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1.
Breast Cancer Res ; 26(1): 63, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38605414

BACKGROUND: Chitinase-like proteins (CLPs) play a key role in immunosuppression under inflammatory conditions such as cancer. CLPs are enzymatically inactive and become neutralized upon binding of their natural ligand chitin, potentially reducing CLP-driven immunosuppression. We investigated the efficacy of chitin treatment in the context of triple-negative breast cancer (TNBC) using complementary mouse models. We also evaluated the immunomodulatory influence of chitin on immune checkpoint blockade (ICB) and compared its efficacy as general CLP blocker with blockade of a single CLP, i.e. chitinase 3-like 1 (CHI3L1). METHODS: Female BALB/c mice were intraductally injected with luciferase-expressing 4T1 or 66cl4 cells and systemically treated with chitin in combination with or without anti-programmed death (PD)-1 ICB. For single CLP blockade, tumor-bearing mice were treated with anti-CHI3L1 antibodies. Metastatic progression was monitored through bioluminescence imaging. Immune cell changes in primary tumors and lymphoid organs (i.e. axillary lymph nodes and spleen) were investigated through flow cytometry, immunohistochemistry, cytokine profiling and RNA-sequencing. CHI3L1-stimulated RAW264.7 macrophages were subjected to 2D lymphatic endothelial cell adhesion and 3D lymphatic integration in vitro assays for studying macrophage-mediated lymphatic remodeling. RESULTS: Chitin significantly reduced primary tumor progression in the 4T1-based model by decreasing the high production of CLPs that originate from tumor-associated neutrophils (TANs) and Stat3 signaling, prominently affecting the CHI3L1 and CHI3L3 primary tumor levels. It reduced immunosuppressive cell types and increased anti-tumorigenic T-cells in primary tumors as well as axillary lymph nodes. Chitin also significantly reduced CHI3L3 primary tumor levels and immunosuppression in the 66cl4-based model. Compared to anti-CHI3L1, chitin enhanced primary tumor growth reduction and anti-tumorigenicity. Both treatments equally inhibited lymphatic adhesion and integration of macrophages, thereby hampering lymphatic tumor cell spreading. Upon ICB combination therapy, chitin alleviated anti-PD-1 resistance in both TNBC models, providing a significant add-on reduction in primary tumor and lung metastatic growth compared to chitin monotherapy. These add-on effects occurred through additional increase in CD8α+ T-cell infiltration and activation in primary tumor and lymphoid organs. CONCLUSIONS: Chitin, as a general CLP blocker, reduces CLP production, enhances anti-tumor immunity as well as ICB responses, supporting its potential clinical relevance in immunosuppressed TNBC patients.


Chitin , Chitinases , Triple Negative Breast Neoplasms , Animals , Female , Humans , Mice , Cell Line, Tumor , Chitin/pharmacology , Chitin/therapeutic use , Chitinases/therapeutic use , Immunosuppression Therapy , Lymphatic Metastasis , Proteins/therapeutic use , Triple Negative Breast Neoplasms/pathology
2.
Int J Biol Macromol ; 265(Pt 2): 131120, 2024 Apr.
Article En | MEDLINE | ID: mdl-38527680

Chitin is the second most abundant biopolymer and its inherent biological characteristics make it ideal to use for tissue engineering. For many decades, its properties like non-toxicity, abundant availability, ease of modification, biodegradability, biocompatibility, and anti-microbial activity have made chitin an ideal biopolymer for drug delivery. Research studies have also shown many potential benefits of chitin in the formulation of functional therapy for cartilage regeneration. Chitin and its derivatives can be processed into 2D/3D scaffolds, hydrogels, films, exosomes, and nano-fibers, which make it a versatile and functional biopolymer in tissue engineering. Chitin is a biomimetic polymer that provides targeted delivery of mesenchymal stem cells, especially of chondrocytes at the injected donor sites to accelerate regeneration by enhancing cell proliferation and differentiation. Due to this property, chitin is considered an interesting polymer that has a high potential to provide targeted therapy in the regeneration of cartilage. Our paper presents an overview of the method of extraction, structure, properties, and functional role of this versatile biopolymer in tissue engineering, especially cartilage regeneration.


Cartilage, Articular , Tissue Scaffolds , Tissue Scaffolds/chemistry , Chitin/pharmacology , Chitin/therapeutic use , Cartilage , Tissue Engineering/methods , Hydrogels/chemistry , Polymers
3.
Carbohydr Res ; 536: 109042, 2024 Feb.
Article En | MEDLINE | ID: mdl-38244321

Two selenized chitooligosaccharide (O-Se-COS and N,O-Se-COS) with different sites modification were synthesized to alleviate liver injury in vivo. Comparing to traditional COS, both selenized COS exhibited enhanced reducibility as well as antioxidant capacity in vitro. Furthermore, O-Se-COS demonstrated superior efficacy in reducing intracellular reactive oxygen species (ROS) and mitochondrial damage compared to N,O-Se-COS as its enhanced cellular uptake by the positive/negative charge interactions. Two mechanisms were proposed to explained these results: one is to enhance the enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which effectively scavenge free radicals; the other is to down-regulate intracellular cytochrome P450 (CYP2E1) levels, inhibiting carbon tetrachloride (CCl4)-induced peroxidation damage. In vivo studies further demonstrated the effective alleviation of CCl4-induced liver injury by selenized COS, with therapeutic efficacy observed in the following order: O-Se-COS > N,O-Se-COS > COS. Finally, hemolysis and histological tests confirmed the biosafety of both selenized COS. Taken together, these finding demonstrated that selenium has the potential to improve the biological activity of COS, and precise selenylation was more conducive to achieving the synergistic effect where 1 + 1>2.


Chitosan , Liver , Oligosaccharides , Selenium , Antioxidants/pharmacology , Carbon Tetrachloride/toxicity , Carbon Tetrachloride/metabolism , Reactive Oxygen Species/metabolism , Chitin/pharmacology , Chitin/therapeutic use , Chitin/metabolism , Oxidative Stress , Selenium/pharmacology , Selenium/metabolism
4.
Biomater Adv ; 155: 213682, 2023 Dec.
Article En | MEDLINE | ID: mdl-37925826

Chronic wounds are a worldwide problem that affect >40 million people every year. The constant inflammatory status accompanied by prolonged bacterial infections reduce patient's quality of life and life expectancy drastically. An important cell type involved in the wound healing process are mesenchymal stromal cells (MSCs) due to their long-term demonstrated immunomodulatory and pro-regenerative capacity. Thus, in this work, we leveraged and compared the therapeutic properties of MSCs derived from both adipose tissue and hair follicle, which we combined with sponge-like scaffolds (SLS) made of valorized soy protein and ß-chitin. In this regard, the combination of these cells with biomaterials permitted us to obtain a multifunctional therapy that allowed high cell retention and growing rates while maintaining adequate cell-viability for several days. Furthermore, this combined therapy demonstrated to increase fibroblasts and keratinocytes migration, promote human umbilical vein endothelial cells angiogenesis and protect fibroblasts from highly proteolytic environments. Finally, this combined therapy demonstrated to be highly effective in reducing wound healing time in vivo with only one treatment change during all the experimental procedure, also promoting a more functional and native-like healed skin.


Diabetes Mellitus , Mesenchymal Stem Cells , Humans , Soybean Proteins/pharmacology , Soybean Proteins/therapeutic use , Soybean Proteins/metabolism , Hair Follicle , Chitin/pharmacology , Chitin/therapeutic use , Chitin/metabolism , Quality of Life , Wound Healing , Mesenchymal Stem Cells/metabolism , Adipose Tissue , Diabetes Mellitus/metabolism , Human Umbilical Vein Endothelial Cells
5.
Biomater Sci ; 11(17): 5908-5917, 2023 Aug 22.
Article En | MEDLINE | ID: mdl-37458611

Timely control of coagulopathy bleeding can effectively reduce the probability of wound infection and mortality. However, it is still a challenge for microsphere hemostatic agents to achieve timely control of coagulopathy bleeding. In this work, the CCM-g-AA@DA hemostatic agent based on carboxymethyl chitin microspheres, CCM, was synthesized using electron beam irradiation-induced grafting polymerization of acrylic acid and coupling with dopamine. Irradiation grafting endowed the microspheres with excellent adsorption performance and a rough surface. The microspheres showed a strong affinity to blood cells, especially red blood cells. The maximum adsorption of red blood cells is up to approximately 100 times that of the original microspheres, the CCM. The introduction of dopamine increased the tissue adhesion of the microspheres. At the same time, the microspheres still possessed good blood compatibility and biodegradability. Furthermore, the CCM-g-AA@DA with Fe3+ achieved powerful procoagulant effects in the rat anticoagulant bleeding model. The bleeding time and blood loss were both reduced by about 90% compared with the blank group, which was superior to that of the commercially available collagen hemostatic agent Avitene™. In summary, the CCM-g-AA@DA hemostatic agent shows promising potential for bleeding control in individuals with coagulation disorders.


Hemostatics , Rats , Animals , Hemostatics/therapeutic use , Hemostatics/pharmacology , Microspheres , Adsorption , Dopamine , Electrons , Hemorrhage/drug therapy , Chitin/therapeutic use , Erythrocytes
6.
J Clin Neurosci ; 114: 70-76, 2023 Aug.
Article En | MEDLINE | ID: mdl-37321020

OBJECTIVE: Rapid and efficacious haemostasis is paramount in neurosurgery. Assessing the efficacy and short- and long-term safety of haemostatic agents utilised within cerebral tissue is essential. This pilot study investigates the haemostatic efficacy and long-term safety of a novel beta-chitin patch against traditionally used agents, bipolar and Floseal, within cerebral tissue. METHODS: Eighteen Merino sheep underwent standardised distal cortical vessel injury via temporal craniotomy. Sheep were randomised to receive 2 mls Floseal, 2 cm novel beta-chitin patch, or bipolar cautery to manage bleeding. All sheep underwent cerebral magnetic resonance imaging (MRI) at three months, before euthanasia and brain harvesting for histological assessment. RESULTS: Beta-chitin demonstrated a trend towards a faster mean time to haemostasis (TTH) compared to Floseal (223.3 ± 199 s v. 259.8 ± 186.4 s), albeit non-significant (p = 0.234). Radiologically, cerebrocortical necrosis (p = 0.842) and oedema (p = 0.368) were noted slightly more frequently in the beta-chitin group. Histologically, severe fibrotic (p = 0.017) and granulomatous changes at the craniotomy sites were only present in the beta-chitin group (p = 0.002). Neuronal degeneration was seen in all with Floseal, but beta-chitin showed a trend towards more severe reaction when present. Bipolar use predominantly showed an inflammatory cortical reaction with substantial microvascular proliferation, and Floseal showed worse severity and depth of subpial oedema, however no statistical significance was reached. CONCLUSION: All haemostats controlled bleeding, with beta-chitin demonstrating a non-inferior TTH compared to Floseal. However, it resulted in intense granulomatous and fibrotic changes, including degenerative neuronal reactions. More extensive studies are needed to assess these trends, to make further clinical inferences.


Hemostatics , Sheep , Animals , Hemostatics/pharmacology , Pilot Projects , Gelatin Sponge, Absorbable , Hemostasis , Hemostasis, Surgical/methods , Chitin/pharmacology , Chitin/therapeutic use
7.
Carbohydr Polym ; 313: 120888, 2023 Aug 01.
Article En | MEDLINE | ID: mdl-37182974

Barrier membranes with osteogenesis are desirable for promoting bone repair. Janus membrane, which has a bilayered structure with different properties on each side, could meet the osteogenesis/barrier dual functions of guided bone regeneration. In this work, new biodegradable Janus carboxymethyl chitin membrane with asymmetric pore structure was prepared based on thermosensitive carboxymethyl chitin without using any crosslinkers. Nano-hydroxyapatites were cast on single-sided membrane. The obtained carboxymethyl chitin/nano-hydroxyapatite Janus membrane showed dual biofunctions: the dense layer of the Janus membrane could act as a barrier to prevent connective tissue cells from invading the bone defects, while the porous layer (with pore size 100-200 µm) containing nano-hydroxyapatite could guide bone regeneration. After implanted on the rat critical-sized calvarial defect 8 weeks, carboxymethyl chitin/nano-hydroxyapatite membrane showed the most newly formed bone tissue with the highest bone volume/total volume ratio (10.03 ± 1.81 %, analyzed by micro CT), which was significantly better than the commercial collagen membrane GTR® (5.05 ± 0.76 %). Meanwhile, this Janus membrane possessed good hemostatic ability. These results suggest a facile strategy to construct hemostasis-osteogenesis integrated Janus carboxymethyl chitin/hydroxyapatite membrane for guided bone regeneration.


Durapatite , Osteogenesis , Rats , Animals , Durapatite/pharmacology , Durapatite/chemistry , Porosity , Chitin/pharmacology , Chitin/therapeutic use , Chitin/chemistry , Bone Regeneration , Hemostasis
8.
Carbohydr Polym ; 306: 120575, 2023 Apr 15.
Article En | MEDLINE | ID: mdl-36746566

Infections caused by bacteria have long constituted a major threat to human health and the economy. Therefore, there is an urgent need to design broad-spectrum antibacterial materials possessing good biocompatibility to treat such infections. Herein, inspired by the good biocompatibility of chitin and antibacterial properties of imidazolium salts, a polysaccharide-based material, imidazolium salt chitin (IMSC), was homogeneously prepared using a facile method with epichlorohydrin as a chemical crosslinker to combine chitin with imidazole to enhance Staphylococcus aureus (S. aureus)-infected wound healing. The characteristics, antimicrobial properties, and biosafety of IMSC were evaluated. The results demonstrated successful grafting of imidazole onto chitin. Furthermore, IMSC exhibited good water solubility, broad-spectrum antimicrobial activity, hemocompatibility, and biocompatibility. Moreover, IMSC enabled complete healing of S. aureus-infected wound in Sprague-Dawley rats within 15 days of application, thus demonstrating that IMSC could reduce wound inflammation and remarkably accelerate wound healing owing to its efficient antibacterial activity and ability to promote collagen deposition in and around the wound area. Therefore, this study provides a promising and potential therapeutic strategy for infected wound healing by synthesizing a water-soluble and broad-spectrum antimicrobial material exhibiting good biocompatibility.


Anti-Infective Agents , Wound Infection , Rats , Animals , Humans , Staphylococcus aureus , Rats, Sprague-Dawley , Escherichia coli , Wound Healing , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/chemistry , Chitin/pharmacology , Chitin/therapeutic use , Chitin/chemistry , Sodium Chloride , Water/chemistry , Wound Infection/drug therapy
9.
Carbohydr Polym ; 305: 120543, 2023 Apr 01.
Article En | MEDLINE | ID: mdl-36737194

Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.


Chitin , Hydrogels , Rats , Animals , Chitin/pharmacology , Chitin/therapeutic use , Hydrogels/pharmacology , Quality of Life , Peritoneum/pathology , Biocompatible Materials/pharmacology , Biocompatible Materials/therapeutic use , Tissue Adhesions/prevention & control
10.
Biomater Sci ; 10(20): 6024-6036, 2022 Oct 11.
Article En | MEDLINE | ID: mdl-36073016

Non-functional scars commonly form after cutaneous injuries. At present, most clinical treatments for scar eradication typically have long treatment courses, low curative effects, and are expensive. In this research, three hydrogels, namely chitin hydrogel, ß-glucan hydrogel, and hybrid hydrogel composed of chitin and ß-glucan, were successfully prepared, and they exhibited good shear thinning property and bioadhesiveness. In a full-thickness skin defect mouse model, the three hydrogels were found to effectively promote wound closure and inhibit scar formation. Through the immunohistochemistry staining and immunofluorescence staining of the wound tissues, the hydrogels could significantly promote the formation of collagen III, the regeneration of hair follicles, and the expression of keratin K14 and K15. They could also regulate the production of VEGF and immune factors such as IL-10 and IL-12, and inhibit the expression of the fibroblast regulatory factor En-1 in the wound site, which correlated well with their improved wound healing promoting effect and anti-scarring effect. Among all the hydrogels, the hybrid hydrogel was the best to promote wound healing and inhibit scarring. This study, for the first time, proved the excellent therapeutic effect of chitin and ß-glucan hydrogels in the management of wound healing and skin regeneration without scar formation, which will lay a solid foundation for the development of skin regeneration medication and future clinical transformation.


Hydrogels , beta-Glucans , Animals , Chitin/pharmacology , Chitin/therapeutic use , Cicatrix/drug therapy , Collagen/pharmacology , Hydrogels/chemistry , Interleukin-10/pharmacology , Interleukin-12 , Keratins , Mice , Vascular Endothelial Growth Factor A/pharmacology , Wound Healing , beta-Glucans/pharmacology , beta-Glucans/therapeutic use
11.
Carbohydr Polym ; 291: 119553, 2022 Sep 01.
Article En | MEDLINE | ID: mdl-35698381

Efficient hemostasis is a great challenge for treating the inaccessible hemorrhage wounds. A novel shape-memory chitin-glucan hemostatic sponge (ATC-Sponge) is constructed via sequentially in-situ removal of protein and glucan from Pleurotus eryngii fruiting body, TEMPO oxidation and Ca2+ crosslinking. The sponge displays interconnected microporous structure with high water absorption and robust mechanical properties. The sponge at dry state shows rapid blood-triggered shape-memory, allowing easy insertion into the puncture wound in a compressed fixed-shape and the subsequent quick volume expansion to conform wound shape to stop bleeding. Compared with standard medical gauze and gelatin sponge, ATC-Sponge demonstrates superior hemostatic performance in the rat femoral artery and non-compressive liver puncture injury models. Additionally, ATC-Sponge can effectively accelerate wound healing. This multi-functional shape-memory ATC-Sponge shows high potential in controlling the bleeding of inaccessible traumas.


Chitin , Hemostatics , Animals , Chitin/pharmacology , Chitin/therapeutic use , Glucans , Hemorrhage/drug therapy , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostatics/therapeutic use , Pleurotus , Punctures , Rats
12.
Carbohydr Polym ; 269: 118276, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34294308

The guided tissue regeneration technique is an effective approach to repair periodontal defect. However, collagen barrier membranes used clinically lose stability easily, leading to soft tissue invasion, surgical site infection, and failure of osteogenesis. An ideal barrier membrane should possess proper antibacterial, osteoconductive activities, and favorable biodegradation. In this study, zinc oxide nanoparticles were homogeneously incorporated into the chitin hydrogel (ChT-1%ZnO) through one-step dissolution and regeneration method from alkaline/urea solution the first time. The remaining weights of ChT-1%ZnO in 150 µg/mL lysozyme solution was 52% after 5 weeks soaking. ChT-1%ZnO showed statistical antibacterial activities for P. gingivalis and S. aureus at 6 h, 12 h, and 24 h. Moreover, ChT-1%ZnO exhibits osteogenesis promotion in vitro, and it was further evaluated with rat periodontal defect model in vivo. The cemento-enamel junction value in ChT-1%ZnO group is 1.608 mm, presenting a statistical difference compared with no-membrane (1.825 mm) and ChT group (1.685 mm) after 8 weeks postoperatively.


Anti-Bacterial Agents/therapeutic use , Chitin/therapeutic use , Hydrogels/therapeutic use , Membranes, Artificial , Osteogenesis/drug effects , Periodontal Diseases/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Cell Proliferation/drug effects , Chitin/chemistry , Chitin/toxicity , Female , Guided Tissue Regeneration/methods , Hydrogels/chemistry , Hydrogels/toxicity , Microbial Sensitivity Tests , Periodontal Diseases/pathology , Porphyromonas gingivalis/drug effects , Rats, Wistar , Staphylococcus aureus/drug effects , Tooth/drug effects , Tooth/pathology , Zinc Oxide/chemistry , Zinc Oxide/therapeutic use , Zinc Oxide/toxicity
13.
BMC Microbiol ; 21(1): 190, 2021 06 25.
Article En | MEDLINE | ID: mdl-34171998

BACKGROUND: Fungal cell wall polysaccharides maintain the integrity of fungi and interact with host immune cells. The immunomodulation of fungal polysaccharides has been demonstrated in previous studies. However, the effect of chitin-rich heteroglycan extracted from Sporothrix schenckii sensu stricto on the immune response has not been investigated. RESULTS: In this study, chitin-rich heteroglycan was extracted from S. schenckii sensu stricto, and immunomodulation was investigated via histopathological analysis of skin lesions in a mouse model of sporotrichosis and evaluation of the phagocytic function and cytokine secretion of macrophages in vitro. The results showed that the skin lesions regressed and granulomatous inflammation was reduced in infected mice within 5 weeks. Moreover, heteroglycan promoted the fungal phagocytosis by macrophages and modulated the cytokine secretion. Heteroglycan upregulated TNF-α expression early at 24 h and IL-12 expression late at 72 h after incubation, which might result from moderate activation of macrophages and contribute to the subsequent adaptive immune response. CONCLUSIONS: Chitin-rich heteroglycan extracted from S. schenckii sensu stricto potentiated fungal clearance in a mouse model of sporotrichosis. Moreover, chitin-rich heteroglycan promoted fungus phagocytosis by macrophages and modulated cytokines secretion. These results might indicate that chitin-rich heteroglycan could be considered as an immunomodulator used in the treatment of sporotrichosis.


Macrophages/drug effects , Phagocytosis/drug effects , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Sporothrix/chemistry , Sporotrichosis/drug therapy , Animals , Chitin/chemistry , Chitin/pharmacology , Chitin/therapeutic use , Fungi/drug effects , Gene Expression Regulation/drug effects , Immunomodulating Agents/chemistry , Immunomodulating Agents/isolation & purification , Immunomodulating Agents/pharmacology , Immunomodulating Agents/therapeutic use , Mice , Polysaccharides/chemistry , Polysaccharides/isolation & purification
14.
Carbohydr Polym ; 266: 118100, 2021 Aug 15.
Article En | MEDLINE | ID: mdl-34044919

Moist, breathable and antibacterial microenvironment can promote cell proliferation and migration, which is beneficial to wound healing. Here, we fabricated a novel sodium alginate-chitosan oligosaccharide­zinc oxide (SA-COS-ZnO) composite hydrogel by spontaneous Schiff base reaction, using aldehydated sodium alginate (SA), chitosan oligosaccharide (COS), and zinc oxide (ZnO) nanoparticles, which can provide a moist and antibacterial environment for wound healing. The porosity and swelling degree of SA-COS-ZnO hydrogel are 80% and 150%, respectively, and its water vapor permeability is 682 g/m2/24h. The composite hydrogel showed good biocompatibility to blood cells, 3T3 cells, and 293T cells, and significant antibacterial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and Bacillus subtilis. Moreover, the hydrogel showed a promoting effect on wound healing in a rat scald model. The present study suggests that marine carbohydrates composite hydrogels are promising in wound care management.


Anti-Infective Agents/therapeutic use , Hydrogels/therapeutic use , Polysaccharides/therapeutic use , Wound Healing/drug effects , Zinc Oxide/therapeutic use , Alginates/chemistry , Alginates/therapeutic use , Alginates/toxicity , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/toxicity , Bacillus subtilis/drug effects , Candida albicans/drug effects , Cell Line , Chitin/analogs & derivatives , Chitin/chemistry , Chitin/therapeutic use , Chitin/toxicity , Chitosan , Escherichia coli/drug effects , Hemolysis/drug effects , Humans , Hydrogels/chemistry , Hydrogels/toxicity , Male , Mice , Microbial Sensitivity Tests , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Oligosaccharides , Polysaccharides/chemistry , Polysaccharides/toxicity , Porosity , Rats, Sprague-Dawley , Staphylococcus aureus/drug effects , Zinc Oxide/chemistry , Zinc Oxide/toxicity
15.
Carbohydr Polym ; 266: 118132, 2021 Aug 15.
Article En | MEDLINE | ID: mdl-34044948

Chitooligosaccharides (COS) are the degraded products of chitin or chitosan. COS is water-soluble, non-cytotoxic to organisms, readily absorbed through the intestine, and eliminated primarily through the kidneys. COS possess a wide range of biological activities, including immunomodulation, cholesterol-lowering, and antitumor activity. Although work on COS goes back at least forty years, several aspects remain unclear. This review narrates the recent developments in COS antitumor activities, while paying considerable attention to the impacts of physicochemical properties (such as molecular weight and degrees of deacetylation) and chemical modifications both in vitro and in vivo. COS derivatives not only improve some physicochemical properties, but also expand the range of applications in drug and gene delivery. COS (itself or as a drug carrier) can inhibit tumor cell proliferation and metastasis, which might be attributed to its ability to stimulate the immune response along with its anti-angiogenic activity. Further, an attempt has been made to report limitations and future research. The potential health benefits of COS and its derivatives against cancer may offer a new insight on their applications in food and medical fields.


Antineoplastic Agents/therapeutic use , Chitin/analogs & derivatives , Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Cell Proliferation/drug effects , Chitin/pharmacokinetics , Chitin/therapeutic use , Chitosan , Humans , Neoplasm Metastasis/drug therapy , Oligosaccharides
16.
Int J Biol Macromol ; 183: 235-244, 2021 Jul 31.
Article En | MEDLINE | ID: mdl-33930442

The progressive and fatal outbreak of the newly emerged coronavirus, SARS-CoV-2, necessitates rigorous collaboration of all health care systems and researchers from all around the world to bring such a devastating pandemic under control. As there is so far no officially approved drug or ideal vaccine for this disease, investigations on this infectious disease are actively pursued. Chitin and chitosan have shown promising results against viral infections. In this review, we first delve into the problematic consequences of viral pandemics followed by an introduction on SARS-CoV-2 taxonomical classification. Then, we elaborate on the immunology of COVID-19. Common antiviral therapies and their related limitations are described and finally, the potential applicability of chitin and chitosan to fight this overwhelming viral pandemic is addressed.


Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Chitin/therapeutic use , Chitosan/therapeutic use , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , Humans
17.
Acta Pharmacol Sin ; 42(6): 942-953, 2021 Jun.
Article En | MEDLINE | ID: mdl-33495520

Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg-1·d-1, po) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1ß, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP.


Chitosan/therapeutic use , Homeostasis/drug effects , Intestines/drug effects , Oligosaccharides/therapeutic use , Oxidative Stress/drug effects , Pancreatitis/drug therapy , Acute Disease , Animals , Apoptosis/drug effects , Chitin/analogs & derivatives , Chitin/therapeutic use , Gastrointestinal Microbiome/drug effects , Male , Mice, Inbred C57BL , Pancreas/drug effects , Pancreas/pathology , Pancreatitis/pathology , Signal Transduction/drug effects
18.
Molecules ; 25(24)2020 Dec 16.
Article En | MEDLINE | ID: mdl-33339290

Chitin is a long-chain polymer of N-acetyl-glucosamine, which is regularly found in the exoskeleton of arthropods including insects, shellfish and the cell wall of fungi. It has been known that chitin can be used for biological and biomedical applications, especially as a biomaterial for tissue repairing, encapsulating drug for drug delivery. However, chitin has been postulated as an inducer of proinflammatory cytokines and certain diseases including asthma. Likewise, chitosan, a long-chain polymer of N-acetyl-glucosamine and d-glucosamine derived from chitin deacetylation, and chitosan oligosaccharide, a short chain polymer, have been known for their potential therapeutic effects, including anti-inflammatory, antioxidant, antidiarrheal, and anti-Alzheimer effects. This review summarizes potential utilization and limitation of chitin, chitosan and chitosan oligosaccharide in a variety of diseases. Furthermore, future direction of research and development of chitin, chitosan, and chitosan oligosaccharide for biomedical applications is discussed.


Biocompatible Materials/chemistry , Chitin/analogs & derivatives , Chitosan/analogs & derivatives , Animals , Arthropods/metabolism , Biocompatible Materials/pharmacology , Biocompatible Materials/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/pathology , Chitin/pharmacology , Chitin/therapeutic use , Chitosan/pharmacology , Chitosan/therapeutic use , Drug Carriers/chemistry , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Nervous System Diseases/drug therapy , Nervous System Diseases/pathology
19.
Acta Sci Pol Technol Aliment ; 19(3): 279-289, 2020.
Article En | MEDLINE | ID: mdl-32978911

BACKGROUND: Recent shifts in lifestyles and diets have caused the incidence of obesity to increase rapidly, resulting in a serious threat to modern human health. There is a growing interest the use of plant or fungi derived supplements as a safe and effective means to treat obesity. In recent times, edible-medicinal fungi have garnered attention as therapeutics owing to their biocompatibility and effectiveness. Attempts to determine the therapeutic effects of these fungi have become a prime focus in drug discovery programs. Therefore, this study aimed to determine the anti-obesity effects of P. eryngii chitin in rats with obesity induced by administration of a high fat diet. METHODS: To investigate the therapeutic effects of chitin from Pleurotus eryngii on high fat diet-induce obesity, we treated obese rats with different concentrations of chitin from P. eryngii for 4 weeks, using Lipitor as positive control. The living condition, food intake, body weight, perirenal adipose tissue, periepididymal adipose tissue, adipose tissue coefficient, serum lipid levels, including total cholesterol (TC), total glyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), were measured, and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), themalonaldehyde (MDA), and superoxide dismutase (SOD) activity in liver were determined. The rats were also monitored for pathological changes in the liver and aorta. RESULTS: These studies indicated that administration of chitin from P. eryngii could significantly decrease obese rat food utilization rates and accumulation of adipose tissue in the body, thus preventing development of increased body weight. The treatment also significantly reduced serum lipid levels, including levels of TC, TG and LDL-C. Treatment with P. eryngii-derived chitin also enhanced ALT and AST enzymatic activity, enhanced SOD enzymatic activity, and reduced the MDA content of the liver, as well as significantly reducing the liver index and alleviating liver steatosis and aortic atherosclerosis resulting from obesity. CONCLUSIONS: In conclusion, chitin from P. eryngii had therapeutic effects on hyperlipidemia, fatty liver, and aortic atherosclerosis resulting from obesity in rats.


Biological Products/therapeutic use , Body Weight/drug effects , Chitin/therapeutic use , Diet, High-Fat , Lipid Metabolism/drug effects , Obesity/drug therapy , Pleurotus/chemistry , Adipose Tissue/metabolism , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Atherosclerosis/etiology , Atherosclerosis/prevention & control , Biological Products/pharmacology , Chitin/pharmacology , Eating/drug effects , Fatty Liver/etiology , Fatty Liver/prevention & control , Hyperlipidemias/etiology , Hyperlipidemias/prevention & control , Lipids/blood , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Obesity/blood , Obesity/complications , Rats, Sprague-Dawley , Superoxide Dismutase/blood
20.
Int J Biol Macromol ; 163: 2097-2112, 2020 Nov 15.
Article En | MEDLINE | ID: mdl-32949625

Chitosan is an antimicrobial, biodegradable and biocompatible natural polymer, commercially derived from the partial deacetylation of chitin. Currently modified chitosan has occupied a major part of scientific research. Modified chitosan has excellent biotic characteristics like biodegradation, antibacterial, immunological, metal-binding and metal adsorption capacity and wound-healing ability. Chitosan is an excellent candidate for drug delivery, food packaging and wastewater treatment and is also used as a supporting object for cell culture, gene delivery and tissue engineering. Modification of pure chitosan via grafting improves the native properties of chitosan. Chitosan grafted copolymers exhibit high significance and are extensively used in numerous fields. In this review, modifications of chitosan through several graft copolymerization techniques such as free radical, radiation, and enzymatic were reported and the properties of grafted chitosan were discussed. This review also discussed the applications of grafted chitosan in the fields of drug delivery, food packaging, antimicrobial, and metal adsorption as well as dye removal.


Chitin/chemical synthesis , Chitosan/chemical synthesis , Tissue Engineering , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Chitin/chemistry , Chitin/therapeutic use , Chitosan/chemistry , Chitosan/therapeutic use , Drug Delivery Systems , Humans , Polymerization , Polymers/chemistry , Polymers/therapeutic use , Wound Healing/genetics
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