CELL
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2024
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IF 45.5
Kaili Fu,Alvin Ho Kwan Cheung,Chi Chun Wong,Weixin Liu,Yunfei Zhou,Feixue Wang,Pingmei Huang,Kai Yuan,Olabisi Oluwabukola Coker,Yasi Pan,Danyu Chen,Nga Man Lam,Mengxue Gao,Xiang Zhang,He Huang,Ka Fai To,Joseph Jao Yiu Sung,Jun Yu
Summary Streptococcus anginosus ( S. anginosus ) was enriched in the gastric mucosa of patients with gastric cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (ANXA2) receptor on gastric epithelial cells. Interaction of TMPC with ANXA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. ANXA2 knockout abrogated the induction of MAPK by S. anginosus . Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.
研究领域:
微生物学
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肿瘤学
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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
Scientific Reports
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2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Yang Le,Wang Jie,Li Peng,Guo Yuxi,Li Siyuan,Liu Shuangyu,Lou Yingying,Qi Jinlong,Yang Qian
Gastric cancer (GC) is a severe malignancy characterized by late diagnosis, poor prognosis, and low survival rates. Its progression is often linked to chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG), which show atypical symptoms. Identifying biomarkers for CNAG, CAG, and GC progression is crucial for earlier diagnosis and prevention. This study conducted non-targeted metabolomics on 81 clinical samples (17 controls; 23, 23, and 18 from CNAG, CAG, and GC patients, respectively) using ultra-high-performance Liquid chromatography and high-resolution mass spectrometry. A total of 763 metabolites were identified, of which eight metabolic pathways were in dysregulation at different disease stages. Disease progression showed pronounced disruptions in amino acid, Lipid, and microbial metabolism. Targeted metabolomics identified 56 metabolites, with significant differences in O-(4,8-dimethylnonanoyl) carnitine and dehydroepiandrosterone sulfate (DHEAS). DHEAS and L-threonic acid (L-TA) were validated as biomarkers, with detection methods developed and applied to confirm their clinical significance. These findings enhance understanding of CNAG, CAG, and GC progression and provide validated biomarkers for potential clinical application in GC diagnosis and treatment.
研究领域:
肿瘤学
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消化病学
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代谢组学
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分子生物学
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转化医学
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疾病 biomarker 发现
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Xing Li,Jipeng Zhang,Xiangyu Liu,Zijian Wu,Zhipeng Yu,Wen Zhang,Yuanzhi Wang,Zekun Li,Martien A. Cohen Stuart,Leonard M.C. Sagis,Minchun Lv,Jie Xiao,Yuan Li
Helicobacter pylori ( H. pylori ) is a prevalent global pathogen responsible for gastritis and the potential development of gastric cancer. Sulforaphane (SFN), a foodborne compound, exhibits notable antibiotic properties against H. pylori . However, its utility is limited by poor stability and susceptibility to environmental degradation. Here, we developed a gastric-responsive-release microgel for delivering anti- H. pylori SFN. The microgels were prepared by cross-linking α-lactalbumin nanotubes then coated with chitosan (CTS-MGs). SFN was loaded into microgels with a loading rate of 10.73 ± 0.25 %. The CTS-MG showed a strong adhesion to the gastric mucosa, prolonging gastric retention for up to 24 h and responsively releasing SFN in the stomach. Furthermore, CTS-MG/SFN dissociated and released nanotubes/SFN, which could penetrate into the gastric mucus layer and arrive at the deepest mucus sites where most H. pylori were colonized. Our results revealed that CTS-MG/SFN displayed an obvious inhibitory effect against H. pylori . The oral administration of CTS-MG/SFN in H. pylori -infected mice effectively alleviated H. pylori -induced gastritis and modulated gastric microbiota homeostasis. This work demonstrated high potential of CTS-MG microgels for gastric-targeted and oral delivery of antibiotic natural compounds against H. pylori infection.
研究领域:
药学
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微生物学
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生物材料学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Jiaying Liu,Yuanfan Chen,Jing Zhang,Yun Zheng,Yun An,Chenglai Xia,Yonger Chen,Song Huang,Shaozhen Hou,Dong Deng
Ethnopharmacological relevance The dried fruit of Crataegus pinnatifida Bunge (Hawthorn in Chinese) is a traditional medicine used in China, Japan and Korea for thousands of years. Hawthorn is documented in the Chinese Pharmacopoeia , as a folk medicine that is used to eliminate food, strengthen the stomach, move qi and dissipate blood stasis, treat stagnation of meat and food, gastric distention and fullness, and has anti-inflammatory effects. Vitexin, a flavonoid glycoside, is an important biologically active compound derived from Hawthorn, with significant antioxidant and anti-inflammatory properties. The pharmacological effects of Hawthorn are highly correlated with the antioxidant and anti-inflammatory effects of vitexin. Aim of the study The aim of the present study was to investigate the effect of vitexin on the alleviation of chronic atrophic gastritis (CAG) induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) in a rat model, as well as to elucidate the underlying mechanisms involved. Materials and methods CAG was administered at a concentration of 170 μg/mL MNNG in the drinking water of rats, and the effects of vitexin (30 mg/kg, once daily for 6 weeks) on gastric tissues were subsequently analyzed. Pathological damage was assessed using H&E and AB-PAS staining. Gastrointestinal hormone levels, specifically motilin (MTL) and gastrin (GAS), were quantified using biochemical index determination kits. To evaluate the levels of cytokines, specifically IL-1β and IL-18, in gastric tissue, an enzyme-linked immunosorbent assay (ELISA) was performed. Additionally, to investigate the effects of vitexin on the NLRP3 inflammasome, GES-1 cells were subjected to treatment with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The targeting of NLRP3 by vitexin was assessed in vitro using CESTA, DARTS, and a synthesized biotin-labeled vitexin probe (biotin-vitexin) in conjunction with dual immunofluorescence. RT-PCR, Western blotting and immunofluorescence were used to evaluate the ameliorative effect of oysterin on LPS + ATP-induced GES-1 cells in vitro. Results Administration of vitexin significantly alleviated the symptoms of chronic atrophic gastritis (CAG) by reducing weight loss and minimizing gastric tissue damage. Treatment with vitexin in CAG rats effectively reduces the production of pro-inflammatory cytokines. Furthermore, vitexin attenuated the activation of the NLRP3 inflammasome in CAG induced by MNNG. Mechanistic experiments showed that NLRP3 is a direct cellular target of vitexin, while vitexin inhibited rat NLRP3 inflammasome. Conclusion Vitexin mitigates MNNG-induced CAG, and its protective effect is linked to the inhibition of NLRP3 inflammasome activation.
研究领域:
药理学
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民族药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
·
IF 2.63
Yuling Tong,Manyi Jing,Xu Zhao,Honghong Liu,Shizhang Wei,Ruisheng Li,Xia Liu,Min Wang,Hongtao Song,Yanling Zhao
The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.
研究领域:
中药学
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代谢组学
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病理学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Da Feng,Li Guo,Yihan Zhao,Fang Yuan,Lulu Ning,Yuan Guo,Jianjian Zhang
Real-time monitoring of the lysosomal microenvironment using small-molecule probes is critical for understanding the complex interactions between organelles and diseases associated with lysosomal dysfunction. Most traditional fluorescent-dye-based lysosome probes rely on the protonation of the nitrogen atom in the morpholine unit to visualize the lysosomal microenvironment by inhibiting the photoinduced electron transfer (PET) effect. However, these probes often face selectivity issues within the complex cellular microenvironment. For instance, classic hemicyanine dyes (HD) show nonspecific fluorescence responses in the liver due to inappropriate pKa value, leading to low imaging contrast and the risk of false positives. Herein, a series of novel pH/viscosity-activatable, lysosomal-targeted near-infrared (NIR) fluorescent probes were developed by incorporating naphthalimide dye with hemicyanine dyes. These probes exhibit no fluorescence at physiological pH and weak fluorescence under acidic conditions (key 1), with substantial fluorescence activation triggered by abnormal viscosity in pathological tissues (key 2). Notably, NpCy-4 demonstrated a superior signal-to-background ratio (SBR) for cellular imaging and proved effective for real-time in situ diagnosis of acute gastritis.
研究领域:
生物化学
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医学影像学
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分子生物学
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DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2024
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IF 1.8
Jiang Qianqian,Fan Guoxia,Wu Kaiwei
Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N’-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.
研究领域:
肿瘤学
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胃肠病学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 6
·791
·
IF 4.8
Xiaojie Wang,Miaomiao Chang,Kun Feng,Qingyue Wang,Bowen Li,Weijuan Gao
Background:Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear.Methods:A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels.Results:Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-O-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway.Conclusions:The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives.
研究领域:
药理学
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肿瘤学
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胃肠病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Qi Liu,Wei-Wei Ni,Zhen Li,Cai-Fu Bai,Dan-Dan Tan,Chang-Jun Pu,Dong Zhou,Qing-Peng Tian,Ni Luo,Kai-Li Tan,Le Dai,Yuan Yan,Yong Pei,Xian-Hui Li,Zhu-Ping Xiao,Hai-Liang Zhu
The continuing emergence of drug-resistant Helicobacter pylori (HP) drives the ongoing need for the development of new and effective anti-HP drugs. Urease inhibitor has now gained strong interest as an alternative approach for HP infections . 3-Chlorophenyl-3-hydroxypropionylhydroxamic acid (CPH), a novel urease inhibitor identified in our group, shows impressive potency, which was optically separated for a further exploration. Here, we report in vitro / in vivo pharmacological evaluation of (±)-CPHs and the enantiomers. The raceme and the individual enantiomers significantly suppress gastritis at 32 mg/kg b.i.d dose with lower toxicity to mammalian cells (with CC 50 s ≥ 3.16 mM) and mice (LD 50 s ≥ 2338 mg/kg) than the clinically used agent acetohydroxamic acid . Furthermore, a significant increase of eradication of HP is observed for the combination of (±)-CPHs or the enantiomers with an antimicrobial. These studies revealed that CPH is a promising candidate for an alternative treatment of HP-dependent conditions by targeting virulence factor urease, and CPH may be used as a raceme.
研究领域:
药理学
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微生物学
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感染病学
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DOI
PubMed
高影响因子
PLoS One
·
2020
·Vol. 15
·期 11
·e0236203
·
IF 2.74
Guo-Xiu Zu,Qian-Qian Sun,Jian Chen,Xi-Jian Liu,Ke-Yun Sun,Liang-Kun Zhang,Ling Li,Tao Han,Hai-Liang Huang
Background/aim
To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG).
Materials and methods
Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method.
Results
Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism.
Conclusion
By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.
研究领域:
医学科学
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代谢组学
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胃肠病学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jia Liu,Mengyu Li,Guobao Chen,Junhui Yang,Ying Jiang,Fang Li,Haibing Hua
Ethnopharmacological relevance Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. Purpose To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. Methods In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. Results Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin , paeoniflorin , lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability , migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 μg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot , immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. Conclusion JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.
研究领域:
药理学
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中医中药
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Tong Yuling,Liu Liping,Wang Ruilin,Yang Tao,Wen Jianxia,Wei Shizhang,Jing Manyi,Zou Wenjun,Zhao Yanling
The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.
研究领域:
药理学
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胃肠病学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
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