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Article ; Online: In Silico

Li, Jiaqing / Xu, Tong / Zheng, Yalan / Liu, Dongdong / Zhang, Chen / Li, Jianjun / Wang, Zhuo A / Du, Yuguang

2024 Volume 96, Issue 12, Page(s) 5056–5064

Abstract: Aptamer-based detection targeting glycoconjugates has attracted significant attention for its remarkable potential in identifying structural changes in saccharides in different stages of various diseases. However, the challenges in screening aptamers for ...

Abstract	Aptamer-based detection targeting glycoconjugates has attracted significant attention for its remarkable potential in identifying structural changes in saccharides in different stages of various diseases. However, the challenges in screening aptamers for small carbohydrates or glycoconjugates, which contain highly flexible and diverse glycosidic bonds, have hindered their application and commercialization. In this study, we investigated the binding conformations between three glycosidic bond-containing small molecules (GlySMs; glucose,
MeSH term(s)	Glycosides ; Aptamers, Nucleotide/chemistry ; DNA, Single-Stranded ; Binding Sites ; Glycoconjugates ; SELEX Aptamer Technique
Chemical Substances	Glycosides ; Aptamers, Nucleotide ; DNA, Single-Stranded ; Glycoconjugates
Language	English
Publishing date	2024-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.4c00927
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Article ; Online: In Silico Selection and Validation of High-Affinity ssDNA Aptamers Targeting Paromomycin

Li, Jiaqing / Liu, Yangyang / Liu, Dongdong / Xu, Tong / Zhang, Chen / Li, Jianjun / Wang, Zhuo A. / Du, Yuguang

Analytical Chemistry. 2023 June 29, v. 95, no. 27 p.10405-10413

2023

Abstract: Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan- ... ...

Abstract	Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan-specific aptamers can be developed for challenging applications such as cancer targeting; however, the high flexibility of glycosidic bonds and scarcity of studies on glycan–aptamer binding mechanisms increased the difficulty of screening. In this work, the model of interactions between glycans and ssDNA aptamers synthesized based on the sequence of rRNA genes was developed. Our simulation-based approach revealed that paromomycin as a representative example of glycans is preferred to bind base-restricted stem structures of aptamers because they are more critical in stabilizing the flexible structures of glycans. Combined experiments and simulations have identified two optimal mutant aptamers. Our work would provide a potential strategy that the glycan-binding rRNA genes could act as the initial aptamer pools to accelerate aptamer screening. In addition, this in silico workflow would be potentially applied in the more extensive in vitro development and application of RNA-templated ssDNA aptamers targeting glycans.
Keywords	analytical chemistry ; biosynthesis ; computer simulation ; disease diagnosis ; glycosylation ; models ; mutants ; oligonucleotides ; polysaccharides
Language	English
Dates of publication	2023-0629
Size	p. 10405-10413.
Publishing place	American Chemical Society
Document type	Article ; Online
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.3c01575
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Article ; Online: In Silico

Li, Jiaqing / Liu, Yangyang / Liu, Dongdong / Xu, Tong / Zhang, Chen / Li, Jianjun / Wang, Zhuo A / Du, Yuguang

Analytical chemistry

2023 Volume 95, Issue 27, Page(s) 10405–10413

Abstract	Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan-specific aptamers can be developed for challenging applications such as cancer targeting; however, the high flexibility of glycosidic bonds and scarcity of studies on glycan-aptamer binding mechanisms increased the difficulty of screening. In this work, the model of interactions between glycans and ssDNA aptamers synthesized based on the sequence of rRNA genes was developed. Our simulation-based approach revealed that paromomycin as a representative example of glycans is preferred to bind base-restricted stem structures of aptamers because they are more critical in stabilizing the flexible structures of glycans. Combined experiments and simulations have identified two optimal mutant aptamers. Our work would provide a potential strategy that the glycan-binding rRNA genes could act as the initial aptamer pools to accelerate aptamer screening. In addition, this
MeSH term(s)	Paromomycin ; DNA, Single-Stranded ; Aptamers, Nucleotide/chemistry ; Computer Simulation ; Polysaccharides ; SELEX Aptamer Technique
Chemical Substances	Paromomycin (61JJC8N5ZK) ; DNA, Single-Stranded ; Aptamers, Nucleotide ; Polysaccharides
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.3c01575
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Article ; Online: Variations in metabolic enzymes cause differential changes of heparan sulfate and hyaluronan in high glucose treated cells on chip.

Wei, Jinhua / Liu, Dongdong / Xu, Tong / Zhu, Limeng / Jiao, Siming / Yuan, Xubing / Wang, Zhuo A / Li, Jianjun / Du, Yuguang

International journal of biological macromolecules

2023 Volume 253, Issue Pt 1, Page(s) 126627

Abstract: Glycocalyx dysfunction is believed as the first step in diabetic vascular disease. However, few studies have systematically investigated the influence of HG on the glycocalyx as a whole and its major constituent glycans towards one type of cell. ... ...

Abstract	Glycocalyx dysfunction is believed as the first step in diabetic vascular disease. However, few studies have systematically investigated the influence of HG on the glycocalyx as a whole and its major constituent glycans towards one type of cell. Furthermore, most studies utilized traditional two-dimensional (2D) cultures in vitro, which can't provide the necessary fluid environment for glycocalyx. Here, we utilized vascular glycocalyx on chips to evaluate the changes of glycocalyx and its constituent glycans in HG induced HUVECs. Fluorescence microscopy showed up-regulation of hyaluronan (HA) but down-regulation of heparan sulfate (HS). By analyzing the metabolic enzymes of both glycans, a decrease in the ratio of synthetic/degradative enzymes for HA and an increase in that for HS were demonstrated. Two substrates (UDP-GlcNAc, UDP-GlcA) for the synthesis of both glycans were increased according to omics analysis. Since they were firstly pumped into Golgi apparatus to synthesize HS, less substrates may be left for HA synthesis. Furthermore, the differential changes of HA and HS were confirmed in vessel slides from db/db mice. This study would deepen our understanding of impact of HG on glycocalyx formation and diabetic vascular disease.
MeSH term(s)	Mice ; Animals ; Hyaluronic Acid/metabolism ; Heparitin Sulfate/metabolism ; Diabetic Angiopathies ; Glucose ; Uridine Diphosphate
Chemical Substances	Hyaluronic Acid (9004-61-9) ; Heparitin Sulfate (9050-30-0) ; Glucose (IY9XDZ35W2) ; Uridine Diphosphate (58-98-0)
Language	English
Publishing date	2023-09-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.126627
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Article ; Online: Unveiling the inverse antimicrobial impact of a hetero-chitooligosaccharide on Candida tropicalis growth and biofilm formation.

Liu, Yangyang / Li, Ruilian / Zhang, Yuchen / Jiao, Siming / Xu, Tong / Zhou, Yuhang / Wang, Yujing / Wei, Jinhua / Du, Wei / Fujita, Morihisa / Du, Yuguang / Wang, Zhuo A

Carbohydrate polymers

2024 Volume 333, Page(s) 121999

Abstract: Chitosan and chitooligosaccharide (COS) are renowned for their potent antimicrobial prowess, yet the precise antimicrobial efficacy of COS remains elusive due to scant structural information about the utilized saccharides. This study delves into the ... ...

Abstract	Chitosan and chitooligosaccharide (COS) are renowned for their potent antimicrobial prowess, yet the precise antimicrobial efficacy of COS remains elusive due to scant structural information about the utilized saccharides. This study delves into the antimicrobial potential of COS, spotlighting a distinct hetero-chitooligosaccharide dubbed DACOS. In contrast to other COS, DACOS remarkably fosters the growth of Candida tropicalis planktonic cells and fungal biofilms. Employing gradient alcohol precipitation, DACOS was fractionated, unveiling diverse structural characteristics and differential impacts on C. tropicalis. Notably, in a murine model of systemic candidiasis, DACOS, particularly its 70 % alcohol precipitates, manifests a promotive effect on Candida infection. This research unveils a new pathway for exploring the intricate nexus between the structural attributes of chitosan oligosaccharides and their physiological repercussions, underscoring the imperative of crafting chitosan and COS with meticulously defined structural configurations.
MeSH term(s)	Animals ; Mice ; Candida tropicalis ; Chitosan/pharmacology ; Chitosan/chemistry ; Anti-Infective Agents ; Antifungal Agents/pharmacology ; Biofilms ; Oligosaccharides
Chemical Substances	oligochitosan ; Chitosan (9012-76-4) ; Anti-Infective Agents ; Antifungal Agents ; Oligosaccharides
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2024.121999
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Article ; Online: Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo.

Wang, Yujie / Wen, Rong / Liu, Dongdong / Zhang, Chen / Wang, Zhuo A / Du, Yuguang

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 8

Abstract: Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide ( ...

Abstract	Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Body Weight/drug effects ; Caco-2 Cells ; Chitosan/pharmacology ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/genetics ; Colitis/mortality ; Dextran Sulfate/administration & dosage ; Disease Models, Animal ; Gene Expression Regulation ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mucin-2/genetics ; Mucin-2/metabolism ; Occludin/genetics ; Occludin/metabolism ; Oligosaccharides/pharmacology ; Permeability/drug effects ; Signal Transduction ; Survival Analysis ; Tight Junctions/drug effects ; Tight Junctions/metabolism ; Tight Junctions/pathology
Chemical Substances	Anti-Inflammatory Agents ; MUC2 protein, human ; Mucin-2 ; OCLN protein, human ; Occludin ; Oligosaccharides ; Chitosan (9012-76-4) ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2021-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26082199
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Article ; Online: Unraveling synthesis of the cryptococcal cell wall and capsule.

Wang, Zhuo A / Li, Lucy X / Doering, Tamara L

Glycobiology

2018 Volume 28, Issue 10, Page(s) 719–730

Abstract: Fungal pathogens cause devastating infections in millions of individuals each year, representing a huge but underappreciated burden on human health. One of these, the opportunistic fungus Cryptococcus neoformans, kills hundreds of thousands of patients ... ...

Abstract	Fungal pathogens cause devastating infections in millions of individuals each year, representing a huge but underappreciated burden on human health. One of these, the opportunistic fungus Cryptococcus neoformans, kills hundreds of thousands of patients annually, disproportionately affecting people in resource-limited areas. This yeast is distinguished from other pathogenic fungi by a polysaccharide capsule that is displayed on the cell surface. The capsule consists of two complex polysaccharide polymers: a mannan substituted with xylose and glucuronic acid, and a galactan with galactomannan side chains that bear variable amounts of glucuronic acid and xylose. The cell wall, with which the capsule is associated, is a matrix of alpha and beta glucans, chitin, chitosan, and mannoproteins. In this review, we focus on synthesis of the wall and capsule, both of which are critical for the ability of this microbe to cause disease and are distinct from structures found in either model yeasts or the mammals afflicted by this infection. Significant research effort over the last few decades has been applied to defining the synthetic machinery of these two structures, including nucleotide sugar metabolism and transport, glycosyltransferase activities, polysaccharide export, and assembly and association of structural elements. Discoveries in this area have elucidated fundamental biology and may lead to novel targets for antifungal therapy. In this review, we summarize the progress made in this challenging and fascinating area, and outline future research questions.
MeSH term(s)	Capsules/metabolism ; Cell Wall/metabolism ; Cryptococcus neoformans/metabolism
Chemical Substances	Capsules
Language	English
Publishing date	2018-04-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1067689-2
ISSN	1460-2423 ; 0959-6658
ISSN (online)	1460-2423
ISSN	0959-6658
DOI	10.1093/glycob/cwy030
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Article ; Online: Recent Research and Application Prospect of Functional Oligosaccharides on Intestinal Disease Treatment.

Xu, Tong / Sun, Ruijie / Zhang, Yuchen / Zhang, Chen / Wang, Yujing / Wang, Zhuo A / Du, Yuguang

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 21

Abstract: The intestinal tract is an essential digestive organ of the human body, and damage to the intestinal barrier will lead to various diseases. Functional oligosaccharides are carbohydrates with a low degree of polymerization and exhibit beneficial effects ... ...

Abstract	The intestinal tract is an essential digestive organ of the human body, and damage to the intestinal barrier will lead to various diseases. Functional oligosaccharides are carbohydrates with a low degree of polymerization and exhibit beneficial effects on human intestinal health. Laboratory experiments and clinical studies indicate that functional oligosaccharides repair the damaged intestinal tract and maintain intestinal homeostasis by regulating intestinal barrier function, immune response, and intestinal microbial composition. Functional oligosaccharides treat intestinal disease such as inflammatory bowel disease (IBD) and colorectal cancer (CRC) and have excellent prospects for therapeutic application. Here, we present an overview of the recent research into the effects of functional oligosaccharides on intestinal health.
MeSH term(s)	Humans ; Inflammatory Bowel Diseases/drug therapy ; Intestines ; Homeostasis ; Oligosaccharides/therapeutic use
Chemical Substances	Oligosaccharides
Language	English
Publishing date	2022-11-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27217622
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Article: Establishment and application of a dynamic tumor-vessel microsystem for studying different stages of tumor metastasis and evaluating anti-tumor drugs

Jing, Bolin / Luo, Yong / Lin, Bingcheng / Li, Jianjun / Wang, Zhuo A / Du, Yuguang

RSC advances. 2019 May 31, v. 9, no. 30

2019

Abstract: Tumor metastasis is one of the main causes of cancer-related death, and it is difficult to study the whole process of tumor metastasis in vivo due to the complex physiological environment in the body. Therefore, it's crucial to develop simple and ... ...

Abstract	Tumor metastasis is one of the main causes of cancer-related death, and it is difficult to study the whole process of tumor metastasis in vivo due to the complex physiological environment in the body. Therefore, it's crucial to develop simple and physiologically relevant in vitro cancer models to study the metastasis process, especially different phases of tumor metastasis. A novel microfluidic tumor-vessel co-culture system was established to reproduce the different phases of cancer metastasis (proliferation, migration, intravasation and adherence) individually in vitro for the first time. It was observed that blood vessels with fluid flow had big impact on metastasis of liver cancer cells HepG2 and breast ones MDA-MB-231. In particular, it was found that both HepG2 and MDA-MB-231 cells migrated in the direction of “blood flow”. Furthermore, MDA-MB-231 cells invaded through paracellular mode disrupting the intercellular endothelial junctions, whereas HepG2 cells engaged in transcellular intravasation through transcellular process. Compared with traditional assays, much more potent inhibition of 5-fluorouracil (5-Fu) on different phases of tumor metastasis was observed on the microsystem. In summary, the microfluidic device yielded abundant information about each phase of tumor metastasis, and would provide a powerful platform for use in drug screening, toxicology studies, and personalized medicine in future.
Keywords	blood vessels ; breasts ; coculture ; death ; fluorouracil ; human cell lines ; liver neoplasms ; metastasis ; models ; neoplasm cells ; precision medicine ; screening ; toxicology
Language	English
Dates of publication	2019-0531
Size	p. 17137-17147.
Publishing place	The Royal Society of Chemistry
Document type	Article
ISSN	2046-2069
DOI	10.1039/c9ra02069a
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Article: Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

Jing, Bolin / Cheng, Gong / Li, Jianjun / Wang, Zhuo A / Du, Yuguang

Marine drugs. 2019 July 13, v. 17, no. 7

2019

Abstract: Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage( ...

Abstract	Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (F<inf>A</inf>) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (F<inf>A</inf> = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.
Keywords	absorption ; acetylation ; antineoplastic activity ; blood vessels ; chitooligosaccharides ; chitosan ; drugs ; human cell lines ; liver neoplasms ; metastasis ; neoplasm cells
Language	English
Dates of publication	2019-0713
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2175190-0
ISSN	1660-3397
ISSN	1660-3397
DOI	10.3390/md17070415
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