CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Shuxin Jiang,Huanan Yin,Xiaohui Qi,Weiguo Song,Weiwei Shi,Jiaojiao Mou,Jie Yang
Sea cucumbers were nutritional food and traditional Chinese medicine. In this study, fucosylated chondroitin sulfate from sea cucumber Stichopus chloronotus (fCS- Sc ), a potential anticoagulant agent and immunological adjuvant, was investigated for its immune activation effects on RAW 264.7 macrophage for the first time. The results indicated that fCS- Sc could significantly promote the proliferation, the pinocytic activity of RAW 264.7 cells, and the production of NO, TNF-α, IL-1β, and IL-6. The fluorescence labeling assay indicated that fCS- Sc could bind to the macrophage. Moreover, the specific pattern recognition receptor inhibition assays showed that toll-like receptor 4 (TLR4) and TLR2 were involved in the recognition of fCS- Sc . Western blot assays indicated that fCS- Sc could induce degradation of cytoplasm IκB-α, and promotion of NF-κB p65 subunit translocation to nucleus, leading to a functional improvement of macrophage through NF-κB pathway. The results suggested that fCS- Sc might served as a promising candidate of immunomodulator.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
·
IF 4.784
Xingyu Lu,Qian Zhong,Jian Liu,Fulin Yang,Chenghui Lu,Huan Xiong,Sha Li,Yibo Zhu,Lingtian Wu
Chondroitinase ABC I (ChSase ABC I) is a key enzyme of chondroitin sulfate (CS) degradation and widely used for CS detection in the medicine filed. However, the recombinant ChSase ABC I was weakly expressed in Escherichia coli because the forms of it were mostly inclusion bodies. In this study, a signal peptide ( pel B) was used for the soluble form expression of ChSase ABC I in E. coli . Then the culture condition for ChSase ABC I expression was optimized through response surface methodology. Results revealed that the expression level of ChSase ABC I in a 7.5 L fermentor (29.03 mL −1 ) was approximately 1.65-fold higher than that of the shake flask level (17.55 mL −1 ). The enzymatic properties and kinetic constants of recombinant ChSase ABC I were also studied. Recombinant ChSase ABC I was also used to detect the specific disaccharides content of CS from different sources. This study not only eliminates the problem of the enzyme expressed as an inclusion body, but also solves the current problem of expensive ChSase ABC. In a word, it would be an ideal strategy for ChSase ABC high-efficiency expression and a great method to detect specific disaccharides of CS in biomedical field.
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CARBOHYDRATE POLYMERS
·
2019
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IF 6.044
Lufeng Yan,Danli Wang,Mengshan Zhu,Yanlei Yu,Fuming Zhang,Xingqian Ye,Robert J. Linhardt,Shiguo Chen
Fucosylated chondroitin sulfate (FCS) oligosaccharides of specific molecular weight have shown potent anticoagulant activities with selectivity towards intrinsic factor Xase complex. However, the preparation of FCS oligosaccharides by traditional methods requires multiple purification steps consuming large amounts of time and significant resources. The current study focuses on developing a method for the rapid preparation of FCS oligomers from sea cucumber Pearsonothuria graeffei having 6–18 saccharide residues. The key steps controlling molecular weight ( M w) and purity of these FCS oligomers were evaluated. Structural analysis showed the resulting FCS oligomers were primarily l -Fuc3,4diS-α1,3- d -GlcA-β1,3-( d -GalNAc4,6diS-β1,4-[ l -Fuc3,4diS-α1,3-] d -GlcA-β1,3-) n d -anTal-ol4,6diS (n = 1˜5) accompanied by partial de-fucosylation and/or de-sulfation. In vitro and in vivo experiments demonstrate that these FCS oligomers selectively inhibit intrinsic factor Xase complex and exhibit remarkable antithrombotic activity without hemorrhagic and hypotension side effects. This method is suitable for large-scale preparation of FCS oligosaccharides as clinical anticoagulants.
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CARBOHYDRATE POLYMERS
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2018
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IF 5.158
Siying Zhang,Guanglian Zhou,Xiao Zhang,Dong Chen,Jian Liu,Xiumei Liu
A simple and sensitive flow injection chemiluminescence (FI-CL) method has been developed for the determination of chondroitin sulfate (CS). The method is based on the sensitization effect of enzymatic products of CS on the luminol-H 2 O 2 system. Experimental parameters affecting FI-CL method such as concentrations of luminol, H 2 O 2 and NaOH and the standing time of luminol alkaline solution were optimized. Under optimum conditions, the calibration plot between CS concentration and the change of CL intensity was linear in the range of 25 ng/mL∼250 ng/mL. The limit of detection (LOD) was 5 ng/mL and the average relative standard deviation (RSD) of CL intensity was 2.5%. The method was successfully applied to the quantitative analysis of CS concentration in drugs. Compared with the reported methods so far, the established method is simple, sensitive, accurate and rapid.
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CARBOHYDRATE RESEARCH
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2017
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IF 2.096
Jiaojiao Lu,Chunqing Ai,Li Guo,Yinghuan Fu,Chunyang Cao,Shuang Song
Because the glycosidic linkage of uronic acid is most resistant to acid, oligosaccharides may be formed during the acid hydrolysis of acidic polysaccharides . To take chondroitin sulfate (CS) as an example of acidic polysaccharides , the present study characterized the oligosaccharides released through acid hydrolysis and demonstrated their usefulness for structural confirmation. Acid hydrolysates of commercial standard CSs from shark cartilage and porcine bone were elucidated using HPLC-MS n after 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization , and altogether 11 di-, tri- and tetra-saccharides with or without sulfate/acetyl groups were identified by their multi-stage mass spectra. Meanwhile the trends of reaction yields of these oligosaccharides alone with trifluoroacetic acid (TFA) concentrations (0.1–2.0 M) were investigated, and 0.2 M TFA was recommended. Then three real samples, sturgeon backbone, porcine trachea and sea cucumber were analyzed, and their CSs were identified by detection of characteristic oligosaccharide fragments. The present study indicated that acid hydrolysis could provide information for acetyl substitution, sulfation and glycosidic linkages, and was helpful for the structural analysis of acidic polysaccharides.
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Lili Jin,Zhenhui Wang,Cheng Peng,Miao He,Feng Wang,Hongyan He,Changsheng Liu
Rheumatoid arthritis (RA), a persistent and debilitating chronic disease characterize by joint damage and deformity, significantly impairs the life quality of patients and presents challenges for conventional drug administration due to organ damage and unsatisfactory therapeutic outcomes. To address these challenges, this study introduces an innovative hydrogel cryo-microneedle patch (CMNP)-mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti-inflammatory drug melittin (MEL). This innovative approach not only circumvents organ impairment but also enhances patient compliance. The acute toxicity of MEL is effectively mitigated by electrostatic binding with CS molecules, forming MC complexes that induce apoptosis in fibroblast-like synoviocytes (FLS). The MC-loaded CMNPs (MC@CCMNPs) exhibit remarkable therapeutic capacity with a notably meliorated joint damage and suppressed arthritis severity in the RA rat model. Therefore, MC@CCMNPs emerge as a promising anti-inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.
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CARBOHYDRATE RESEARCH
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2018
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IF 2.074
Wenwei Han,Quancai Li,Youjing Lv,QingChi Wang,Xia Zhao
The sulfation pattern plays a crucial role in chondroitin sulfate (CS) biological activity, and preparation of CS with defined structure is essential for accurate pharmacological study. In this study, we focused on the preparation of regioselective 4- O /6- O -desulfated CS derived from porcine, employing a dimethyl sulfoxide-methanol (DMSO-MeOH) method and an N-methyl-N-(trimethylsilyl) -trifluoroacetamide (MTSTFA) method CS, respectively. Results showed that the sulfate at C4 position (4- O -S) of N-acetylgalactosamine (GalNAc) was selectively removed by the DMSO-MeOH method, and the sulfate at C6 position (6- O -S) of GalNAc was selectively removed by the MTSTFA method. Structures of desulfated CS were characterized by means of FT-IR, NMR and disaccharide composition analysis. The preparations of regioselective 4- O /6- O -desulfated CS are powerful for the study of structure-activity relationship of CS.
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Pharmaceutics
·
2025
·Vol. 17
·期 3
·351
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IF 5.5
Xunzhi Liu,Changlong Fang,Hongling Yu,Lu Huang,Jiaxing Feng,Shiqin Luo,Li Song,Mengying Wu,Yulu Tan,Jianxia Dong,Tao Gong,Peihong Xiao
Background: Activated hepatic stellate cells (aHSCs) play a significant role during the onset of hepatic fibrosis, ultimately leading to excessive deposition of extracellular matrix (ECM) and other typical pathological features, and thus have become a popular target for the treatment of hepatic fibrosis. However, current aHSC-centric therapy strategies achieve unsatisfactory results, mainly due to the lack of approved anti-fibrosis drugs and sufficiently efficient aHSC-targeted delivery systems. In this study, our aim was to develop an Imatinib-loaded nanoparticle delivery system based on a chondroitin sulfate derivative to enhance aHSC targeting efficiency, improve the therapeutic effect for hepatic fibrosis, and investigate the underlying mechanism.Methods: The carboxyl group of chondroitin sulfate and the amino group of 1-hexadecylamine were linked by an amide bond in this study to produce the amphiphilic carrier CS-HDA. Then, the Imatinib-loaded nanoparticles (IM-CS NPs) were designed to efficiently target aHSCs through CD44-mediated endocytosis and effectively inhibit HSC overactivation via PDGF and TGF-β signaling pathways.Results: Both in vitro cellular uptake experiments and in vivo distribution experiments demonstrated that CS-HDA-modified nanoparticles (IM-CS NPs) exhibited a better targeting ability for aHSCs, which were subsequently utilized to treat carbon tetrachloride-induced hepatic fibrosis mouse models. Finally, significant fibrosis resolution was observed in the carbon tetrachloride-induced hepatic fibrosis mouse models after tail vein injection of the IM-CS NPs, along with their outstanding biocompatibility and biological safety.Conclusions: IM-loaded NPs based on an amphiphilic CS derivative have remarkable antifibrotic effects, providing a promising avenue for the clinical treatment of advanced hepatic fibrosis.
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Acta Biomaterialia
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2017
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IF 6.319
Wenqi Chen,Yong Liu,Xiao Liang,Yu Huang,Quanshun Li
Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4 h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest , and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. Statement of Significance The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti -proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti -migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors.
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CARBOHYDRATE POLYMERS
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2019
·
IF 6.044
Xueqing Zhang,Ya Ma,Lijun Ma,Menghang Zu,Heliang Song,Bo Xiao
Orally targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for minimizing the symptoms of ulcerative colitis (UC). In this investigation, we encapsulated curcumin (CUR) into polymeric nanoparticles (NPs), and conjugated chondroitin sulfate (CS) to their surfaces. The resulting CS-NPs had an average diameter of 281 nm, monodisperse size distribution and negatively charged surface. Cell experiments indicated that these NPs showed excellent biocompatibility, and yielded significantly higher cell internalization efficiency in Raw 264.7 macrophages than their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-NPs). Moreover, CS-NPs exhibited a dramatically stronger capacity to inhibit the secretion of the major pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-NPs. In vivo experiments revealed that oral administration of chitosan/alginate hydrogel embedding CS-NPs achieved better therapeutic outcomes against UC comparied with CUL-NPs. Collectively, our results demonstrated that CS-NP-embedded hydrogel held a great promise to be developed as a macrophage-targeted drug delivery system for UC treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiao Qiao,Jie Li,Chunying Tao,Meiyang Yang,Weijun Chen,Lipeng Qiu,Huiming Tu
Studies have shown that inflammation is closely linked to the cancer development, and the patients with inflammatory bowel disease (IBD) have a higher risk of colon cancer. Celecoxib (CXB) and camptothecin (CPT) showed potential treatment for IBD and colon cancers, respectively. However, their applications are limited by synchronous delivery, water insolubility, and off-target side effects. Herein, a glutathione (GSH) responsive chondroitin sulfate A (CSA)-SS-CXB micelle loaded with CPT (CSA-SS-CXB@CPT) was prepared as a targeted system to treat colon cancer by anti-inflammatory and antitumor synergistic effect. Specifically, CSA had tumor tumor-targeting effect due to colon cancer lesion-high expression of CD44 receptors. In vitro results verified that CSA-SS-CXB@CPT selectively internalized into colon cancer HT-29 cells and had strong reactive oxygen species (ROS) elimination ability. The CSA-SS-CXB@CPT could rapidly release CXB and CPT in the tumor microenvironment for playing an anti-tumor role. In vivo experiments illustrated that CSA-SS-CXB@CPT significantly targeted tumor tissues and suppressed tumor growth without producing serious side effects in tumor-bearing nude mice. Therefore, this work provides an opportunity for targeted co-delivery of anti-inflammatory and chemotherapy drugs to treat colon cancer.
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CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Lei Xu,Fenbo Ma,Frankie K.L. Leung,Chenghe Qin,William W. Lu,Bin Tang
Bone defects caused by trauma have become increasingly common in aged populations. Clinically, because of the relatively decreased bone healing capacity compared with the youth adults, bone defect repair in the elderly remains challenging. The development of effective biomaterials targeted at bone defects in the elderly is a key component of bone-tissue engineering strategies. However, little attention has been paid to bone regeneration in the elderly. Here, we developed a new scaffold chitosan-Strontium chondroitin sulfate (CH-SrCS) and evaluated its effect on improving bone regeneration. We find that the CH-SrCS scaffold displayed positive effects on downregulation of inflammation and osteoclastogenesis related mRNA expressions while demonstrating a significant increase in the expression level of BMP2. Finally, we show that the bone defects healing effects as assessed using an aged rats' bone defects model. Ultimately, this work also provides insights into the design of effective biomaterials targeted at bone defects in the elderly.
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