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Biomolecules · 2019 ·Vol. 9 ·期 9 ·486 · IF 4.694

Succinate Modulates Intestinal Barrier Function and Inflammation Response in Pigs

Xuan Li,Mingyu Mao,Yanan Zhang,Kaifan Yu,Weiyun Zhu

Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle in all aerobic organisms, and is also a vital microbial metabolite in the gut. Although succinate is known to regulate intestinal metabolism and immune function, its role in the protection of the intestinal epithelial barrier function and inflammation is poorly characterized. In this study, we evaluated the effects of succinate on intestinal epithelial barrier function and inflammation in pigs. Twenty-four growing pigs were distributed into three groups (n= 8) and received either a basal diet (control group) or the same diet supplemented with 0.1% succinate or 1% succinate. The diet supplemented with 1% succinate led to alterations in the intestinal morphology. We confirmed in vitro that 5 mM succinate treatment modulated intestinal epithelial permeability by increased transepithelial electrical resistance (TEER) in intestinal porcine epithelial cell (IPEC)-J2 cells. Furthermore, succinate treatment increased the abundance of tight junction proteins claudin-1, zona occluden (ZO)-1, and ZO-2 in the jejunum in vivo and in vitro. In addition, dietary succinate supplementation promoted the expression of inflammatory cytokines interleukin (IL)-25, IL-10, IL-8, and IL-18 in the jejunum. Taken together, these data identify a novel role of succinate in the modulation of intestinal epithelial barrier function, which may be a nutritional target to improve gut health in animals.Keywords:succinate;intestinal epithelial barrier;intestinal inflammation;pigs

CAS / MDL: 150-90-3
研究领域: 营养学 · 免疫学 · 动物科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Chemistry-X · 2024 · IF 6.5

Encapsulation of zingerone by self-assembling peptides derived from fish viscera: Characterization, interaction and effects on colon epithelial cells

Sirong Huang,Xintong Yao,Boya Cao,Na Zhang,Olugbenga P. Soladoye,Yuhao Zhang,Yu Fu

The purpose of the present work was to encapsulate zingerone (a bioactive compound from ginger) by self-assembling peptides derived from fish viscera. The encapsulation conditions were investigated and the structure of fish peptides-zingerone complex was characterized. The interaction between zingerone and fish peptides was investigated using fluorescence spectroscopy. Further research was performed on the in vitro release of zingerone and fish peptide-zingerone as well as their antiproliferative effects on colon epithelial Caco-2 cells. The results demonstrated that zingerone can be successfully encapsulated by self-assembling peptides derived from fish viscera with high encapsulation efficiency and loading capacity. Furthermore, transmission electron microscope and confocal laser scanning microscope observations revealed the successful encapsulation of zingerone by fish viscera peptides. In addition, in vitro release and antiproliferative activity against Caco-2 cells can be significantly increased by encapsulating zingerone via peptide self-assembly. The current study advances knowledge of encapsulation of bioactive compounds through peptide self-assembly.

CAS / MDL: 122-48-5 643-79-8
研究领域: 食品科学 · 生物化学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FISH PHYSIOLOGY AND BIOCHEMISTRY · 2019 ·Vol. 45 ·期 2 ·539-549 · IF 1.729

Arginine affects growth and integrity of grass carp enterocytes by regulating TOR signaling pathway and tight junction proteins

Chen Jiaojiao,Zhang Dianfu,Tan Qingsong,Liu Mengmei,Hu Pengcheng

Dietary arginine (Arg) could improve the intestinal structure and absorption of grass carp ( Ctenopharyngodon idellus ); however, the mechanism of Arg on intestinal morphology improvement was unclear. The present study aimed to explain the possible mechanism of the positive effect of Arg on intestinal epithelial cells of grass carp. An in vitro study was conducted through a primary culture model to assess the growth, cell viability, mRNA expressions of TOR signal pathway, and tight junction proteins of enterocytes after culture in the medium with 6 levels of Arg (0, 0.1, 0.2, 0.5, 1.0, and 2.0 mmol/L). The results showed that 0.5 mmol/L Arg improved the cell number and decreased the lactate dehydrogenase and creatine kinase activities in culture medium ( P  < 0.05). The alkaline phosphatase activity in cell lysis buffer was depressed by 1 and 2 mmol/L Arg ( P  < 0.05). The nitric oxide (NO) content showed an increasing trend with the Arg content ( P  < 0.05), whereas the NO synthase activity showed an opposite trend to NO. TOR expression was higher in 0.2 and 0.5 mmol/L groups, whereas S6K1 expression in 1.0 mmol/L and 2.0 mmol/L groups were lower ( P  < 0.05). The mRNA expressions of occludin, claudin 3, and claudin c in 0.5 mmol/L group were the highest, while ZO-1 and claudin b expressions were higher in 0.2 and 0.5 mmol/L groups ( P  < 0.05). This study indicated that Arg enhanced the growth and integrity of intestinal epithelial cells of grass carp through upregulation of mRNA expression of TOR signal pathway and tight junction proteins at an optimal Arg content of 0.2–0.5 mmol/L.

研究领域: 水产养殖 · 分子生物学 · 营养学
✓ 已验证 DOI PubMed 高影响因子
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FISH & SHELLFISH IMMUNOLOGY · 2022 · IF 4.622

Melatonin alleviates lead-induced intestinal epithelial cell pyroptosis in the common carps (Cyprinus carpio) via miR-17-5p/TXNIP axis

Zhiying Miao,Zhiruo Miao,Xiaohua Teng,Shiwen Xu

Lead (Pb) has been concerned as one of the most severe hazardous contaminants, because it can cause pyroptosis in multiple tissues of mammals and birds. Melatonin (Mel) has attracted much interest for its role in governing intestinal injury via microRNAs (miRNAs). To explore the effect of Mel on Pb exposure-induced intestinal epithelial cell pyroptosis in common carps by regulating miR-17-5p/TXNIP axis, the Pb exposure and Pb-Mel treated models were constructed in vivo . The results elucidated that the suppressed expression of miR-17-5p and intensified level of TXNIP were primarily detected in Pb-exposed gut tissues, and both abolished with Mel addition, along with downregulated Pb-mediated elevated expression of NLRP3, CASP1, IL1β and GSDMD. Additionally, the targeting relationship between miR-17-5p and TXNIP were demonstrated by dual-luciferase reporter assay, and on this basis, miR-17-5p NC, mimic and inhibitor cell models were established. Thereby, Thereby, the expression of TXNIP in the miR-17-5p mimic groups was significant lower in the Pb-exposure but still elevated than the Control group, and the expression of NLRP3 and NLRP3-dependent pyrotposis-related genes performed consistent alterations. Noticeably, the expression of TXNIP suppressed with Mel addition even in the miR-17-5p inhibitor cell model, resulting in the inactivation of NLRP3 inflammasome-dependent pyroptosis. Overall, we draw the conclusion as Mel attenuates Pb-induced intestinal epithelial cell pyroptosis via miR-17-5p/TXNIP axis. The present study provides a novel perspective for toxicological mechanism of Pb, and new insights for the detoxification mechanism of Mel.

研究领域: 毒理学 · 分子生物学 · 水生生物学 · 环境科学
✓ 已验证 DOI PubMed 高影响因子
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CARBOHYDRATE RESEARCH · 2025 · IF 2.5

Chemical structure and anti-inflammatory effects on intestinal epithelial cells of a novel mannogalactan purified from Typhonium giganteum Engl.

Hongchen Luo,Zhengyang Lai,Lexue Shi,Yulong Hu,Can Jin,Kan Ding

Inflammatory bowel disease (IBD) remains a pressing global health challenge due to its complex pathogenesis and limited treatment efficacy. Mannogalactans, abundant in certain algae and edible fungi, are recognized for their diverse biological functions, particularly their potent anti-inflammatory effects. Motivated by these findings, we hypothesized that Typhonium giganteum Engl. may contain structurally analogous mannogalactans with therapeutic potential against enteritis. To investigate, we isolated and purified a homogeneous polysaccharide, BFZ213, using hot water extraction, ethanol precipitation, and chromatographic techniques. Comprehensive structural analysis, employing methylation analysis, partial acid hydrolysis, 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization, infrared spectroscopy, HPLC, GC-MS, and NMR spectroscopy, identified BFZ213 as a novel mannogalactan (160 kDa). The backbone comprises 1, 3-linked mannose, 1, 2, 3-linked mannose, 1, 4-linked glucuronic acid, and 1, 2, 4, 6-linked galactose, with branching at the C-4 and C-6 positions of 1, 2, 4, 6-linked galactose, including 1, 4-linked galactose, 1, 6-linked galactose, terminal galactose, and arabinose. Bioactivity studies demonstrated that BFZ213 significantly suppressed TNF-α and IL-1β secretion in LPS-stimulated NCM460 cells and attenuated MAPK and NF-κB signaling by inhibiting the phosphorylation of p38, JNK, p65, and IκBα. These results highlight BFZ213 as a promising lead compound for IBD therapy, underscoring the therapeutic relevance of mannogalactans.

CAS / MDL: 298-93-1
研究领域: 生物化学 · 药理学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Science & Nutrition · 2025 ·Vol. 13 ·期 4 ·e70113 · IF 3.8

Thymoquinone Ameliorates Gut Epithelial Injury by Suppressing the JNK Signaling Pathway Based on Its Anti-Oxidant Property

Kaitong Jia,Lei Wu,Ziru Li,Tian Wei,Tingting Fan,Guiran Xiao

Ulcerative colitis is one of the most common sorts of inflammatory bowel disease. This study investigates the protective effects of thymoquinone against sodium dodecyl sulfate (SDS)-induced intestinal damage and elucidates the underlying mechanisms using the Drosophila melanogaster model of ulcerative colitis. We found that Drosophila fed thymoquinone from larval to adult stages were resistant to SDS injury in adulthood. Thymoquinone pretreatment significantly restored the abnormal behaviors and intestinal morphological defects in Drosophila exposed to SDS. Moreover, thymoquinone protected the intestinal barrier function by inhibiting the overactivated c-Jun N-terminal kinase (JNK) pathway in the intestine induced by SDS. Further studies indicated that thymoquinone inhibits the JNK pathway by reducing intestinal reactive oxygen species (ROS) levels. This research provides novel pathological and mechanistic insights into the potential application of thymoquinone in developing functional foods or natural medicines, highlighting its significance in treating ulcerative colitis.

CAS / MDL: 490-91-5
研究领域: 医学 · 生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2023 · IF 5.6

ROS-activated MAPK/ERK pathway regulates crosstalk between Nrf2 and Hif-1α to promote IL-17D expression protecting the intestinal epithelial barrier under hyperoxia

Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu

Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.

CAS / MDL: 7646-79-9
研究领域: 分子生物学 · 细胞生物学 · 儿科 · 肠道生理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY · 2021 ·Vol. 21 ·期 9 ·4586-4595 · IF 0

Effect of Short-Term Exposure to Titanium Dioxide Nanoparticles on Intestinal Absorption of Glucose by Ex Vivo Everted Rat Gut Sac Model

Wang Yun,Chen Zhangjian,Chen Shi,Zhuo Lin,Zhao Lin,Jia Guang

Titanium dioxide nanoparticles (TiO2 NPs) as food additives were widely found in various foodrelated products, especially in high-sugar foods. The daily intake of TiO2 NPs in the diet may therefore expose the small intestine to TiO2 NPs and affect its physiological functions, including the absorption of nutrients. It is speculated that TiO2 may cause serious health hazards by increasing sugar uptake. To explore this possibility, transport of glucose from small intestine was studied using an everted gut sac model prepared from small intestine of young healthy male SD rats. The translocation of TiO2 NPs and the morphological changes of small intestine were also observed after exposure of intestinal lumen to TiO2 NPs for 2 h. The results showed that TiO2 NPs can enter into enterocyte but hardly cross the intestinal epithelium. No change on microstructure of gut epithelia and expression of glucose transporter was found, and there is no obvious impact on intestinal absorption and metabolism of glucose. These results suggest that short-term exposure to TiO2 NPs has little influence on intestinal absorption of glucose. More attention should be paid to the chronic effect of dietary consumption of TiO2 NPs on nutrient absorption.

研究领域: 纳米技术 · 营养科学 · 毒理学
✓ 已验证 DOI PubMed
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PeerJ · 2022 · IF 3.061

Microfluidics-assisted electrospinning of aligned nanofibers for modeling intestine barriers

Wentao Su,Miao Zhang,Wenbo Wei,Haitao Wang,Wei Zhang,Zhongyu Li,Mingqian Tan,Zongzheng Chen

During electrospinning, the fibers deposited on the collector are usually randomly oriented in a disordered form. Researchers hope to generate periodic structures to expand the application of electrospinning, including improving the sensing properties of electronic and photonic devices, improving the mechanical properties of solid polymer composites and directional growth of human tissues. Here, we propose a technique to control the preparation of aligned foodborne nanofibers by placing dielectric polymers on microfluidic devices, which does not require the use of metal collectors. This study was conducted by introduced PEDOT:PSS polymer as a ground collector to prepare aligned foodborne nanofibers directly on the microfluidic platform. The fluidity of the electrolytic polymer collector makes it possible to shape the grounding collector according to the shape of the microcavity, thus forming a space adjustable nanofiber membrane with a controllable body. The simplicity of dismantling the collector also enables it extremely simple to obtain a complete electrospun fiber membrane without any additional steps. In addition, nanofibers can be easily stacked into a multi-layer structure with controllable hierarchical structures. The Caco-2 cells that grow on the device formed a compact intestinal epithelial layer that continuously expresses the tightly bound protein ZO-1. This intestinal barrier, which selectively filters small molecules, has a higher level of TEER, reproducing intestinal filtration functions similar to those of in vivo models. This method provides new opportunities for the design and manufacture of various tissue scaffolds, photonic and electronic sensors.

研究领域: 材料科学 · 生物医学工程 · 组织工程 · 纳米技术
✓ 已验证 DOI 高影响因子
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PHYTOMEDICINE · 2023 · IF 7.9

Kaempferol ameliorated alcoholic liver disease through inhibiting hepatic bile acid synthesis by targeting intestinal FXR-FGF15 signaling

Li Xiao,Guangfu Xu,Silong Chen,Yumin He,Fan Peng,Chengfu Yuan

Background Alcoholic liver disease (ALD) is characterized by the disturbance of bile acids homeostasis, which further deteriorates ALD. Bile acid metabolism and its related signal molecules have become new therapeutic targets for alcoholic liver disease. This study aimed to investigate the impact of kaempferol (KAE) on ALD and elucidate its underlying mechanisms. Methods C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. KAE was administered as an interventional drug to chronic alcohol-fed mice for four weeks to assess its effects on liver damage and bile acid metabolism. And Z-Guggulsterone (Z-Gu), a global FXR inhibitor, was used to investigate the impact of intestinal FXR-FGF15 signal in ALD mice. Additionally, intestinal epithelial cells were exposed to alcohol or specific bile acid to induce the damage of FXR activity in vitro. The dual luciferase activity assay was employed to ascertain the interplay between KAE and FXR activity. Results The results indicated that KAE treatment exhibited a significant hepatoprotective effect against chronic alcohol-fed mice. Accompanied by the intestinal FXR activation, the administration of KAE suppressed hepatic bile acid synthesis and promoted intestinal bile acid excretion in chronic ALD mice. And the notable alterations in total bile acid levels and composition were observed in mice after chronic alcohol feeding, which were reversed by KAE supplementation. And more, the protective effects of KAE on ALD mice were deprived by the inhibition of intestinal FXR activation. In vitro experiments demonstrated that KAE effectively activated FXR-FGF15 signaling, mitigated the damage to FXR activity in intestinal epithelial cells caused by alcohol or specific bile acids. Additionally, luciferase activity assays revealed that KAE directly promoted FXR expression, thereby enhancing FXR activity. Conclusion KAE treatment inhibited hepatic bile acids synthesis, maintained bile acids homeostasis in ALD mice by directly activating intestinal FXR-FGF15 signaling, which effectively alleviated liver injury induced by chronic alcohol consumption.

CAS / MDL: 127-08-2
研究领域: 药理学 · 肝病学 · 分子生物学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR NUTRITION & FOOD RESEARCH · 2022 ·Vol. 66 ·期 24 ·2200455 · IF 6.575

Oleuropein Prevents OVA-Induced Food Allergy in Mice by Enhancing the Intestinal Epithelial Barrier and Remodeling the Intestinal Flora

Yuanjie Guo,Yu Ma,Liyuan Ma,Zixin Guo,Yingliang Xiao,Yunjun Liu,Jie Li,Shengnan Wang,Yixiang Liu

Scope This study assesses whether oleuropein prevents ovalbumin (OVA)-induced food allergy (FA) and investigates the underlying mechanisms. Methods and results A Balb/c FA mouse model is established and maintained for 7 weeks. The subjects are administered OVA by oral gavage to induce FA and supplemented with different oleuropein doses (1.00–20.00 mg kg −1 per day) to evaluate its preventative efficacy. The results indicate that oleuropein effectively alleviates OVA-induced allergy symptoms and promotes temperature elevation in sensitized mice. The secretion of serology-specific OVA-immunoglobulin (Ig)E, OVA-IgG, and histamine is inhibited in the sensitized mice. Oleuropein dramatically upregulates the expression of intestinal tight junction (TJ) proteins, regenerating gene (Reg) IIIγ, and interleukin (IL)-22, enhancing the physical and biochemical barrier function of the intestinal epithelium. Additionally, oleuropein improves the immune homeostasis of the intestinal epithelium by affecting the function of mucosal mast cells and regulatory T (Treg) cells. The disordered intestinal flora of the sensitized mice also improves after oleuropein administration. Conclusions These findings suggest that oleuropein prevents FA by enhancing intestinal epithelial barrier function and improving immune homeostasis and intestinal flora in sensitized mice. Therefore, diets rich in oleuropein should be recommended for people with FA.

CAS / MDL: 9006-59-1
研究领域: 免疫学 · 胃肠病学 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Bifidobacterium breve Protects the Intestinal Epithelium and Mitigates Inflammation in Colitis via Regulating the Gut Microbiota–Cholic Acid Pathway

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.

CAS / MDL: 9011-18-1
研究领域: 胃肠病学 · 微生物学 · 免疫学 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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