CELL
·
2024
·
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
·
胃肠病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Liping Han,Ting Li,Yingying Wang,Weizi Lai,Hengpu Zhou,Zhuangwei Niu,Jie Su,Guiyuan Lv,Guangji Zhang,Jianli Gao,Jianbo Huang,Zhaohuan Lou
Ethnopharmacological relevance Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. Aim of the study The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. Methods The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin , pepsinogen , and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6 , IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy , respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. Results WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2 , and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. Conclusion This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways’ activation.
研究领域:
药理学
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胃肠病学
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中医
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
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
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2015
·
IF 2.998
Sheng Wang,Yang Zhao,Junqing Zhang,Xiaoxing Huang,Yifei Wang,Xiaotao Xu,Bin Zheng,Xue Zhou,Huajie Tian,Li Liu,Qibing Mei
Ethnopharmacological relevance The fructus Alpinia oxyphylla Miq. (AOM) has been used for treating diarrhea with spleen deficiency and gastralgia for thousands of years. A number of traditional Chinese medicine formulae provide AOM as an alternative herbal treatment for diarrhea, but the scientific basis for this usage has not been well defined. Aim of the study In this study, we tried to investigate the antidiarrheal activity and possible mechanisms of Fructus AOM, aiming to enrich our understanding to the scientific meanings and theoretical significance of Fructus AOM in clinical practice. Materials and methods The fructus of AOM collected from Hainan province in China were macerated in the 95% ethanol to obtain the crude 95% ethanol extract, followed by subjected to chromatographic separation over a Diaion HP20 column to obtain 90% and 50% ethanol eluted fractions. The activities of the crude extract and fractions on castor oil induced acute diarrhea , rhubarb induced chronic diarrhea , gastrointestinal transit (GIT) in mice, and contractions of isolated guinea-pig ileum were evaluated. Additionally, nitric oxide (NO), gastrointestinal peptides gastrin (GAS), motilin (MTL) and somatostatin (SS) levels that related to gastrointestinal motilities were detected to demonstrate the potential mechanisms. Ultimately, LC–MS/MS method was utilized to ensure the chemical consistency. Results The 95% ethanol extract and 90% ethanol eluted fraction significantly delayed the onset time and decreased the wet faeces proportion compared with control group in the castor oil induced acute diarrhea mice. In terms of further evaluation of antidiarrheal activity, the 95% ethanol extract and 90% ethanol elution displayed significant inhibition of the intestinal propulsion at the two highest oral doses of 20 g crude drug/kg and 1 g/kg. Moreover the 95% ethanol extract (10 and 20 g crude drug/kg) and 90% ethanol elution (0.5 and 1 g/kg) could significantly inhibit the GIT, which was partially attributed to the increase in NO and SS levels, and the decreased MTL. In vitro spontaneous contractions of the isolated guinea pig ileum induced by carbachol , neostigmine and histamine were attenuated by both the extract and elution. Phytochemical analysis of 95% ethanol extract and its fractions identified the presence of diphenylheptanes, sesquiterpenes , and flavones as the major components. Conclusions Our in vivo and in vitro data could partly support and justify the traditional usage of Fructus AOM on the treatment of diarrhea in traditional medicine.
研究领域:
药理学
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传统中药研究
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消化系统疾病
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DOI
高影响因子
Food Frontiers
·
2021
·Vol. 2
·期 3
·305-315
·
IF 0
Erdong Yuan,Liangyun Liu,Min Huang,Bo Chang,Chunli Qi,Na Gou,Jiaoyan Ren
Five complex extracts (CEs) of seven Chinese herbs ( Astragalus , Poria cocos , Alpinia officinarum Hance , Radix Puerariae , Ginseng , Licorice , Hericium erinaceus ) were prepared by hot water extraction and evaluated for their effect on gastric ulcer in rats. In rats with acetic acid-induced chronic gastric ulcer, gross and microscopic appearance showed that gastric mucosal injury index and lesion inhibition rate were improved after CEs gavage for 21 days. Pretreatment with CEs for 21 days in rats with acute gastric ulcer could also improve the gastric mucosal injury by ethanol. CE1, CE4, and CE5 showed more obvious effect in two models. The cell experiments results showed that CE1, CE4, and CE5 effectively inhibited Wnt signaling activity. Thus, they could protect gastric mucosa through inhibiting Wnt signaling pathway. These results indicated that CE1, CE4, and CE5 had significant protective effects on gastric mucosal injury by inhibiting Wnt signalling pathway and could be developed into safe functional products.
研究领域:
药理学
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胃肠病学
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中医
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产品关联
DOI
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
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
Food & Function
·
2023
·Vol. 14
·期 20
·9324-9336
·
IF 6.1
Hui Yang,Yingying Hou,Yujie Pan,Tingting Zhang,Qi Meng,Jianzhong Han,Weilin Liu,Daofeng Qu
Chewing ability has a strong effect on food digestion. However, little is known about the relationship between the food mastication degree and the subsequent gastric emptying. This study was to explore the effects of individual chewing ability (strong and weak) on the in vivo oral processing characteristics and in vitro dynamic gastrointestinal starch hydrolysis of three types of rice (japonica rice, indica rice and waxy rice). Results showed that the swallowable bolus in the weak chewing group had larger holes and a looser microstructure with more small rice particles, while the strong chewing ones obtained a bolus with higher saliva content (up to 28%) and starch hydrolysis degree (up to 13.55%). Moreover, the gastric retention and starch hydrolysis of the strong chewing ability group were higher in the artificial gastric dynamic system (AGDS). The indica rice particles with the higher degree of fragmentation contacted enzymes easier and hydrolyzed quicker, thus emptying through the stomach faster (81.76%). However, the oral chewing properties of rice mainly influenced the starch digestion in the stomach and the initial stage of the small intestine (∼5 min). This study suggested that the chewing ability and rice variety can influence the bolus properties, which in turn affected the gastric emptying and the degree of starch hydrolysis during digestion.
研究领域:
食品科学
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消化生理学
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2011
·Vol. 3
·期 2
·498-503
·
IF 0
Haoxiang Lu,Wei Wang,Zhen Zheng,Peiyu Sun,Xinling Wang,Feng-Chih Chang
Two kinds of novel peptide mimetic pepsin-inspired degradable polyurethanes were synthesized and characterized. A synthetic pseudo tripeptide acted as chain extender and provided active sites for pepsin biodegradation. In vitrodegradation behavior was investigated in simulated gastric fluid containing pepsin, and assessed by 1H NMR, mass loss and SEM. The results indicated that the pseudo peptide bonds in polyurethanes were effectively digested by the action of pepsin. Furthermore, the rate and degree of pepsin-inspired polyurethanes in simulated gastric fluid containing pepsin could be controlled by alteration of the soft segments and activity of pepsin. The influence of the polymers on human umbilical vein endothelial cells was evaluated by WST-1 assay. The results indicated that the polymers sustained much higher cell viability than the controls.
研究领域:
生物材料学
·
高分子化学
·
生物医学工程
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产品关联
DOI
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Nana Chen,Jing'e Niu,Qian Li,Jianyin Li,Xinping chen,Yuan Ren,Guotai Wu,Yingqian Liu,Yanbin Shi
To better treat gastric diseases and lower systemic side effect, it is essential to design new vectors to control drug release in stomach. Aiming to this challenge, we developed a new gastroretentive drug delivery system : nanomicelles-loaded gastroretentive beads. Firstly, the chitosan-coated emodin-loaded nanomicelles were developed and characterized. In vitro cytotoxicity of emodin-loaded nanomicelles, emodin suspensions and blank nanomicelles was evaluated with human gastric carcinoma SGC-7901 cells by MTT , indicating that the blank nanomicelles had null cytotoxicity and emodin-loaded nanomicelles had better antitumor efficacy compared with emodin suspensions. Secondly, nanomicelles-loaded floating mucoadhesive beads (NFM-Beads) were prepared, and the swelling, degradation, mucoadhesion and floating ability in vitro were separately investigated. FT-IR spectroscopy was applied to identify the formation of nanomicelles and NFM-Beads. Emodin release from NFM-Beads in vitro was fitted to anomalous transport mechanism. In vivo gastroretention behavior of NFM-Beads was evaluated by BaSO 4 -based X-ray imaging exams, showing that NFM-Beads can be retained in rabbit stomach for at least 8 h. Overall, the new NFM-Beads system could be an effective approach to improve the therapeutic potency of drug against gastric cancer.
研究领域:
药学
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药物递送系统
·
药理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Yihui Wang,Yujing Sun,Jie Yang,Lei Dai,Na Ji,Liu Xiong,Qingjie Sun
Nanoparticles (NPs) can form a protein corona (PC) with proteins in biological fluids. We examined whether starch nanoparticles (SNPs) form a PC and interact with digestive enzymes in simulated gastric and intestinal fluids. We investigated the adsorption of pepsin and trypsin on unmodified, carboxyl-, and amino-modified SNPs (SNPs, COOH-SNPs, and NH2-SNPs, respectively). Quartz crystal microbalance data showed that a tight and irreversible pepsin corona formed on the NH2-SNPs, pepsin had little or no binding to the SNPs and COOH-SNPs, and trypsin had weak binding to all three kinds of NPs. Dynamic light scattering data showed that pepsin significantly increased the size of the NH2-SNPs from 120 ± 2.6 to 203 ± 12.2 nm and decreased their surface potential from 23.2 ± 1.0 to 12.7 ± 0.2 mV. NH2-SNPs could induce the fluorescence quenching of pepsin and change its secondary structures without affecting its activity.
研究领域:
食品科学
·
生物化学
✓ 已验证
DOI
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Jie Zhao,Shuaiqian Wang,Diandian Jiang,Chong Chen,Jie Tang,Igor Tomasevic,Weizheng Sun
The stability behaviors of oxidized SPI emulsions under in vitro gastric conditions and the effects of pepsin diffusion on the proteolysis of emulsions were investigated using a static gastric model and the fluorescence recovery after photobleaching method. Results showed that protein oxidation increased the particle size of droplets and decreased the viscoelasticity of the interfacial layer. Compared to the control group (82.81 m 2 /s), the pepsin diffusivity decreased to 68.52 m 2 /s (7LA + LOX group) due to the space hindrance of oil droplets. After gastric digestion, protein hydrolysates were re-absorbed on the oil–water interface and formed a thick layer, thereby decreasing the size of oil droplets and reducing the contents of free amino acids in gastric digesta. The protein oxidation may affect the adsorption of interfacial proteins and alter the distribution of droplets, decreasing pepsin diffusion and ultimately impairing the emulsion gastric digestion. And this should be considered in the design of emulsion as the controllable delivery system.
研究领域:
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
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
✓ 已验证
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）