Advanced Science
·
2023
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IF 15.1
Jiayin Yu,Zhihao Guo,Jiachang Yan,Changxin Bu,Chang Peng,Cuie Li,Rui Mao,Jian Zhang,Zhi Wang,Shi Chen,Meicun Yao,Zhiyong Xie,Chuan Yang,Yi Yan Yang,Peiyan Yuan,Xin Ding
Helicobacter pylori ( H. pylori ) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H 2 O 2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H 2 O 2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.
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Advanced Science
·
2024
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IF 14.3
Xuemei Liu,Qiaofen Chen,Shiyuan Xu,Jiaying Wu,Jingwen Zhao,Zhengfu He,Aiwu Pan,Jianmin Wu
Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2025
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IF 4.2
Huilin Zhao,Shuzhen Liu,Jiangfan Shan,Juan Zhang,Qianwen Wu,Jianhui Zhang,Zekun Sun,Xinying Cao,Shu Chen,Mingzhu Feng,Yinuo Zhang,Xiang Cheng,Boqing Li,Xiaofei Ji
CagA, one of the key virulence factors of Helicobacter pylori , plays a significant role in H. pylori -associated gastric cancer by actively participating in neoplastic transformation. Among CagA variants, East Asian type CagA (CagA E ) bearing the EPIYA-D motif exhibits a higher risk than the Western-type (CagA W ) with EPIYA-C motifs. In this study, we investigated the interactions of CagA E and CagA W and host intracellular Grb2 and found a pronouncedly greater recruitment of Grb2 by CagA E compared to CagA W . Our findings revealed the phosphorylated tyrosine in the EPIYA motif is very important for the binding of CagA to Grb2. Phe at Y + 5 position in EPIYA-D, which interacts with Trp 121 in SH2 domain of Grb2, established the higher affinity than the interaction of EPIYA-C and Grb2-SH2. The substitute of Phe to Asp/Ala in CagA E EPIYA-D reduced the recruitment of Grb2 by CagA E , and neutralized the stronger induced malignant characteristics of the recipient cells. These findings provide additional insights into the distinct regulatory mechanisms employed by CagA E and CagA W , contributing to a better understanding of the higher oncogenic risk associated with H. pylori CagA E .
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Frontiers in Microbiology
·
2024
·
IF 4
Qian Jiali,Li Zhennan,Wang Jinhui,Lin Yuxian,Yu Yingcong
The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 μg/mL for JF-1, 40 μg/mL for JF-2, 30 μg/mL for JF-3, 40 μg/mL for JF-4, 60 μg/mL for 6-gingerol standard (SS), and 0.03 μg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.
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Virulence
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2024
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IF 5.5
Xiaofei Ji,Qianwen Wu,Xinying Cao,Shuzhen Liu,Jianhui Zhang,Si Chen,Jiangfan Shan,Ying Zhang,Boqing Li,Huilin Zhao
CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.
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mBio
·
2026
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IF 5.4
Luan Luan,Xiuling Song,Yunfei Zeng,Yunyun Xie,Yongxuan Hong,Jiawei Tang,Cong Ma,Bing Gu,Liang Wang
Gastric cancer remains a major global health burden, ranking fifth worldwide in both incidence and mortality. While Helicobacter pylori is a well-established Group I carcinogen, increasing evidence suggests that non-H. pylori bacteria, including Streptococcus anginosus, may also contribute to gastric carcinogenesis. However, their comparative pathogenic roles and interactions remain poorly defined. In this study, public databases showed stage-dependent abundance changes of H. pylori and S. anginosus but no significant correlation during gastric cancer progression. We further quantified both bacteria in gastric fluid samples collected from 500 individuals using a non-invasive gastric string test and in fecal samples from an independent cohort of 500 individuals by qPCR. In the two cohorts, no significant correlations were observed between the two bacterial pathogens, suggesting distinct colonization and pathogenic patterns. To evaluate functional differences, AGS cell co-culture models were established to explore their pro-tumorigenic effects. H. pylori predominantly exerted tumor-promoting effects through bacterial cell-associated mechanisms, whereas S. anginosus exerted stronger pro-tumorigenic effects via its metabolites. In particular, transcriptomic analysis revealed that proliferation-associated genes, including DEK and RTF1, were significantly upregulated by 21.9-fold and 19.2-fold, respectively, in cells treated with Streptococcus anginosus metabolite (SAM). Metabolomic profiling of SAM identified increased levels of spermidine and polyamine-related metabolites. Among these, N-acetylcadaverine, N-acetyltyrosine, N-acetyltryptophan, and urocanic acid were experimentally validated to significantly promote AGS cell proliferation. Collectively, these findings demonstrate that H. pylori and S. anginosus drive gastric tumorigenesis through contact-dependent and metabolite-mediated mechanisms, respectively, highlighting bacterial metabolites as emerging contributors to gastric cancer progression.
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MICROCHEMICAL JOURNAL
·
2026
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IF 5.2
Ren-Min Zhou,Ying Chen,Yu-Shuang Zheng,Kai Wang,Guo-Rong Tang,Qiong Lin
Helicobacter pylori ( H. pylori ) is a gram-negative, spiral-shaped, microaerophilic bacterium that specifically colonizes the human gastric mucosa. Distinguished as the sole microorganism capable of surviving the harsh acidic environment of the stomach, this unique adaptation underpins its pivotal role in the onset and progression of gastric diseases. Consequently, H. pylori is recognized as the primary etiological agent of chronic gastritis, a condition that presents significant global health challenges. This work reports the development of a newly engineered hemicyanine-based molecular probe, designated HD-WY , for the real-time and highly sensitive quantification of hydrogen sulfide (H 2 S), a key gaseous signaling molecule involved in gastritis and associated disease mechanisms. The HD-WY probe functions via an H 2 S-specific activation mechanism, which induces a marked enhancement in both optical absorption and fluorescence intensity. Exhibiting a linear response to H 2 S concentrations, the probe achieves a low detection limit of 160 nM. In cellular assays, the probe effectively monitored real-time variations in endogenous H 2 S levels, with approximately 17-fold fluorescence increase from the 2.5 μM HD-WY group to the 10.0 μM group and approximately 3-fold fluorescence from the 0 min group to the 60 min group, validating its utility for the early detection and continuous observation of gastritic conditions. A notable finding was the probe's capacity to differentiate between healthy controls and gastritis patients, demonstrating a marked increase (approximately 50-fold) in fluorescence output within patient-derived samples, thereby highlighting its diagnostic potential. Complementary histopathological evaluation using hematoxylin and eosin (H&E) staining further verified distinct morphological changes in gastric tissues from gastritis subjects relative to healthy counterparts. The demonstrated high specificity, robust stability, and excellent biocompatibility of the HD-WY probe under physiological settings underscore its promising utility in clinical diagnostic procedures and biomedical research, furnishing a dependable tool for non-invasive disease monitoring and facilitating timely therapeutic strategies.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
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IF 5.4
Qin Tang,Zhengcai Ma,Xiang Tang,Yan Liu,Huimin Wu,Yu Peng,Baihua Jiao,Rui Wang,Xiaoli Ye,Hang Ma,Xuegang Li
Ethnopharmacological relevance Helicobacter pylori (H. pylori) is a major pathogen colonized in the human stomach and is implicated in gastritis, peptic ulcer, and gastric carcinoma. Antibiotics are useful for eradicating H. pylori but failed for drug resistance, making it urgent to develop effective and safe drugs. Rhizoma Coptidis was reported as one of the most effective Chinese medicines to treat H. pylori -related gastrointestinal diseases, while the precise antimicrobial mechanism remains unclear. Thus, it is of great significance to study the antimicrobial ingredients and corresponding mechanisms of Rhizoma Coptidis. Aim of the study To search for the most effective alkaloid against H. pylori in Rhizoma Coptidis and illustrate the probable mechanisms . Materials and methods Five main alkaloids in Rhizoma Coptidis were isolated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested to determine the most effective one. Bacterial growth experiments, Annexin V-FITC/PI staining, TUNEL staining, and transmission electron microscopy (TEM) were performed to further study the anti- H. pylori activity of coptisine (Cop) . The in vivo effect of Cop on H. pylori eradication rate and H. pylori -induced inflammation was investigated in mice . Transcriptomics was used to understand the underlying mechanism of eradicating H. pylori and reducing host inflammation. Western blot, RT-PCR, and ELISA experiments were utilized and confirmed that cagA was one of the targets of Cop. Results According to the MIC and MBC, Cop was the most effective alkaloid against H. pylori , especially with no drug resistance developed . In vitro experiments showed that Cop inhibited H. pylori by inducing DNA fragmentation, phosphatidylserine exposure, and membrane damage. Cop (150 mg/kg/day) effectively eradicated H. pylori in mice and reduced the levels of IL-2 and IL-6 to relieve gastric inflammation. Transcriptomic analysis revealed that virulence factor cagA was one of the hub genes associated with the inflammation-improving effect of Cop. That is, Cop could decrease the expression of CagA and subsequently reduce the translocation of CagA to gastric epithelial cells, thereby improving the morphology of hummingbird-like phenotype induced by CagA and alleviating inflammation . Conclusions Cop is the most effective alkaloid in Rhizoma Coptidis and might act through multiple mechanisms for H. pylori eradication along with reducing the expression of CagA to alleviate inflammation.
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MICROBIAL PATHOGENESIS
·
2019
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IF 2.581
Xiaonan Chen,Pengyu Li,Yuanna Shen,Yiqing Zou,Gang Yuan,Haiyan Hu
Antibiotics resistance of H. pylori has been increasing constantly accompanied with decreasing clearance rate clinically, which is demonstrated to be closely related to biofilms with higher resistance than planktonic bacteria for the dense extracellular polymeric substances . Rhamnolipid (RHL) is proved to not only damage the structure of biofilm, but also potentially inhibit bacterial adhesion . To investigate if RHL could promote eradicating rate of the conventional triple therapy to H. pylori biofilm and hence attenuate the resistance and relapse of H. pylori , first-line antibiotics clarithromycin (CLR), amoxicillin (AMX) or/and proton pump inhibitor (PPI) involved single, dual or triple therapies were compared with RHL-containing drug combinations on eradicating H. pylori biofilm. The residual biofilm biomass, the survival of bacteria inside the remaining biofilm and the planktonic bacteria dispersed from the biofilm after treatment were tested. Combination with RHL significantly improved the ability of antibiotics to eradicate H. pylori biofilm, especially RHL combined with AMX and PPI could eradicate more than 95% of biofilm showing much more effective ability than the conventional triple therapy CLR + AMX + PPI. Additionally, the combination of RHL and antibiotics could effectively inhibit the biofilm formation at lower concentration. Thus, RHL might be used as a potential antibiotic adjuvant on anti- H. pylori therapy to enhance eradicating ability of antibiotics to biofilms.
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Research
·
2024
·
IF 8.5
Chunxi Shu,Wei Zhang,Yiwei Zhang,Yu Li,Xinbo Xu,Yanan Zhou,Yue Zhang,Qin Zhong,Cong He,Yin Zhu,Xiaolei Wang
Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of “bacterioplankton ↔ biofilm”, thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.
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Advanced Healthcare Materials
·
2024
·
IF 10
Jinjie Fan,Yuze Dong,Yue Sun,Yalan Ji,Jie Feng,Peijuan Yan,Yingnan Zhu
Helicobacter pylori ( H. pylori ) infection is closely associated with the development of various gastric diseases. The effectiveness of current clinical antibiotic therapy is hampered by the rise of drug-resistant strains and the formation of H. pylori biofilm. This paper reports a sonodynamic nanocomposite PtCu 3 -PDA@AIPH@Fucoidan (PPAF), which consists of dopamine-modified inorganic sonosensitizers PtCu 3 , alkyl radicals (R•) generator AIPH and fucoidan, can penetrate the mucus layer, target H. pylori , disrupt biofilms, and exhibit excellent bactericidal ability. In vitro experiments demonstrate that PPAF exhibits excellent acoustic kinetic properties, generating a significant amount of reactive oxygen species (ROS) and oxygen-independent R• for sterilization under ultrasound stimulation. Simultaneously, the produced N 2 can enhance the cavitation effect, aiding PPAF nanoparticles in penetrating the gastric mucus layer and disrupting biofilm integrity. This disruption allows more PPAF nanoparticles to bind to biofilm bacteria, facilitating the eradication of H. pylori . In vivo experiments demonstrated that ultrasound-stimulated PPAF exhibited significant antibacterial efficacy against H. pylori . Moreover, it effectively modulated the expression levels of inflammatory factors and maintained gastrointestinal microbiota stability when compared to the antibiotic treatment group. In summary, PPAF nanoparticles present a potential alternative to antibiotics, offering an effective and healthy option for treating H. pylori infection. This article is protected by copyright. All rights reserved
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Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Yao Yang,Xiao-Fen Jia,Guang-Hui Cui,Qiu-Yue Huang,Miao-Miao Lin,Zong-Ming Shi,Hui Ye,Xue-Zhi Zhang
Background Helicobacter pylori (H. pylori) infection represents a prevalent global health burden. Current eradication strategies are complicated by increasing antibiotic resistance and detrimental alterations to the gut microbiome. Jinghuaweikang capsule (JWC), a traditional Chinese medicine, has demonstrated efficacy against H. pylori , yet its mechanisms involving microbiota-inflammation interactions remain incompletely elucidated. AIM This study aimed to investigate the effects of the JWC on gastric mucosal inflammation and the expression of drug-resistance genes in H. pylori -infected mice. Methods Sixty Kunming mice were randomly allocated into six groups, including normal control group (Control), model group (Model), Western medicine triple group (AC), low-dose JWC group (JWCL), medium-dose JWC group (JWCM), and high-dose JWC group (JWCH). A mouse model of H. pylori infection was established by intragastric administration of an H. pylori SS1 solution for two weeks. The efficacy of this model was evaluated using rapid urease test (RUT) and Warthin-Starry (WS) silver stain. Subsequently, the experimental cohort of mice underwent pharmacological intervention. Hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess the impact of JWC on inflammation within the gastric mucosa of mice infected with H. pylori . Metagenomic sequencing technology was used to identify alterations in the intestinal microbiota and antibiotic resistance genes in the murine models. Western blotting was used to assess the expression levels of proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Results JWC mitigated gastric mucosal inflammation induced by H. pylori infection and reduced the concentrations of interleukin- (IL-) 6, IL-1β, and tumor necrosis factor-α (TNF-α) while inhibiting gene expression level. Metagenomic sequencing revealed that triple therapy in Western medicine markedly diminished the diversity of the intestinal microbiota while elevating the abundance of antibiotic-resistance genes, including macB , arlR , evgS , tetA(58) , and mtrA . The diversity and richness of the intestinal microbiota in the JWC group were comparable to those in the control group, with an increase in the abundance of beneficial bacteria such as Muribaculaceae_bacterium . Furthermore, the expression levels of the antibiotic resistance genes macB , tetA(58) , bcrA , oleC , and arlS were downregulated. Moreover, the activation of MAPK signaling pathway components phospho-ERK and phospho-p38 was inhibited. Conclusion JWC preserves microbial diversity and promotes a beneficial compositional shift, mitigates the risk of antibiotic resistance, modulates the MAPK signaling pathway, and alleviates gastric mucosal inflammation in mice infected with H. pylori .
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