INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Haiyong Pan,Bai Miao,Wenting Zheng,Lina Yang,He Liu
Polysaccharides derived from soybean seed coats exhibit diverse functional properties and significant application potential; however, their intestinal absorption and transport mechanisms remain poorly understood. This study investigates the molecular docking interactions of two soybean seed coat polysaccharides (NMSP and CSSP), extracted using different methods, with the MUC2 protein, and explores their absorption and transport properties using Caco-2 cell models. Molecular dynamics simulations revealed the binding modes and key interaction sites between NMSP, CSSP, and the MUC2 protein. A Caco-2 monolayer model was established to evaluate polysaccharide uptake and transport under varying concentrations, temperatures, and pH conditions. The results demonstrated that the absorption of both polysaccharides was time- and concentration-dependent, while transport analyses revealed that both NMSP and CSSP could traverse the Caco-2 cells, primarily via endocytic pathways. In terms of apparent permeability (Papp) and transport rate, CSSP exhibited moderate absorption, whereas NMSP was classified as poorly absorbed. Moreover, acidic conditions significantly enhanced the transport rates of both polysaccharides. This study provides critical insights into the absorption and transport characteristics of soybean seed coat polysaccharides, offering a theoretical foundation for further exploration of their bioavailability and physiological functions.
研究领域:
食品科学
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分子生物学
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PubMed
高影响因子
Frontiers in Nutrition
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2022
·
IF 6.59
Qianqian Yao,Linlin Fan,Nan Zheng,Christophe Blecker,Véronique Delcenserie,Huiying Li,Jiaqi Wang
Gut microbiota dysbiosis, together with goblet cells dysfunction has been observed in ulcerative colitis cases. This study aims to evaluate the potential of 2′-fucosyllactose (2′-FL) supplementation in inhibiting intestinal inflammation through regulating gut microbiota, protecting goblet cells, and stimulating mucin secretion. 2′-FL was orally administered to C57BL/6J mice daily (400 mg/kg bw) for 21 days and 5% dextran sulfate sodium (DSS) was used to induce the colitis in the last 7 days. Meanwhile, fecal microbiota transplantation (FMT) was conducted to test the roles of gut microbiota in the remission of colitis by 2′-FL. Gut microbiota alteration was analyzed through 16S ribosomal RNA (16S rRNA) sequencing. Periodic acid-Schiff (PAS), immunofluorescence staining, as well as mucin 2 (MUC2) and NOD-like receptor family pyrin domain containing 6 (NLRP6) messenger RNA (mRNA) expression in colon fragments was performed and detected. The results showed that the DSS + 2′-FL mice were found to have a slower rate of weight loss, lower disease activity index (DAI) scores, and longer colon lengths than the DSS group ( p < 0.05), so in the FMT recipient mice which received fecal microbiota from the DSS + 2′-FL group. In addition, the data revealed that 2′-FL relieved the disorder of DSS-induced gut microbiota, including decreasing the high abundance of mucin-utilizing bacteria in the DSS group, such as Bacteroides, Lachnospiraceae NK4A136, Lachnospiraceae , and Bacteroides vulgatus . PAS and immunofluorescence staining showed that 2′-FL treatment promoted the recovery of goblet cells and enhanced MUC2 and NLRP6 expression, which was also observed in the FM (DSS + 2′-FL) group. Moreover, NLRP6, which has been proved to be a negative regulator for Toll-like receptor 4/myeloid differential protein-8/nuclear factor-kappa B (TLR4/MyD88/NF-κB) pathway, was upregulated by 2′-FL in colon tissue. In conclusion, this study suggests that 2′-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism associates with the recovery of goblet cells number and improves MUC2 secretion through TLR4-related pathway.
研究领域:
免疫学
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微生物学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
Microbiome
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2026
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IF 14.9
Fu Yang,Yin Nuoming,Huang Zehua,Qin Wenfei,Xu Binqiang,Huang Huizhen,Hu Jia,Cui Mengyan,Mei Qixiang,Fan Junjie,Lu Yingying,Jiang Qiaoli,Hu Junjie,Huang Chunlan,Zeng Yue
Background Gut barrier dysfunction is critical in the pathogenesis of acute pancreatitis (AP), yet the underlying mechanisms remain unclear. Mucin 2 (MUC2), the primary component of the intestinal mucus layer, is essential for gut homeostasis and microbial eubiosis. This study aimed to elucidate the protective mechanism of intestinal MUC2 in AP. Results We reported that intestinal MUC2 expression was decreased in AP patients and correlated with disease severity. Intestinal epithelial-specific Muc2 knockout ( Muc2 ΔIEC ) mice demonstrated exacerbated AP in a gut microbiota-dependent manner. Decreased abundance of Lactobacillus and correlated reduced levels of riboflavin were found in Muc2 ΔIEC mice after AP induction. Supplementation with riboflavin effectively ameliorated AP in Muc2 ΔIEC mice, whereas administration of an engineered strain deficient in riboflavin synthesis failed to provide a protective effect. MUC2 deficiency aggravated a macrophage-dominant immune imbalance in the pancreas, which was reversed by riboflavin. In vitro experiments revealed that riboflavin suppresses pro-inflammatory macrophage activation by inhibiting the CD40 signaling pathway. This inhibition preserved mitochondrial function and reversed the histone H3 acetylation at pro-inflammatory gene promoters. Conclusion Our study demonstrates that intestinal MUC2 deficiency is associated with reduced levels of microbiota-derived riboflavin, which could partially suppress pro-inflammatory macrophage activation via the CD40 pathway. Targeting the microbiota-derived riboflavin in AP may help to ameliorate the disease course.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
You Wu,Jiaojiao Li,Wenjiao Ding,Zheng Ruan,Li Zhang
The intestinal barrier is essential for maintaining human intestinal health. The growing number of studies has shown that both puerarin and tryptophan and its metabolites have a beneficial effect on the intestinal barrier. This study aims at the combination of puerarin and tryptophan or its metabolites for improving the intestinal barrier. In our study, 40 female Sprague–Dawley rats were randomly divided into five groups (n = 8) for a 4-week experiment and dextran sodium sulfate was used to induce an intestinal barrier injury in rats. Our results showed that puerarin combined with tryptophan or its metabolites (indole-3-propionic acid, IPA) improved the intestinal barrier by enhancing the mucus layer barrier, which was mainly achieved by increasing the number of goblet cells and promoting the secretion of MUC2. Both TRPM5 and VAMP8 promoted MUC2 secretion in goblet cells through exocytosis, but their mechanisms of action are different. In our study, we found that puerarin and tryptophan showed different effects on TRPM5 and VAMP8, respectively. Puerarin enhances the expression of TRPM5, and tryptophan inhibits the expression of TRPM5; however, puerarin and tryptophan have no significant effect on the expression of VAMP8.
研究领域:
药理学
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胃肠病学
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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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2024
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IF 5.7
Yaqian Li,Hongtao Xu,Liuyang Zhou,Yuwei Zhang,Wenqing Yu,Shubo Li,Jie Gao
In this study, we aimed to explore the protective effects of Bifidobacterium in colitis mice and the potential mechanisms. Results showed that Bifidobacterium breve (B. breve) effectively colonized the intestinal tract and alleviated colitis symptoms by reducing the disease activity index. Moreover, B. breve mitigated intestinal epithelial cell damage, inhibited the pro-inflammatory factors, and upregulated tight junction (TJ)-proteins. Gut microbiota and metabolome analysis found that B. breve boosted bile acid-regulating genera (such as Bifidobacterium and Clostridium sensu stricto 1), which promoted bile acid deconjugation in the intestine. Notably, cholic acid (CA) was closely associated with the expression levels of inflammatory factors and TJ-proteins (p < 0.05). Our in vitro cell experiments further confirmed that CA (20.24 ± 4.53 pg/mL) contributed to the inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression (49.32 ± 5.27 pg/mL) and enhanced the expression of TJ-proteins (Occludin and Claudin-1) and MUC2. This study suggested that B. breve could be a probiotic candidate for use in infant foods.
研究领域:
胃肠病学
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微生物学
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免疫学
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营养学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
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2020
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IF 2.659
Lingzi Yu,Xiaochen Xie,Keyang Jiang,Yi Hong,Zhou Zhou,Yuling Mi,Caiqiao Zhang,Jian Li
The rapid renewal and repair of the intestinal mucosa are based on intestinal stem cells ( ISC ), which are located at the crypt bottom. Paneth cells are an essential component in the crypt, which served as the niche for ISC development. However, in the chicken, how the function of Paneth cells changes during intestinal inflammation is unclear and is the key to understand the mechanism of mucosal repair. In the present study, 36 HyLine White chickens (7 d of age, n = 6) were randomly divided into 1 control and 5 lipopolysaccharide ( LPS ) injection groups. The chickens were injected (i.p.) with PBS in the control group, however, were injected (i.p.) with LPS (10 mg/kg BW) in the LPS injection groups, which would be sampled at 5 time points (1 h postinjection [ hpi ], 2 hpi, 4 hpi, 6 hpi, and 8 hpi). Results showed that tumor necrosis factor-α mRNA transcription in duodenal tissue increased gradually since 1 hpi, peaked at 4 hpi, and then reduced remarkably, indicating that 4 hpi of LPS was the early stage of intestinal inflammation. Meanwhile, the MUC2 expression in duodenal tissue was dramatically reduced since 1 hpi of LPS. The ISC marker, Lgr5 and Bmi1 , in the duodenal crypt were reduced from 1 hpi to 4 hpi and elevated later. Accordingly, the hydroethidine staining showed that the reactive oxygen species level, which drives the differentiation of ISC, in the duodenal crypt reduced obviously at 1 hpi and recovered gradually since 4 hpi. The analysis of Paneth cells showed that many swollen mitochondria appeared in Paneth cells at 4 hpi of LPS. Meanwhile, the Lysozyme transcription in the duodenal crypt was substantially decreased since 1 hpi of LPS. However, the Wnt3a and Dll1 in duodenal crypt decreased at 1 hpi of LPS, then increased gradually. In conclusion, Paneth cells were impaired at the early stage of intestinal inflammation, then recovered rapidly. Thus, the ISC activity was reduced at first and recovery soon.
研究领域:
免疫学
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胃肠病学
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动物科学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Haiyan Xue,Yalin Tan,Baoyuan He,Yan Zhou,Bowei Ding,Yawen Wu,Jun Ma,JiaYi Wang,Wenmin Dong
Phlorizin (PZ), a naturally occurring flavonoid glycoside in Malus exhibits dual therapeutic potential as an antioxidant and antidiabetic agent, however its clinical translation is constrained by poor aqueous solubility (<0.1 mg/mL) and suboptimal bioavailability. To address these limitations, this study examined supramolecular complexation with β-lactoglobulin (β-LG), a whey protein carrier capable of hydrophobic nutrient transport and known for its immunomodulatory properties. Furthermore, the molecular binding mechanism, gastrointestinal stability, and synergistic effects of the PZ–β-LG complex on intestinal mucosal secretion were systematically characterized by integrating computational simulations, spectroscopic validation, and in vitro functional assays. Molecular dynamics simulations revealed that the PZ preferential bound within the calyx domain of β-LG (ΔG = −8.3 kcal/mol) through hydrophobic interactions and hydrogen bonding, as evidenced by emerging UV–Visible absorption peaks between 300 and 350 nm and intrinsic fluorescence spectroscopy. Simulated gastrointestinal digestion coupled with Liquid Chromatography–Tandem Mass Spectrometry(LC-MS/MS) peptidomics demonstrated a significant reduction in β-LG antigenicity reduction(52.1% vs. free β-LG; P < 0.01), which might be attributed to the enhanced gastrointestinal hydrolysis efficiency and the masking of immunoreactive epitopes Notably, 2 digestion-resistant peptides (VAGTWY-42 and LDAQSAPLR-89) persisted across all groups, suggesting potential allergenicity hotspots that may require further investigation. Cellular assessments using intestinal epithelium LS174T cells revealed that β-LG complexation reduced PZ associated cytotoxicity by 62% ( P < 0.05) while synergistically upregulating the expression of mucin-2 (MUC2) at both transcriptional (2.5-fold increase) and secretory levels (2.1-fold elevation vs. control). Overall, these findings indicate that hydrophobic-driven complexation PZ with β-LG not only enhances the bioavailability of polyphenol but also decreases the antigenicity of protein carrier in intestine cells.
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2023
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IF 8.9
Mengxing Cui,Qianmei He,Ziwei Wang,Yongjiang Yu,Huan Gao,Ziqi Liu,Honghao Peng,Han Wang,Xue Zhang,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Qing Wang
Micro/nano-plastics (MPs/NPs) are a newly discovered environmental pollutant that can be ingested by humans through food and drinking water. In this study we evaluated the impact of MPs/NPs on the intestinal barrier and its mechanism. Doses of MPs/NPs were used to treat Caco-2/HT29-MTX in-vitro model and in-vivo model. In in-vitro model, 20 nm polystyrene nanoplastics (PS-NPs) had higher cytotoxicity than larger particles (200 nm and 2000 nm), and led to the increase of the permeability along with the decreased expression of tight junction proteins. Intriguingly, 20 nm PS-NPs elevated the expression of MUC2 simultaneously. Further studies revealed that PS-NPs increased the expression of HO1 through ROS generation, and then activated p38 to elevate IL-10 secretion in Caco-2 cell. The IL-10 secreted by Caco-2 cell promoted the expression of MUC2 in HT29-MTX cell through STAT1/3. Elevated MUC2 expression alleviates the cytotoxicity of PS-NPs. Besides, increased intestinal permeability and up-regulation of MUC2 through Ho1/p38/IL-10 pathway was also observed in 20 nm PS-NPs treated mouse model. In conclusion, PS-NPs can induce the intestinal toxicity and result in the increased adaptive expression of MUC2 to resist this adverse effect. People with inadequate mucin expression need to pay more attention to the toxicity of PS-NPs. This study provided a valuable insight for clarifying the mechanism and potential risk of intestinal toxicity induced by nanoplastics.
研究领域:
环境科学
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毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2020
·Vol. 64
·期 8
·1901251
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IF 5.309
Lingjun Tong,Haining Hao,Xinyi Zhang,Zhe Zhang,Youyou Lv,Lanwei Zhang,Huaxi Yi
Scope Milk-derived extracellular vesicles (mEVs) as nanoparticles are being developed as novel drug vehicles due to their pivotal role in cell–cell communication. As an important bioactive component in milk, little is known about their effect on the gut microbiota and intestinal immunity. Therefore, the effects of mEVs on gut microbiota and intestinal immunity in mice are investigated. Methods and results First, a new method to obtain high-yield mEVs is developed. Afterward, the colonic contents from C57BL/6 mice fed different doses of mEVs (8 weeks) are collected and the microbial composition via 16S rRNA gene sequencing is analyzed. It is found that mEVs could alter the gut microbiota composition and modulate their metabolites—short-chain fatty acids (SCFAs). Furthermore, the effects of mEVs on intestinal immunity are evaluated. It is observed that the expression levels of Muc2, RegIIIγ, Myd88, GATA4 genes, and IgA, sIgA are increased in the intestine, which are significant for the integrity of the mucus layer. Conclusion These findings reveal that the genes with critical importance for intestinal barrier function and immune regulation are modified in mice by oral administration mEVs, which also result in the changes of the relative composition of gut microbiome and SCFAs.
研究领域:
药理学
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微生物学
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免疫学
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营养科学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2026
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IF 4.5
Dan Shao,Longqing Hu,Wei Guo,Jinglong Chen,Xuming Guo,Hong Yao
This study aimed to investigate the protective effect and mechanism of dietary dimethylglycine (DMG) on jejunal injury in yellow-feathered broilers subjected to cyclic heat stress (HS). A total of 180 35-day-old male yellow-feathered broilers were randomly allocated into 3 groups: the thermoneutral condition with basal diet group (CON), the cycle heat stress with basal diet group (HS, 32-35°C), and the cycle heat stress with 0.1% DMG in basal diet group (HS_DMG, 32-35°C). The experiment included a 7-day heating period followed by a 14-day cyclic heat stress period. Growth performance, rectal temperature, jejunal morphology and ultrastructure, inflammatory cytokine levels, and protein expression related to the TLR4/NF-κB pathway and MUC2 were evaluated. Additionally, primary chicken jejunal epithelial cells were isolated and exposed to heat stress with or without DMG pretreatment to validate in vivo findings. Results showed that heat stress significantly increased rectal temperature ( P < 0.05), had a tendency to reduce body weight (BW, P = 0.058) and average daily gain (ADG, P = 0.050), and increase the feed-to-gain ratio (F/G, P = 0.053). Histologically, HS caused epithelial shedding, reduced villus height and villus height/crypt depth, and induced microvilli damage and mitochondrial swelling, all of which were attenuated by DMG supplementation. Heat stress also elevated jejunal mucosa levels of IL-6, IL-8, IL-1 β , and TNF- α ( P < 0.05), while DMG reduced IL-6, IL-8, and TNF- α ( P < 0.05). Immunohistochemistry and western blotting revealed that HS decreased MUC2 expression and increased TLR4 and p-NF-κB-p65 protein levels ( P < 0.05), whereas DMG reversed these changes ( P < 0.05). In vitro, DMG pretreatment alleviated HS-induced reduction in inflammatory cytokine release, and alterations in TLR4, NF-κB, and MUC2 protein expression. In conclusion, dietary DMG supplementation alleviates cyclic heat stress-induced jejunal injury in yellow-feathered broilers by suppressing the TLR4/NF-κB signaling pathway and restoring MUC2 expression.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 9
·3385
·
IF 4.556
Xin Meng,Jinrui Zhang,Hao Wu,Dahai Yu,Xuexun Fang
Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed inEscherichia coliprokaryote cell system, hereinafter termed Amuc_1434*), derived fromAkkermansia muciniphila, can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived fromAkkermansia muciniphilasuppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.Keywords:Amuc_1434*;colorectal cancer cells;proliferation;apoptosis;TRAIL
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2024
·
IF 4.2
Haoming Luo,Miao Guo,Mingxing Li,Yueshui Zhao,Jing Shen,Fukuan Du,Yu Chen,Shuai Deng,Yuhong Sun,Li Gu,Wanping Li,Xiaobing Li,Meijuan Chen,Zhangang Xiao,Shengpeng Wang,Xu Wu
Introduction Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy.
研究领域:
药理学
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胃肠病学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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