Oncology Letters
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2018
·Vol. 17
·期 1
·652-659
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IF 1.664
Hongchao Han,Jie Xu,Weiwei Ji,Lisheng Wang,Aikun Wang
Transmembrane protein with epidermal growth factor (EGF)‑like and two follistatin motifs 2 (TMEFF2) is downregulated in human gastric cancer, and its levels are associated with tumor aggressiveness. Herein, a positive correlation was identified between serum vitamin C levels (µg/ml) and mRNA levels of TMEFF2 in gastric cancer tissue. TMEFF2 silencing promotes cell proliferation in GES‑1 normal human gastric epithelial cells and AGS human gastric adenocarcinoma cells. Notably, vitamin C and AG490 exerted antiproliferative effects on the two cell lines. The present study demonstrated that small interfering (si)‑RNA‑TMEFF2 exerts pro‑proliferative effects on GES‑1 and AGS cells. The results revealed that vitamin C significantly inhibited the growth of GES‑1 and AGS cells by reducing cell viability, decreasing the expression of proliferating cell nuclear antigen (PCNA), and blocking the STAT3 pathway. Moreover, siRNA‑TMEFF2‑induced enhanced cell viability and PCNA expression were significantly reversed by additional vitamin C treatment; notably, markedly enhanced TMEFF2 expression was observed. Upregulated TMEFF2 expression was observed in association with the antiproliferative effect of AG490. In conclusion, serum vitamin C content (µg/ml) was positively correlated with the mRNA levels of TMEFF2 in gastric cancer tissue. Exploring novel drugs that target TMEFF2 is a potential therapeutic strategy for blocking human GC.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2022
·Vol. 87
·期 6
·2417-2426
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IF 3.693
Erdong Yuan,Miao Zhou,Shiying Nie,Jiaoyan Ren
The interaction between zinc oxide nanoparticles (ZnO NPs) and whey protein (WP) was studied. The gastric epithelial cell line (GES-1) was used to evaluate the toxicity intensity of ZnO NPs. The interaction mechanism of ZnO NPs and WP was studied by spectroscopic techniques. The results showed that the inhibitory effect of ZnO NPs on cells activity could be reduced when added to ZnO NPs at a concentration of 50 µg/ml. The fluorescence quenching mechanism of ZnO NPs on WP is a combination of dynamic and static quenching. The interaction force between ZnO NPs and WP can be considered as H-bond and VdW force, and they have two binding sites. The interaction between WP and ZnO NPs leads to the loosening of the structural skeleton of WP and the extension of peptide chain, which exposes the tyrosine (Tyr) and tryptophan (Trp) hydrophobic groups in the hydrophobic region of protein molecules and reduces the hydrophobicity of the microenvironment. The ZnO NPs might form a complex with WP through H-bond, hydrophobic interactions, and so on, leading to peptide chain rearrangement, and finally causing changes in the secondary structure of α-helix. 1.1 Practical Application This study provides a theoretical basis for future research on the interaction between food ingredients and nanomaterials, the evaluation of toxicity of nanomaterials and the application scope of nanomaterials in food field.
研究领域:
食品科学
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分子生物学
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毒理学
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PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 7
·e0328000
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IF 2.6
Shuaijun Peng,Ruiqin Sun,Hui Liu,Baoying Wang,Yucheng Li
Gastric mucosal injury can lead to significant gastrointestinal disorders, including inflammation, ulcers, and intestinal metaplasia in severe cases. Although bile acids are known contributors to mucosal damage due to their acidity, the role of chenodeoxycholic acid (CDCA), a primary bile acid, in gastric mucosal injury remains unclear. This study investigates the role of CDCA in inducing gastric mucosal injury and its underlying mechanisms, with a focus on apoptosis and FXR activation, to identify potential therapeutic targets. Mice were administered varying doses of CDCA to evaluate changes in body weight, food intake, and gastric mucosal pathology using hematoxylin-eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Expression levels of apoptosis-related genes (BAX, BCL-2) and the intestinal metaplasia marker gene (CDX2) were analyzed via RT-PCR and Western blotting (WB). GES-1 cells were treated with different CDCA concentrations to assess cell viability via the CCK-8 assay. Apoptosis rates were measured using flow cytometry, and FXR inhibitors were applied to examine their impact on CDCA-induced effects. CDCA administration in mice resulted in weight loss, reduced food and water intake, gastric epithelial shedding, and intestinal metaplasia. CDCA exposure upregulated Bax and CDX2 expression, while reducing BCL-2 levels. In vitro, CDCA inhibited GES-1 cell viability and increased apoptosis rates, effects that were reversed by FXR inhibition. CDCA induces gastric mucosal injury through apoptosis and FXR activation. These findings provide insights into the mechanisms of bile acid-mediated mucosal damage and highlight FXR as a potential therapeutic target for gastric mucosal disorders.
研究领域:
胃肠病学
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细胞生物学
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分子生物学
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药理学
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病理学
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2024
·
IF 5.3
Xinrui Meng,Jingjing Liu,Jia Kang,Menghan Wang,Zhanghui Guan,Dong Tian,Xinping Chen
Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1.
研究领域:
胃肠病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
TISSUE & CELL
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2024
·
IF 2.7
Lei Zhu,Qingxin Cai,Gang Li,Xiaoming Zou
Objective Gastric precancerous lesions (GPL), characterized by intestinal metaplasia and dysplasia, marks a pivotal juncture in the transformation from gastritis to gastric cancer. Research on GPL could offer fresh perspectives on preventing cancer occurrence. Methods This study employed 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to establish GPL rat models and knocked BRD4 down in vivo to assess its impact on the lesions and macrophage morphology. Following that, the impacts of BRD4 knockdown on the malignant phenotypes of human gastric epithelial GES-1 cells were determined. Moreover, conditioned medium from macrophage was gathered and used for GES-1 cell culture. The involvement of macrophage polarization in the BRD4 regulatory mechanism in GES-1 cells was assessed. Results This study elucidated that MNNG induced an increase level of BRD4 in the rat models. BRD4 knockdown reduced lesions based on pathological sections and immunohistochemistry to detect proliferative antigens. Western blotting and immunofluorescence showed that BRD4 knockdown suppressed epithelial-mesenchymal transition and macrophage M2 polarization. In in vitro experiments, BRD4 knockdown inhibited the malignant phenotype of GES-1 cells and the differentiation of THP-1 cells into M2 macrophages, respectively. The conditioned medium from M2 macrophages with BRD4 knockdown was co-incubated with GES-1 cells, which attenuated the malignant phenotypes compared with the medium from M2 macrophages. Conclusion: Through in vivo and in vitro experiments, BRD4 upregulation was found to already occur during GPL, affecting macrophage polarization and epithelial cell cancerization. This finding provides an experimental basis for strategies targeting BRD4 inhibition at this critical stage.
研究领域:
肿瘤学
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免疫学
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分子生物学
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PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Qichao Hu,Yuan Chen,Wenwen Zhang,Yubing Li,Xinyu Deng,Lisheng Chen,Zongyuan Zhou,Xiao Ma,Jinhao Zeng,Yanling Zhao
Background Acute gastric injury, a common and recurring global digestive disorder, significantly impairs patient quality of life and overall health. Dehydroevodiamine (DHE), a bioactive natural product derived from Tetradium ruticarpum ( A. Juss. ) Hartley, shows potential therapeutic effects on acute gastric injury. This study investigates the underlying mechanisms of DHE's alleviating effects on acute gastric injury. Methods The gastric mucosal protective effect of DHE was confirmed through in vivo and in vitro acute gastric injury models. Biotin pulldown MS and molecular dynamics simulations identified DHE's target. CETSA and SPR assays validated DHE's affinity for IKKβ. Protein site mutation validation and MST pinpointed the direct binding sites of DHE on IKKβ. Additionally, the potential mechanism by which DHE ameliorates acute gastric injury was elucidated using WB, IHC, and IF methods, and further confirmed by rescue experiments. Results DHE effectively ameliorated IDO-induced gastric injury in GES-1 cells and rat gastric mucosa, both in vitro and in vivo . Biotin pulldown MS identified IKKβ as the target of DHE in alleviating gastric injury. CETSA and SPR assays confirmed DHE's direct binding to IKKβ. Molecular dynamics simulations, protein mutation experiments, and MST results pinpointed GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket as the binding sites of DHE on IKKβ. Notably, DHE was found to competitively bind to IKKβ with ATP. Mechanistically, DHE attenuated IDO-induced gastric injury by inhibiting the IKKβ-p65/NLRP3 signaling pathway. Importantly, exogenous activation of IKKβ reversed the therapeutic effect of DHE, indicating that DHE's efficacy depends on IKKβ. Conclusion DHE attenuated IDO-induced gastric injury by inhibiting the IKKβ-p65/NLRP3 signaling pathway. Notably, DHE is a novel ATP-competitive IKKβ inhibitor that prevents phosphorylation by targeting GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket. This study reveals new targets of action for DHE, providing a new molecular basis for using DHE in treating inflammation-related diseases.
研究领域:
药理学
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胃肠病学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Junjie Qiu,Xiao Xu,Jingyan Guo,Zhenyu Wang,Jinjin Wu,Huiqin Ding,Yuchen Xu,Yili Wu,Qianyi Ying,Jiawei Qiu,Suxiang Wu,Senlin Shi
We optimized the extraction process of Bletilla striata polysaccharides using orthogonal design, Box-Behnken design (BBD), and genetic algorithm-back propagation (GA-BP), then compared and evaluated them to confirm that the combination of BBD and GA-BP neural networks was capable of increasing polysaccharide yields and antioxidant activity. The optimal extraction parameters were as follows: liquid-to-solid ratio of 15 mL/g, extraction power of 450 W, and extraction time of 34 min. Under these conditions, the polysaccharide yield and antioxidant activity were 8.29 ± 0.50 % and 26.20 ± 0.28 (mM FE/mg). Subsequently, the polysaccharide was purified to obtain purified Bletilla striata polysaccharides 1 (pBSP1) with a Mw of 255.172 kDa. Scanning electron microscope (SEM), ultraviolet-visible detector (UV), fourier transform infrared spectrometer (FTIR), high performance liquid chromatography (HPLC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and periodate oxidation were used to analyze the structure of pBSP1. The results showed pBSP1 had a smooth surface and a rough interior, with a composition of α-D conformation glucose (18.23 %) and β-D conformation mannose (53.77 %), and an amorphous crystal structure. According to the results of thermogravimetric and rheological tests, pBSP1 exhibits good thermal stability and viscoelastic behavior. Furthermore, pBSP1 protected lipopolysaccharide (LPS)-induced GES − 1 and Caco2 cells, the results showed pBSP1(400 μg/mL) lowered TEER synthesis in Caco2 cells as well as apoptosis and reactive oxygen species (ROS) production in both cells, indicating that pBSP1 may have an intestine protective effect.
研究领域:
药理学
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生物化学
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食品科学
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生物技术
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PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2021
·Vol. 18
·期 3
·e2000864
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IF 2.408
Yijia Qi,Weiming Ren,Haixia Zhang,Gang Chen,Weiyi Huang,Xuexia Li,Jie He,Weichun Zhao
Veronicastrum axillare polysaccharides (VAP) were isolated by cellulase-assisted digestion. The optimum conditions (2 % cellulase, 47 °C for 2.5 h, then, 95 °C for 2.5 h, pH 4.1, solid/liquid ratio 1 : 7.6) were identified by a combination of single factor optimization and response surface DOE (design of experiment) methods, and achieved a yield of 4.7 %. Treatment with 1 % TCA for 10 min, then, 2 % DEAE-cellulose removed protein and colored impurities. Purified VAP retained most of the radical-scavenging activities and GES-1 cell protection capability in vitro , indicating VAP were the key active components of V. axillare . Some molecular features were identified by FT-IR and NMR analyses. The molecular weight was estimated from DOSY NMR experiments to be around 21 kDa. There were 6.3 % uronic acid residues in the VAP. The constituent sugars after TFA hydrolysis were identified by HPLC to include glucose, arabinose, rhamnose, galactose, and xylose in a molar ratio of 405 : 259 : 82 : 42 : 1.
研究领域:
生药学
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生物化学
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药学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yujun Xie,Luyao An,Xiaoyan Wang,Yajie Ma,Alamusi Bayoude,Xinxin Fan,Boyang Yu,Renshi Li
Ethnopharmacological relevance Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. Aim of the study This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. Materials and methods The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. Results CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p -NF- κ B and p -I κ B- α expression levels and inhibiting the generation of IL-6, TNF- α , and IL-1 β . At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. Conclusion This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.
研究领域:
药理学
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植物化学
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胃肠病学
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分子生物学
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炎症研究
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氧化应激
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2022
·
IF 7.088
Xing-Rong Wang,Shuai Wang,Hong-Xia Mu,Kai-Yan Xu,Xue-Ting Wang,Jian-Tao Shi,Qi-Hang Cui,Li-Wen Zhang,Shi-Wu Chen
VEGFR-2 is an attractive therapeutic target for antitumor drug research by blocking tumor angiogenesis and PROTAC provides a new technology for targeted protein knockout. Herein, a library of novel VEGFR-2-PROTAC degraders were rationally designed and synthesized based on the Lys residue region on the surface of VEGFR-2 protein using protein structure-based drug design strategy. Among them, P7 exhibited preferable antitumor activity against HGC-27 cells and less toxic to human normal HUVEC, HEK293T and GES-1 cells in vitro , as well as the potent degradation activity of VEGFR-2 protein in HGC-27 cells (DC 50 : 0.084 ± 0.04 μM, D max : 73.7%) and HUVEC cells (DC 50 : 0.51 ± 0.10 μM, Dmax: 76.6%). Additionally, P7 degraded VEGFR-2 protein by the formation of ternary complex and the ubiquitin proteasome pathway in HGC-27 cells. Furthermore, P7 shortened the half-life of VEGFR-2 protein synthesis and had no inhibitory effect on the expression of VEGFR-2 mRNA in HGC-27 cells. Moreover, P7 inhibited the colony formation, migration and invasion of HGC-27 cells in a time- and dose-dependent manner, and meanwhile induced G 2 /M phase cycle arrest and apoptosis . All the results demonstrated that P7 could be as a promising VEGFR-2-PROTAC degrader for gastric cancer therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）