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Drug Metabolism and Pharmacokinetics Feb 2022Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main... (Review)
Review
Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main chain glucoses and the one nucleotide base. Dectin-1, one of the major receptors for β-glucans, is known to be expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells. This suggests that the above-mentioned complexes could deliver bound functional oligonucleotides (ODNs) including antisense (AS)-ODNs, small interfering RNA, and CpG-ODNs to the APCs. Analysis using a quartz crystal microbalance revealed that a complex consisting of SPG and dA with a phosphorothioate backbone was recognized by recombinant Dectin-1 protein. Treatment with this complex containing an AS-ODN for tumor necrosis factor alpha protected mice against lipopolysaccharide-induced hepatitis at a very low AS-ODN dose. Moreover, immunization with CpG-ODN/SPG complex and antigenic proteins induced potent antigen specific immune responses. The present review also represents peptide delivery by conjugation with dA and the preparation of a nanogel using DNA-DNA hybridization. These findings indicate that the delivery of a specific ODN using β-glucans could be used for treating various diseases caused by APCs and for activating antigen specific immune responses.
Topics: Animals; Antigen-Presenting Cells; Mice; Oligonucleotides; RNA, Small Interfering; Sizofiran; beta-Glucans
PubMed: 34896749
DOI: 10.1016/j.dmpk.2021.100434 -
Journal of Ovarian Research Mar 2020Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common... (Review)
Review
Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common therapeutic approaches in the treatment of cervical cancer, but because of their side effects and toxicity, researchers are trying to discovery alternative therapies. Beta-glucans, a group of glucose polymers that are derived from the cell wall of fungi, bacteria, and etc. it has been showed that beta-glucans have some anti-cancer properties which due to their impacts on adaptive and innate immunity. Along to these impacts, these molecules could be used as drug carriers. In this regard, the application of beta-glucans is a promising therapeutic option for the cancer prevention and treatment especially for cervical cancer. Herein, we have summarized the therapeutic potential of beta-glucans alone or as adjuvant therapy in the treatment of cervical cancer. Moreover, we highlighted beta-glucans as drug carriers for preventive and therapeutic purposes.
Topics: Carrier Proteins; Clinical Studies as Topic; Disease Management; Disease Susceptibility; Drug Evaluation, Preclinical; Female; Humans; Immunomodulation; Molecular Targeted Therapy; Myeloid-Derived Suppressor Cells; Protein Binding; Signal Transduction; Uterine Cervical Neoplasms; beta-Glucans
PubMed: 32138756
DOI: 10.1186/s13048-020-00626-7 -
Annals of the New York Academy of... Oct 2012Macrophage migration inhibitory factor (MIF) is a unique protein that participates in inflammation, immune responses, and cell growth. An array of in vitro and in vivo... (Review)
Review
Macrophage migration inhibitory factor (MIF) is a unique protein that participates in inflammation, immune responses, and cell growth. An array of in vitro and in vivo experiments has demonstrated that MIF is profoundly involved in the pathogenesis of acute and chronic inflammatory disorders, such as inflammatory bowel disease (IBD). Blockade of MIF bioactivities by either neutralizing anti-MIF antibodies or antagonists prevents inflammatory cytokine cascade, which strongly suggests that an anti-MIF therapeutic strategy is feasible for treatment of IBD. Recently, we developed a new therapeutic approach for IBD by administration of antisense MIF oligonucleotides in conjugation with schizophyllan (SPG), a member of the glucan family. SPG specifically binds Dectin-1 expressed in antigen-presenting cells (APCs), and the antisense MIF/SPG complex is incorporated into the cells. In in vivo experiments of colitis models in mice, we found that intraperitoneal administration of the complex ameliorated the clinical signs of colitis and improved the histological scores. This novel therapy designed to knock down the MIF production in APCs is expected to be clinically applicable for the treatment of IBD.
Topics: Animals; Dendritic Cells; Drug Delivery Systems; Gene Knockdown Techniques; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Intestinal Mucosa; Intramolecular Oxidoreductases; Lectins, C-Type; Macrophage Migration-Inhibitory Factors; Macrophages; Molecular Targeted Therapy; Oligonucleotides, Antisense; Sizofiran
PubMed: 23050964
DOI: 10.1111/j.1749-6632.2012.06735.x -
Japanese Journal of Cancer Research :... May 1993The inhibitory effects of a biological response modifier (BRM), sizofiran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various...
The inhibitory effects of a biological response modifier (BRM), sizofiran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various anticancer agents or irradiation were investigated. Sizofiran (10 mg/kg i.m.) inhibited SCEs induced by mitomycin C (2 mg/kg i.v.), adriamycin (20 mg/kg i.v.) and cyclophosphamide (20 mg/kg i.v.) by about 20%, respectively. Analysis of the SCEs in vivo after irradiation plus sizofiran indicated that SCE levels were significantly lower than those observed in mice exposed to irradiation without sizofiran. Moreover, the effects of sizofiran were dependent on the timing of administration. Our results indicated that sizofiran should be administered simultaneously or soon after irradiation in order to minimize damage. Sizofiran also markedly restored the bone marrow cell mitosis which had been suppressed by anticancer agents, and this action was closely correlated with the prevention of increase in SCEs. These results indicate that in addition to immunopotentiating activity, sizofiran may play a role in preventing chromosomal damage induced by cancer chemotherapy and radiotherapy.
Topics: Animals; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Carbohydrate Sequence; Male; Mice; Mice, Inbred C3H; Mitotic Index; Molecular Sequence Data; Sister Chromatid Exchange; Sizofiran
PubMed: 8320171
DOI: 10.1111/j.1349-7006.1993.tb00173.x -
Biochemical and Biophysical Research... May 2024Schizophyllan (SPG), a β-glucan from Schizophyllum commune, is recognized for its antioxidant, immunoregulatory, and anticancer activities. In this study, its effects...
Schizophyllan (SPG), a β-glucan from Schizophyllum commune, is recognized for its antioxidant, immunoregulatory, and anticancer activities. In this study, its effects on bone cells, particularly osteoclasts and osteoblasts, were examined. We demonstrated that SPG dose-dependently inhibited osteoclastogenesis and reduced gene expression associated with osteoclast differentiation. SPG also decreased bone resorption and F-actin ring formation. This inhibition could have been due to the downregulation of transcription factors c-Fos and nuclear factor of activated T cells 1 (NFATc1) via the MAPKs (JNK and p38), IκBα, and PGC1β/PPARγ pathways. In coculture, SPG lowered osteoclastogenic activity in calvaria-derived osteoblasts by reducing macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) expression. In addition, SPG slightly enhanced osteoblast differentiation, as evidenced by increased differentiation marker gene expression and alizarin red staining. It also exhibited antiresorptive effects in a lipopolysaccharide-induced calvarial bone loss model. These results indicated a dual role of SPG in bone cell regulation by suppressing osteoclastogenesis and promoting osteoblast differentiation. Thus, SPG could be a therapeutic agent for bone resorption-related diseases such as osteoporosis, rheumatoid arthritis, and periodontitis.
Topics: Humans; Osteoclasts; Sizofiran; NFATC Transcription Factors; Osteoblasts; Cell Differentiation; Bone Resorption; Osteogenesis; RANK Ligand
PubMed: 38604070
DOI: 10.1016/j.bbrc.2024.149860 -
Scientific Reports Sep 2018Schizophyllan (SCH) is a high molecular weight homopolysaccharide composed of a β-(1,3)-D-glucan main chain with branching β-(1,6)-bound D-glucose residues. It forms...
Schizophyllan (SCH) is a high molecular weight homopolysaccharide composed of a β-(1,3)-D-glucan main chain with branching β-(1,6)-bound D-glucose residues. It forms triple helices that are highly stable towards heat and extreme pH, which provides SCH with interesting properties for industrial and medical applications. The recombinant anti-SCH antibody JoJ48C11 recognizes SCH and related β-(1,6)-branched β-(1,3)-D-glucans, but details governing its specificity are not known. Here, we fill this gap by determining crystal structures of the antigen binding fragment (Fab) of JoJ48C11 in the apo form and in complex with the unbranched β-(1,3)-D-glucose hexamer laminarihexaose 3.0 and 2.4 Å resolution, respectively. Together with docking studies, this allowed construction of a JoJ48C11/triple-helical SCH complex, leading to the identification of eight amino acid residues of JoJ48C11 (Tyr27, His35, Trp47, Trp100, Asp105; Asp49, Lys52, Trp90) that contribute to the recognition of glucose units from all three chains of the SCH triple helix. The importance of these amino acids was confirmed by mutagenesis and ELISA-based analysis. Our work provides an explanation for the specific recognition of triple-helical β-(1,6)-branched β-(1,3)-D-glucans by JoJ48C11 and provides another structure example for anti-carbohydrate antibodies.
Topics: Antibodies; Antigens; Crystallography, X-Ray; Immunoglobulin Fab Fragments; Molecular Docking Simulation; Oligosaccharides; Sizofiran; beta-Glucans
PubMed: 30209318
DOI: 10.1038/s41598-018-31961-x -
Journal of Controlled Release :... Oct 2021Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune...
Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune cells is here described. In this approach, a macromolecular complex of oligonucleotides and the β-1,3-glucan schizophyllan (SPG) is selectively delivered to cells expressing a lectin receptor, Dectin-1, via SPG-Dectin-1 interaction. Detailed investigation of Dectin-1-expressing cells revealed that Dectin-1 is expressed in all subsets of monocytes as well as dendritic cell (DC) populations, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), in humans. The expression patterns in mice and humans are comparable, except for the expression in pDCs. The results indicate that Dectin-1 is expressed on cells capable of professional antigen presentation, except for B cells. We chose CD40 as a target gene for small interfering RNA (siRNA) as CD40 expression in antigen-presenting cells (APCs), particularly in DCs, plays critical roles in regulating immune responses. Dose-dependent cellular uptake of siCD40-SPG complexes was confirmed in cells expressing Dectin-1. Gene silencing activity was confirmed in vitro by the reduction of CD40 mRNA and by the site-specific cleavage of CD40 mRNA as determined by the 5' RNA ligase-mediated rapid amplification of cDNA ends (5'RLM-RACE) technique. In vivo activity of siCD40-SPG complexes was demonstrated as the reduced CD40 protein expression in monocytes and DCs in mice. Furthermore, the in vivo activity of siCD40-SPG targeting human CD40 was confirmed in cynomolgus monkeys by the 5'RLM-RACE technique. In conclusion, we have demonstrated the receptor-ligand binding-mediated delivery of siRNA targeting immune-regulating monocytes and DCs via the interaction of SPG and its receptor, Dectin-1. As monocytes and DCs play central roles in inducing and controlling immune responses, Dectin-1-targeted delivery of nucleic acids should provide a useful tool for developing drugs to treat a wide range of diseases, including autoimmune diseases, allergy, and cancer, as well as transplantation.
Topics: Animals; Dendritic Cells; Lectins, C-Type; Mice; Oligonucleotides; RNA, Small Interfering; Sizofiran; beta-Glucans
PubMed: 34530053
DOI: 10.1016/j.jconrel.2021.09.011 -
Internal Medicine (Tokyo, Japan) Nov 2002It has been reported that various types of immunoactivators can induce Graves' disease. We describe here a case of Graves' disease during treatment with sizofiran, an...
It has been reported that various types of immunoactivators can induce Graves' disease. We describe here a case of Graves' disease during treatment with sizofiran, an immunoactivator. A 42-year-old woman who had previously been in an euthyroid state with Hashimoto's thyroiditis, experienced thyrotoxicosis during continuous administration of sizofiran as immunotherapy for endometrial carcinoma. Since the TSH receptor-antibody was positive, and a thyroid scintigram showed diffuse goiter and high uptake, she was diagnosed as having Graves' disease. It is suggested that the administration of sizofiran may be one of the triggers of Graves' disease.
Topics: Adult; Antineoplastic Agents, Phytogenic; Female; Graves Disease; Humans; Sizofiran
PubMed: 12487171
DOI: 10.2169/internalmedicine.41.977 -
Molecular weight degradation and rheological properties of schizophyllan under ultrasonic treatment.Ultrasonics Sonochemistry Mar 2015Molecular weight degradation effects of schizophyllan (SPG) under ultrasonic treatments were investigated in this study. The degradation product was treated by alcohol...
Molecular weight degradation effects of schizophyllan (SPG) under ultrasonic treatments were investigated in this study. The degradation product was treated by alcohol fractional precipitation technology, and the molecular weight and rheological properties of ultrasonic-treated SPG (USPG) fractions were evaluated. Average molecular weight of SPG decreased significantly after ultrasonic treatments, and degradation product had more narrow distribution of molecular weight. The molecular weight degradation kinetics of SPG is adequately described by a second-order reaction. USPG fractions with different molecular weight were obtained by fractional precipitation for final alcohol concentration fractions 0-40%, 40-60% and 60-80%, respectively. USPG fractions had near-Newtonian flow behaviors, and USPG₈₀% exhibited viscous responses over the entire accessible frequency range. Therefore, ultrasonic treatment is a viable modification technology for SPG and other polymer materials with high molecular weight.
Topics: Kinetics; Molecular Weight; Rheology; Sizofiran; Ultrasonics
PubMed: 25263766
DOI: 10.1016/j.ultsonch.2014.09.008 -
Carbohydrate Polymers Jul 2020Schizophyllan is a natural polysaccharide that has shown great potential as enhanced oil recovery (EOR) polymer for high-temperature, high-salinity reservoirs....
Schizophyllan is a natural polysaccharide that has shown great potential as enhanced oil recovery (EOR) polymer for high-temperature, high-salinity reservoirs. Nevertheless, the adsorption behavior of schizophyllan over carbonate minerals remains ambiguous element towards its EOR applications. Here, we investigate the adsorption of schizophyllan on different carbonate minerals. The effect of mineral type, salinity, and background ions on adsorption is analyzed. Our results indicate the adsorption capacity is higher on calcite and dolomite compared to silica and kaolin and the adsorption capacity decreases with salinity. Moreover, the adsorption kinetics follows pseudo-second order mechanism regardless of the mineral type. Adsorption over calcite is diminished in presence of water structure making ions and enhanced in presence of structure breaking ion and in presence of urea. Gel permeation chromatography results reveal the preferential adsorption of longer chains. The adsorption over carbonate minerals proceed via complex formation between polymer molecule and mineral surface.
Topics: Adsorption; Kinetics; Minerals; Sizofiran
PubMed: 32475555
DOI: 10.1016/j.carbpol.2020.116263