INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jingqiu He-Yang,Wenting Zhang,Jie Liu,Peng Xue,Xiaoying Zhou
Necrotizing enterocolitis (NEC), a devastating infant disease characterized by severe intestinal necrosis, its pathogenesis is poorly understood, but appears to be multifactorial and highly associated with immaturity of gastrointestinal tract and immature innate-immune system. Breast-milk is effective strategy to protect infants against NEC. This study is using a NEC rat model to investigate the pathological mechanism of NEC involved intestinal-damages, and the therapeutic mechanism of sialylated human milk oligosaccharides (SHMOs) on NEC rats; also using cell model to investigate the effects of SHMOs on colon-epithelial cells (Caco-2) in-vitro . Extraction and characterization of SHMOs from breast milk, establishment of a NEC rat model, histopathological analysis and mast cell accounting of the terminal ileum were taken; The levels of DPPI, TLR4, IL-6, TNF-α, MMP-2/9 and glutathione were measured using various methods. Caco-2 cells were pre-treated with SHMOs and cultured with LPS, histamine, chymase or DPPI, cell viabilities and mitochondrial membrane potential were examined; flow cytometry was used to detect cell cycle. The accumulation of mast cells was found in the ileum of NEC rats, but prohibited by SHMOs treatment; the increased levels of TLR4, DPPI, IL-6, TNF-α, MMP-2/9 in NEC ileum were suppressed by SHMOs in-vivo . SHMOs prevented Caco-2 cells from LPS, histamine, chymase induced damages by surviving cell viability, regulating G0/G1 and S phase in cell cycles, and increasing mitochondrial membrane potential. These findings provide a new insight into the pharmacological mechanism of SHMOs treatment for NEC and suggest that SHMOs needs well attention for therapeutic aims.
研究领域:
儿科
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胃肠病学
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免疫学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
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IF 3.571
Yu Lu,Jie Liu,Yue Jia,Yuerong Yang,Qinghui Chen,Lujia Sun,Shuang Song,Linjuan Huang,Zhongfu Wang
Human milk oligosaccharides are complex carbohydrates with multibiofunctional health benefits to newborns. Human milk free oligosaccharides (HMOs) are well characterized. However, changes in the N/O-glycome during lactation are poorly reported. Herein, we qualitatively and quantitatively investigated N/O-glycome profiles and their alteration in human milk at different lactation stages. N-Glycans were mainly fucosylated and nonsialylated, nonfucosylated throughout lactation. O-Glycans mainly consisted of sialylated and nonsialylated, nonfucosylated in colostrum and transitional milk, and fucosylated and nonfucosylated, nonsialylated in mature milk. Fucosylated and sialylated N-glycans gradually decreased and increased, respectively, as lactation progressed; O-glycans showed the reverse. Interestingly, changes in HMO abundance decreased during lactation, complementing HMG N/O-glycome changes. In conclusion, temporal HMG glycosylation changes provide the groundwork for developing infant formula that is closer to breast milk at different lactation stages.
研究领域:
生物化学
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营养学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Xi Gao,Yu Lu,Ming Wei,MeiFang Yang,CaiXia Zheng,Chengjian Wang,Ying Zhang,Linjuan Huang,Zhongfu Wang
The functional role of human milk oligosaccharides (HMOs) is closely associated with their type, composition, and structure. However, a detailed analysis of HMOs is difficult because neutral oligosaccharides (NHMOs) are mixed with sialylated oligosaccharides (SHMOs) in milk. Here, NHMOs were separated from SHMOs by DEAE-52 anion chromatography, and lactose was removed by graphite carbon solid-phase extraction. Lactose-free NHMOs were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) based on Girard’s reagent P on-target derivatization (GPOD), and SHMOs were analyzed by MALDI-TOF-MS following selective sialic acid derivatization and GPOD. Sixty-four oligosaccharides were detected: 36 NHMOs, of which 28 were fucosylated, and 28 SHMOs, of which 8 with α-2,3-linked monosialic acid, 2 with α-2,3-linked disialic acid, 10 with α-2,6-linked monosialic acid, 2 with α-2,6-linked disialic acid, and 5 with both α-2,3- and α-2,6-linked disialic acid. These findings provide the groundwork for further characterization of the structure and activity of HMOs.
研究领域:
生物化学
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营养学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
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IF 5.895
Wanjun Jin,Yu Lu,Cheng Li,Meiyi Zou,Qinghui Chen,Lijing Nan,Ming Wei,Chengjian Wang,Linjuan Huang,Zhongfu Wang
Sialylated human milk oligosaccharides (SHMOs) possess unique biological activities. Qualitative and quantitative analyses of SHMOs at different lactation stages are limited by interference from neutral oligosaccharides, glycan structural complexity, and low detection sensitivity. Herein, our previously developed glycoqueuing strategy was improved and applied to enable an isomer-specific quantitative comparison of SHMOs between colostrum milk (CM) and mature milk (MM). A total of 49 putative structures were determined, including 1 α2,6-linked and 13 α2,3-linked isomers separated from seven newly discovered SHMO compositions. The content of most oligosaccharides was more than 50% lower in MM than in CM, and α2,3-sialylation was observed in 43.74% of SHMOs from CM and 22.95% of SHMOs from MM. Finally, the fucosylation level of the SHMOs increased from 16.45 to 22.28% with prolonged lactation. These findings provide the basis for further studies on the structure–activity relationship of SHMOs and a blueprint to improve infant formula.
研究领域:
生物化学
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营养学
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儿科医学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2024
·Vol. 14
·期 25
·17397-17405
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IF 3.9
Yiran Wu,Yunze Sun,Caixia Pei,Xinlv Peng,Xianming Liu,Eika W. Qian,Yuguang Du,Jian-Jun Li
Glycans, along with proteins, nucleic acids, and lipids, constitute the four fundamental classes of biomacromolecules found in living organisms. Generally, glycans are attached to proteins or lipids to form glycoconjugates that perform critical roles in various biological processes. Automatic synthesis of glycans is essential for investigation into structure–function relationships of glycans. In this study, we presented a method that integrated magnetic bead-based manipulation and modular chemoenzymatic synthesis of human milk oligosaccharides (HMOs), on a DMF (Digital Microfluidics) platform. On the DMF platform, enzymatic modular reactions were conducted in solution, and purification of products or intermediates was achieved by using DEAE magnetic beads, circumventing the intricate steps required for traditional solid-phase synthesis. With this approach, we have successfully synthesized eleven HMOs with highest yields of up to >90% on the DMF platform. This study would not only lay the foundation for OPME synthesis of glycans on the DMF platform, but also set the stage for developing automated enzymatic glycan synthesizers based on the DMF platform.
研究领域:
生物化学
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化学工程
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生物技术
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Chengqiang Li,Zhuoning Cao,Hong Jiang,Francesco Secundo,Xiangzhao Mao
β-N-Acetylhexosaminidases have attracted much attention in the enzymatic synthesis of lacto-N-triose II (LNT2) as a backbone precursor of human milk oligosaccharides (HMOs). In this study, a novel glycoside hydrolase (GH) 20 family β-N-acetylhexosaminidase, FlaNag2353, from Flavobacterium algicola was biochemically characterized and applied to synthesize LNT2. FlaNag2353 displayed optimal activity to p-nitrophenyl N-acetyl-β-d-glucosaminide (pNP-GlcNAc) at 40 °C and pH 8.0. In addition to its excellent hydrolysis activity toward pNP-GlcNAc and chitooligosaccharides, FlaNag2353 showed trans-glycosylation activity. Under conditions of pH 9.0 and 55 °C for 2 h and utilizing 200 mM lactose and 10 mM pNP-GlcNAc, FlaNag2353 synthesized LNT2 with a conversion ratio of 4.15% calculated from pNP-GlcNAc. Moreover, when applied to LNT2 synthesis with 10 mM pNP-GlcNAc and 9.7% (w/v) industrial waste whey powder, FlaNag2353 achieved a conversion ratio of 2.39%. This study has significant implications for broadening the applications of GH20 β-N-acetylhexosaminidases and promoting the high-value utilization of whey powder.
研究领域:
生物化学
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酶学
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食品科学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Journal of Future Foods
·
2025
·
IF 7.2
Fangqin Xiang,Yuxing Li,Yumeng Zhang,Yuning Yang,Bailiang Li,Sufang Duan
Ulcerative colitis (UC) is a chronic disease with an increasing incidence worldwide. 2’-Fucosyllactose (2’-FL) is the most abundant fucosylated neutral human milk oligosaccharides (HMOs), accounting for approximately 31% of the total HMOs content, and shows considerable potential in alleviating UC. This study aimed to investigate the therapeutic effect of 2’-FL on DSS-induced colitis in mice and explore its potential mechanisms. The results showed that HMO alleviated the symptoms of DSS-induced colitis in mice by alleviating weight loss, reducing the disease activity index (DAI), increasing the length of the mouse colon and improving the spleen index; HMO enhanced intestinal barrier function by repairing colon tissue damage, reducing intestinal permeability (DAO and D-LA), increasing the expression of Tight junctions (TJs), promoting the production of anti-inflammatory factor IL-10, and inhibiting cytokines (IL-1β, IL-6, and TNF-α). In addition, the activation of the colitis-related NF-κB pathway was significantly inhibited after HMO intervention. Furthermore, metagenomic analysis revealed that HMO intervention in colitis mice significantly increased the relative abundance of Bacteroidetes, Parabacteroidetes, Parabacteroides and Prevotella .; non-targeted metabolomics analysis demonstrated that HMO modulated the host's bile acid metabolism by preserving the level of deoxycholic acid. To further investigate the molecular mechanisms affecting bile acid metabolism, enzyme scanning was performed based on species-level genome enriched in different groups. The results showed that the bacteria mainly enriched in the HMO treatment group showed greater potential in encoding bile salt hydrolases (BSH) responsible for the dissociation of primary bile acids and 7α-hydroxysteroid dehydrogenases (7α-HSDs) that produce secondary bile acids. In summary, this study showed that HMO intervention changed the composition of the intestinal flora, and the specially enriched intestinal microorganisms regulated the host's secondary bile acid metabolism, thereby effectively alleviating colon inflammation in mice.
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产品关联
DOI
高影响因子
ACS Synthetic Biology
·
2025
·
IF 3.9
Ruoyu Jiao,Chuanyu Fu,Jie Zheng,Xing Zhang
Carbohydrates are among the most essential biomolecules for human survival, and their synthesis has garnered considerable research attention. Enzymatic synthesis provides significant advantages by addressing the challenges in controlling stereoselectivity and regioselectivity. However, broader application is hindered by labor-intensive purification procedures and substantial product loss during repeated vessel transfers. The implementation of solid-phase strategies in enzymatic carbohydrate synthesis reduces material transfer losses and streamlines downstream purification. Nevertheless, integrating enzymatic reactions with solid-phase systems presents significant compatibility issues, such as steric hindrance and restricted substrate accessibility, which diminish enzymatic efficiency and reduce productivity. To address these limitations, we developed a universal and efficient platform termed SWITCH (support-based workflow integrated temperature-sensitive enzymatic carbohydrate synthesis). This platform utilizes a temperature-responsive polymer as the support, where substrates are immobilized via click chemistry. This design enables glycan synthesis under homogeneous aqueous conditions, enhancing enzymatic accessibility and catalytic activity. Upon heating, the polymer undergoes a phase transition and precipitates from solution, enabling product isolation by filtration without organic solvents. On this platform, by integrating diverse enzyme modules to construct distinct glycosylation pathways, we successfully built a library of structurally defined glycans, including human milk oligosaccharides and glycosaminoglycans. This platform streamlines precise glycan synthesis and establishes a foundation for advancing glycoscience and biopharmaceutical applications.
研究领域:
碳水化合物化学
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酶促合成
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固相化学
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糖科学
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生物制药
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生物有机化学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Jiayue Tang,Dan Yao,Jiahe Zhao,Maolin Tu
Human milk oligosaccharides (HMOs) are significant constituents of breast milk and have potential anti-inflammatory bioactivities. We compared the immunomodulatory effects of lacto-N-biose I (LNB), lacto-N-triose II (LNT II), galacto-oligosaccharides (GOS), and their combinations (GOS+LNB, GOS+LNT II, LNB+LNT II, m/m=1:1) in lipopolysaccharide-induced RAW264.7 macrophages. LNT II and LNB+LNT II efficiently inhibited inflammation-related gene expression and enhanced phagocytosis and anti-inflammatory ability, which may be attributed to their N-acetylglucosamine structure. Three milk powder prototypes (control, LNT II, and LNB+LNT II) were formulated and characterized, exhibiting favorable physicochemical properties. In-vitro simulated digestion coupled with caucasian colon adenocarcinoma (Caco-2) inflammation model demonstrated that the milk powder digestives inhibited tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) release while promoting interleukin-10 (IL-10) production. The digestives of the three milk powders could also inhibit the decrease in transmembrane electrical resistance and the increase in intestinal permeability, playing a crucial role in maintaining intestinal homeostasis. This study will contribute to the functional evaluation and product development of HMOs and inform milk powder design.
研究领域:
营养学
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免疫学
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食品科学
·
药理学
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产品关联
DOI
高影响因子
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