested wound-dressings are not equivalent for fibroblast activation. Only Algostéril was found to promote all the fibroblast activities tested, which could contribute to its healing efficacy demonstrated in the clinic.


Subject(s)
Alginates , Cell Movement , Cell Proliferation , Fibroblasts , Vascular Endothelial Growth Factor A , Wound Healing , Fibroblasts/drug effects , Wound Healing/drug effects , Humans , Alginates/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Vascular Endothelial Growth Factor A/metabolism , Collagen/metabolism , Bandages , Transforming Growth Factor beta/metabolism , Carboxymethylcellulose Sodium , Cells, Cultured , Killer Cells, Natural/drug effects , Acrylic Resins , Hexuronic Acids , Glucuronic Acid , Skin
12.
ACS Nano ; 18(20): 12917-12932, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38720520

ABSTRACT

Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.


Subject(s)
Inflammatory Bowel Diseases , Nanoparticles , Polyphenols , Probiotics , Tannins , Animals , Probiotics/pharmacology , Probiotics/chemistry , Probiotics/administration & dosage , Polyphenols/chemistry , Polyphenols/pharmacology , Mice , Nanoparticles/chemistry , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/therapy , Tannins/chemistry , Tannins/pharmacology , Mice, Inbred C57BL , Escherichia coli/drug effects , Dextran Sulfate/chemistry , Alginates/chemistry , Alginates/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology
13.
Nanoscale ; 16(20): 10048-10063, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38712552

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition that encompasses a wide range of liver diseases that progresses from simple hepatic steatosis to the life-threatening state of cirrhosis. However, due to the heterogeneity of this disease, comprehensive analysis of several physicochemical and biological factors that drive its progression is necessary. Therefore, an in vitro platform is required that would enable real-time monitoring of these changes to better understand the progression of these diseases. The earliest stage of NAFLD, i.e. hepatic steatosis, is characterised by triglyceride accumulation in the form of lipid vacuoles in the cytosol of hepatocytes. This fatty acid accumulation is usually accompanied by hepatic inflammation, leading to tissue acidification and dysregulated expression of certain proteases such as matrix metalloproteinases (MMPs). Taking cues from the biological parameters of the disease, we report here a 3D in vitro GelMA/alginate microscaffold platform encapsulating a triple-marker (pH, MMP-3 and MMP-9) sensitive fluorescent nanoprobe for monitoring, and hence, distinguishing the fatty liver disease (hepatic steatosis) from healthy livers on the basis of pH change and MMP expression. The nanoprobe consists of a carbon nanoparticle (CNP) core, which exhibits intrinsic pH-dependent fluorescence properties, decorated either with an MMP-3 (NpMMP3) or MMP-9 (NpMMP9) sensitive peptide substrate. These peptide substrates are flanked with a fluorophore-quencher pair that separates on enzymatic cleavage, resulting in fluorescence emission. The cocktail of these nanoprobes generated multiple fluorescence signals corresponding to slightly acidic pH (blue) and overexpression of MMP-3 (green) and MMP-9 (red) enzymes in a 3D in vitro fatty liver model, whereas no/negligible fluorescence signals were observed in a healthy liver model. Moreover, this platform enabled us to mimic fatty liver disease in a more realistic manner. Therefore, this 3D in vitro platform encapsulating triple-marker sensitive fluorescent nanoprobes would facilitate the monitoring of the changes in pH and MMP expression, thereby enabling us to distinguish a healthy liver from a diseased liver and to study liver disease stages on the basis of these markers.


Subject(s)
Matrix Metalloproteinase 3 , Matrix Metalloproteinase 9 , Non-alcoholic Fatty Liver Disease , Matrix Metalloproteinase 9/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Humans , Hydrogen-Ion Concentration , Matrix Metalloproteinase 3/metabolism , Nanoparticles/chemistry , Fluorescent Dyes/chemistry , Alginates/chemistry , Hep G2 Cells , Tissue Scaffolds/chemistry , Hepatocytes/metabolism
14.
ACS Appl Mater Interfaces ; 16(20): 25652-25664, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38739871

ABSTRACT

Aqueous core-shell structures can serve as an efficient approach that allows cells to generate 3D spheroids with in vivo-like cell-to-cell contacts. Here, a novel strategy for fabricating liquid-core-shell capsules is proposed by inverse gelation of alginate (ALG) and layer-by-layer (LbL) coating. We hypothesized that the unique properties of polyethylenimine (PEI) could be utilized to overcome the low structural stability and the limited cell recognition motifs of ALG. In the next step, alginate dialdehyde (ADA) enabled the Schiff-base reaction with free amine groups of PEI to reduce its possible toxic effects. Scanning electron microscopy and light microscopy images proved the formation of spherical hollow capsules with outer diameters of 3.0 ± 0.1 mm for ALG, 3.2 ± 0.1 mm for ALG/PEI, and 4.0 ± 0.2 mm for ALG/PEI/ADA capsules. The effective modulus increased by 3-fold and 5-fold when comparing ALG/PEI/ADA and ALG/PEI to ALG capsules, respectively. Moreover, PEI-coated capsules showed potential antibacterial properties against both Staphylococcus aureus and Escherichia coli, with an apparent inhibition zone. The cell viability results showed that all capsules were cytocompatible (above 75.5%). Cells could proliferate and form spheroids when encapsulated within the ALG/PEI/ADA capsules. Monitoring the spheroid thickness over 5 days of incubation indicated an increasing trend from 39.50 µm after 1 day to 66.86 µm after 5 days. The proposed encapsulation protocol represents a new in vitro platform for developing 3D cell cultivation and can be adapted to fulfill the requirements of various biomedical applications.


Subject(s)
Alginates , Anti-Bacterial Agents , Capsules , Escherichia coli , Polyethyleneimine , Staphylococcus aureus , Alginates/chemistry , Polyethyleneimine/chemistry , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Capsules/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Cell Survival/drug effects , Animals
15.
Nano Lett ; 24(19): 5894-5903, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38709593

ABSTRACT

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.


Subject(s)
Chemokine CCL21 , Dendritic Cells , Hydrogels , Animals , Hydrogels/chemistry , Mice , Dendritic Cells/drug effects , Dendritic Cells/immunology , Cell Line, Tumor , Humans , Alginates/chemistry , Neoplasms/radiotherapy , Neoplasms/pathology , Neoplasms/immunology , Collagen/chemistry , Immunotherapy/methods
16.
J Nanobiotechnology ; 22(1): 241, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735933

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.


Subject(s)
Fatty Acids, Volatile , Gastrointestinal Microbiome , Limosilactobacillus reuteri , Probiotics , Gastrointestinal Microbiome/drug effects , Probiotics/pharmacology , Humans , Fatty Acids, Volatile/metabolism , Animals , Limosilactobacillus reuteri/metabolism , Mice , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Administration, Oral , Colorectal Neoplasms/drug therapy , Cell Line, Tumor , Receptors, G-Protein-Coupled/metabolism , Microgels/chemistry , Mice, Inbred BALB C , Butyric Acid/pharmacology , Butyric Acid/metabolism
17.
ACS Appl Mater Interfaces ; 16(19): 25317-25332, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38706308

ABSTRACT

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.


Subject(s)
Femur , Glass , Mandible , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Glass/chemistry , Mandible/diagnostic imaging , Mandible/surgery , Mandible/drug effects , Femur/drug effects , Femur/diagnostic imaging , Femur/pathology , Gelatin/chemistry , Bone Regeneration/drug effects , Alginates/chemistry , Porosity , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering
18.
Sci Rep ; 14(1): 10931, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740842

ABSTRACT

Biomaterial scaffolds play a pivotal role in the advancement of cultured meat technology, facilitating essential processes like cell attachment, growth, specialization, and alignment. Currently, there exists limited knowledge concerning the creation of consumable scaffolds tailored for cultured meat applications. This investigation aimed to produce edible scaffolds featuring both smooth and patterned surfaces, utilizing biomaterials such as salmon gelatin, alginate, agarose and glycerol, pertinent to cultured meat and adhering to food safety protocols. The primary objective of this research was to uncover variations in transcriptomes profiles between flat and microstructured edible scaffolds fabricated from marine-derived biopolymers, leveraging high-throughput sequencing techniques. Expression analysis revealed noteworthy disparities in transcriptome profiles when comparing the flat and microstructured scaffold configurations against a control condition. Employing gene functional enrichment analysis for the microstructured versus flat scaffold conditions yielded substantial enrichment ratios, highlighting pertinent gene modules linked to the development of skeletal muscle. Notable functional aspects included filament sliding, muscle contraction, and the organization of sarcomeres. By shedding light on these intricate processes, this study offers insights into the fundamental mechanisms underpinning the generation of muscle-specific cultured meat.


Subject(s)
Cell Differentiation , Meat , Tissue Scaffolds , Transcriptome , Tissue Scaffolds/chemistry , Animals , Biopolymers , Muscle Development/genetics , Alginates/chemistry , Gene Expression Profiling , Sepharose/chemistry , Biocompatible Materials/chemistry , Gelatin/chemistry , Muscle Cells/metabolism , Salmon , In Vitro Meat
19.
Sci Rep ; 14(1): 9972, 2024 04 30.
Article in English | MEDLINE | ID: mdl-38693342

ABSTRACT

This study presents a novel biosorbent developed by immobilizing dead Sp2b bacterial biomass into calcium alginate (CASp2b) to efficiently remove arsenic (AsIII) from contaminated water. The bacterium Sp2b was isolated from arsenic-contaminated industrial soil of Punjab, a state in India. The strain was designated Acinetobacter sp. strain Sp2b as per the 16S rDNA sequencing, GenBank accession number -OP010048.The CASp2b was used for the biosorption studies after an initial screening for the biosorption capacity of Sp2b biomass with immobilized biomass in both live and dead states. The optimum biosorption conditions were examined in batch experimentations with contact time, pH, biomass, temperature, and AsIII concentration variables. The maximum biosorption capacity (qmax = 20.1 ± 0.76 mg/g of CA Sp2b) was obtained at pH9, 35 ̊ C, 20 min contact time, and 120 rpm agitation speed. The isotherm, kinetic and thermodynamic modeling of the experimental data favored Freundlich isotherm (R2 = 0.941) and pseudo-2nd-order kinetics (R2 = 0.968) with endothermic nature (ΔH° = 27.42) and high randomness (ΔS° = 58.1).The scanning electron microscopy with energy dispersive X-ray (SEM-EDX) analysis indicated the As surface binding. The reusability study revealed the reasonable usage of beads up to 5 cycles. In conclusion, CASp2b is a promising, efficient, eco-friendly biosorbent for AsIII removal from contaminated water.


Subject(s)
Acinetobacter , Alginates , Arsenic , Biodegradation, Environmental , Biomass , Water Pollutants, Chemical , Alginates/chemistry , Alginates/metabolism , Acinetobacter/metabolism , Acinetobacter/genetics , Arsenic/metabolism , Water Pollutants, Chemical/metabolism , Adsorption , Kinetics , Hydrogen-Ion Concentration , Water Purification/methods , Temperature , Thermodynamics
20.
J Mech Behav Biomed Mater ; 155: 106579, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749266

ABSTRACT

Silicon nitride is utilized clinically as a bioceramic for spinal fusion cages, owing to its high strength, osteoconductivity, and antibacterial effects. Nevertheless, silicon nitride exhibits suboptimal damping properties, a critical factor in mitigating traumatic bone injuries and fractures. In fact, there is a scarcity of spinal implants that simultaneously demonstrate proficient damping performance and support osteogenesis. In our study, we fabricated a novel sodium alginate-silicon nitride/poly(vinyl alcohol) (SA-SiN/PVA) composite scaffold, enabling enhanced energy absorption and rapid elastic recovery under quasi-static and impact loading scenarios. Furthermore, the study demonstrated that the incorporation of physical and chemical cross-linking significantly improved stiffness and recoverable energy dissipation. Concerning the interaction between cells and materials, our findings suggest that the addition of silicon nitride stimulated osteogenic differentiation while inhibiting Staphylococcus aureus growth. Collectively, the amalgamation of ceramics and tough hydrogels facilitates the development of advanced composites for spinal implants, manifesting superior damping, osteogenic potential, and antibacterial properties. This approach holds broader implications for applications in bone tissue engineering.


Subject(s)
Alginates , Biocompatible Materials , Materials Testing , Polyvinyl Alcohol , Silicon Compounds , Staphylococcus aureus , Alginates/chemistry , Alginates/pharmacology , Polyvinyl Alcohol/chemistry , Silicon Compounds/chemistry , Silicon Compounds/pharmacology , Staphylococcus aureus/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Osteogenesis/drug effects , Mechanical Phenomena , Tissue Scaffolds/chemistry , Humans
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