CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yingnan Zhu,Yalan Ji,Fei Li,Wenwen Gao,Xinyu Xiao,Tiantian Xu,Jie Feng,Jiahang Si,Ruikang Zhang,Yuze Dong
Helicobacter pylori ( H. pylori ) infection, affecting more than half of the world's population, remains the primary etiological driver of stomach cancer. The efficacy of standard antibiotic-based quadruple therapy is declining due to the antibiotic resistance. To address this critical challenge, we developed an inflammation-responsive self-cascading reactive oxygen species (ROS) nanogenerator (BiPt@BSA-PpIX@AP) that synergizes nanozyme catalysis and sonodynamic therapy (SDT) for precision H. pylori eradication. Upon ultrasound activation, the system demonstrated dual-modal ROS amplification. BiPt nanozymes catalytically converted endogenous H 2 O 2 to •OH and O 2 , while protoporphyrin (PpIX) generated more 1 O 2 than free PpIX through enhanced sonoluminescence energy transfer. In H. pylori infected mouse model, the BiPt@BSA-PpIX@AP actively targeted submucosa colonized H. pylori owing to metalloproteinases (MMPs)-triggered hydrolysis and protonation effect, and further eradicated H. pylori and its biofilm by producing ROS. Unlike triple therapy, the nanogenerators had negligible side effects on the normal gut microbiota. This microenvironment-driven self-enhancing ROS nanogenerators have great potential for the treatment of H. pylori infection.
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BIOMATERIALS
·
2024
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IF 12.8
Zishan Zeng,Yue Sun,Jingwen Jiang,Xiaoyu Xu,Huanxin Lin,Wanzhen Li,Dong Zheng,Yanjuan Huang,Chunshun Zhao
Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori ( H. pylori ) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori . H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori -based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.
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Clinical and Experimental Gastroenterology
·
2026
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IF 2.6
Jingwen Xu,Chengbo Zhang,Yan Jiang,Rumeng Wang,Yang Liu,Ning Zhang,Yugang Liu,Lizhou Jia
Objective To explore the antibacterial effect of ginkgolic acid (GA) modified into liposome nanoparticles (TLM@GA) against Helicobacter pylori and investigate the antibacterial mechanism involved to provide a lead drug for radical clinical treatment.Methods A new complex that improved GA stability and bioavailability was constructed using liposome nanoparticles (TLM@GA). The construction of the complex was verified by Fourier transform infrared spectroscopy, scanning electron microscopy, Zeta potential, and particle size detection, and its physicochemical properties were comprehensively evaluated. An acute gastritis model was also established using C57BL/6 mice, in which the in vivo therapeutic effect of TLM@GA was evaluated by detecting the colonization amount of the clinical multi-resistant strain HPBS001 in the gastric mucosa. Additionally, the pathological inflammation of the gastric mucosa was observed with H&E staining, apoptosis of gastric mucosal cells was observed with TUNEL staining, and the expression of serum inflammatory factors was detected with enzyme-linked immunosorbent assay. The in vivo safety of TLM@GA was evaluated by detecting its effect on mouse body weight and the damage to the stomach, liver, spleen, and kidneys.Results The TLM@GA complex had excellent stability and dispersibility. The minimum inhibitory concentration of GA against H. pylori strains was 16–32 μg/mL, and that of TLM@GA was 0.25–0.5 μg/mL. After GA was modified into TLM@GA, its antibacterial activity was 32–128 times higher. After treatment with TLM@GA (28 mg/kg), the colonization of H. pylori in the gastric mucosa was significantly reduced, which was better than that in the omeprazole and amoxicillin (dual-therapy) and GA groups. Apoptotic and inflammatory cells in the gastric mucosa were significantly reduced, indicating alleviated inflammation. After treatment, the expression levels of major inflammatory factors were significantly decreased. There was no significant change in body weight when mice were intragastrically administered 140 mg/kg TLM@GA for 1 week, and no obvious pathological damage was found in the stomach, liver, spleen, or kidneys.Conclusion TLM@GA had excellent stability, efficient release, and good loading capacity efficiency. It was significantly superior to GA in terms of in vitro antibacterial activity, had low toxicity, was not prone to drug resistance, and demonstrated high safety. TLM@GA demonstrated a good antibacterial effect in the in vivo acidic environment, effectively slowing the apoptosis of gastric mucosal cells and significantly reducing levels of inflammatory factors, alleviating the inflammatory response.
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CLINICA CHIMICA ACTA
·
2025
·
IF 2.9
Yanghe Liu,Sijie Yin,Shiyue Chen,Chunlei Zhang,Nasifu Lubanga,Ping Tai,Mengqiu Xiong,Boyue Fan,Xincheng Yang,Xinyi Xia,PanFei Hou,Bangshun He
Helicobacter pylori ( H. pylori ) is a risk factor of gastrointestinal diseases. Vacuolating cytotoxin A (VacA) is a key component of the pathogenicity of H. pylori for gastric diseases , and detection for virulence genotypes facilitates precise clinical diagnosis and individual treatment. Hence, a more accurate, convenient, and highly sensitive detection method is urgently needed. In this study, we developed a method based on fluorescence-colorimetric dual-indicator loop-mediated isothermal amplification (FC-LAMP), allowing for naked-eye readout, using a constant temperature water bath within 40 min in clinical settings. Such an excellent sensitivity and specificity, and user-friendly operation approach achieved a limit of 10 −6 ng/μl for 16 s rRNA detection of H. pylori , and 100 % specificity for 55 clinical gastric fluid samples compared with the immunofluorescence staining (IFS) and quantitative polymerase chain reaction (qPCR) as reference methods. In short, this study offers a new strategy for detection of H. pylori and its virulence genotype in primary hospitals and in limited resources settings, facilitating individualized precision eradication of H. pylori .
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Frontiers in Microbiology
·
2024
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IF 4
Feng Zhong,Li Hui,Hao Yajie,Peng Chang,Ou Ling,Jia Junwei,Xun Mingjin,Zou Yuanjing,Chen Meiyun,Zhang Guimin,Yao Meicun
Background: Helicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism.Methods: Chemical components of HZQYF were studied using UHPLC–MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF’s antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein.Results: Minimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80–160 μg/mL, and minimum bactericidal concentration (MBC) values were 160–320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity.Conclusion: Present studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations.
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HELICOBACTER
·
2025
·Vol. 30
·期 4
·e70058
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IF 4.3
Yalan Zhu,Jiaxue Yang,Chubin Fang,Chuan Wang,Tian Tang
Background The current first-line treatment for Helicobacter pylori ( H. pylori) infection is bismuth-based quadruple therapy. However, the widespread use of antibiotics has contributed to the emergence of antibiotic-resistant strains, thereby increasing the likelihood of treatment failure. This study aimed to develop a multi-epitope H. pylori vaccine, designated P22-C3, based on P22 Virus-like Particles, with the objective of reducing infection rates and preventing transmission. Materials and Methods The structural characteristics of P22-C3 were analyzed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The safety profile of P22-C3 was evaluated through a series of in vitro and in vivo assays. In vitro assessments included cytotoxicity and proinflammatory factor testing. In vivo evaluations, conducted in immunized mice, involved monitoring changes in body weight, biochemical marker fluctuations, and histopathological examinations. The antibody response and T cell-mediated immunity elicited by P22-C3 were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Immune protection efficacy was assessed through a challenge experiment. Results P22-C3 successfully self-assembled into T = 7 icosahedral structures with an average diameter of 58 nm. Both in vitro and in vivo experiments confirmed that P22-C3 was safe and well-tolerated. Furthermore, P22-C3 elicited a dose-dependent IgG response and a mixed Th1/Th17 immune profile. In challenge experiments, mice immunized with P22-C3 demonstrated reduced bacterial loads and urease levels in the stomach. Conclusion P22-C3 was well-tolerated and successfully induced a strong immune response, offering protection against H. pylori infection. These properties make P22-C3 a promising H. pylori vaccine. It is important to note that this study was conducted solely in mice and did not involve human participants; therefore, a clinical trial registration number is not applicable.
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Biomed Research International
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2022
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IF 3.246
Chuanying Li,Rong Cheng,Lin Li,Miaomiao Chen,Cheng Wu
Duodenal ulcer seriously affects the quality of life and life safety of children, but the pathogenesis of children with duodenal ulcer is still unclear. As an important second messenger in the body, Ca2+ participates in the physiological and pathological processes of various diseases. Therefore, transient receptor potential vanilloid type 4 (TRPV4) as one of the channels that mediate Ca2+ has attracted widespread attention in recent years. Here, we found that TRPV4 is highly expressed in children with duodenal ulcer and has good diagnostic value through specimens of children with duodenal ulcer, and animal experiments have proved that TRPV4 is also highly expressed in duodenal ulcer mice. In addition, TRPV4 can enhance intestinal permeability, thereby promoting further infiltration of inflammatory factors. In summary, these results indicate that TRPV4 is involved in the occurrence and development of duodenal ulcer. Therefore, this study provides the diagnostic and therapeutic value of TRPV4 in children with duodenal ulcer.
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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2024
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IF 4.1
Hongming Huang,Huang Yang,Shunhang Feng,Xiaoyan Zhang,Chu Chen,Hongyu Yan,Rui Li,Mengxin Liu,Juan Lin,Yancheng Wen,Feifei She
The burgeoning emergence of drug-resistant Helicobacter pylori strains poses a significant challenge to the clinical success of eradication therapies and is primarily attributed to mutations within drug-targeting genes that lead to antibiotic resistance. This study investigated the effect of high salt conditions on the occurrence of drug-resistance mutations in H. pylori. We found that high salt condition significantly amplifies the frequency of drug resistance mutations in H. pylori. This can be chiefly attributed to our discovery indicating that high salt concentration results in elevated reactive oxygen species (ROS) levels, initiating DNA damage within H. pylori. Mechanistically, high salt condition suppresses lipopolysaccharide (LPS) synthesis gene expression, inducing alterations in the LPS structure and escalating outer membrane permeability. This disruption of LPS synthesis attenuates the expression and activity of SodB, facilitates increased ROS levels, and consequently increases the drug resistance mutation frequency. Impairing LPS synthesis engenders a reduction in intracellular iron levels, leading to diminished holo-Fur activity and increased apo-Fur activity, which represses the expression of SodB directly. Our findings suggest a correlation between high salt intake and the emergence of drug resistance in the human pathogen H. pylori, implying that dietary choices affect the risk of emergence of antimicrobial resistance.
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JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Zhanlin Zhang,Dandan Zhang,Guiyuan Zhang,Junwu Wei,Jie Meng,Xiaohong Li
Helicobacter pylori ( H. pylori ) infection is a major etiological factor in diverse gastric pathologies, accounting for approximately 75 % of gastric cancer cases. Current clinical antibiotic therapy faces significant challenges due to drug resistance, gastric acid degradation, and the formidable barriers of gastric mucus and biofilm matrix. To tackle these challenges, antibiotic-loaded nanomotors were developed for self-propelled penetration through gastric mucus and biofilm matrix to achieve H. pylori eradication. Specifically, Janus-structured J-Ca/Si@PDA-CLR nanoparticles (NPs) were fabricated by sequentially depositing mesoporous silica layers onto CaO 2 NPs and asymmetrically coating them with clarithromycin (CLR)-loaded polydopamine (PDA). CaO 2 reacted with gastric acid and produced O 2 , combined with the intrinsic Janus coating, generates an asymmetrical protrusion force, enabling effective mucus penetration and preventing premature gastric emptying. The protection of mesoporous silica layers ensures long-term motion, more rapid and complete penetration across mucus layers, and deep infiltration into biofilms, enhancing drug retention in the stomach and targeted accumulation within biofilms. Following intragastrical administration in H. pylori -infected mice, the nanomotors exhibited efficient infiltration into submucosal tissues and deep distribution throughout the stomach wall, in stark contrast to their static counterparts confined to the gastric surface. Treatment with the nanomotors resulted in an 8000-fold reduction in gastric bacterial burden compared to static carriers. Remarkably, nanomotors given at half the CLR dose produced a 75-fold higher bactericidal effect compared to free CLR at twice the dose. Thus, this work establishes a feasible therapeutic strategy utilizing self-propelled NPs to overcome mucus barriers and achieve deep biofilm clearance, demonstrating significant potential for applications in treating biofilm-associated infections.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2026
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IF 15
Wei Zhang,Yanan Zhou,Zijun Li,Zhaowen Wang,Fangzheng Zhu,Yaoyu Zou,Nianshuang Li,Cong He,Nonghua Lu,Xiaolei Wang,Yin Zhu
Helicobacter pylori (H. pylori) infection has emerged as a serious risk factor for global human health. Current antibiotic-based clinical eradication therapies still have many challenges, including inadequate drug permeability across the gastric mucus barrier, H. pylori biofilm-induced antibiotic resistance and recurrent infections, as well as gut dysbacteriosis. Herein, we report a probiotic-nanozyme hybrid system (LP@FeTA/CuPt), which is formed by coupling polyphenol-coated Lactobacillus plantarum (LP@FeTA) and CuPt nanozymes. LP@FeTA effectively penetrates the gastric mucus barrier via autokinetic movement, and facilitates the targeted delivery of CuPt nanozymes within H. pylori biofilms by "eating" extracellular polymeric substances (EPS). CuPt nanozymes respond to the acidic and H 2 O 2 -rich biofilm microenvironment to generate reactive oxygen species (ROS) and release Cu ions, thereby achieving multi-target eradication of biofilms by interfering with H. pylori flagellar self-assembly, urease activity, outer membrane function and energy metabolism. Importantly, LP@FeTA/CuPt can be degraded by transferrin at the infection site, allowing the released CuPt nanozymes to reactivate the antibacterial immune functions of macrophage, thus eliminating biofilm-escaped bacterioplankton to prevent recurrent infections. Notably, LP@FeTA/CuPt also modulates gut microbiota homeostasis. This study provides a promising non-antibiotic therapeutic strategy for H. pylori infection.
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Long Ma,Yajie Liu,Yongpo Mao,Jiayi Wang,Yiping Chen,Fei Deng,Zhiwei Zhu,Lanxiang Ou,Myunghee Kim,Shengying Ye,Weipan Peng,Shuli Man
Helicobacter pylori ( H. pylori ) infection poses a significant threat to public health. In this work, we combined Thermus thermophilus A rgonaute ( Tt Ago) with l oop-mediated isothermal amplification (LAMP) to establish a t ri-color fluorescent biosensing for detection and genotyping of H . p ylori from human salivary samples, termed as ALT- Hp . Leveraging the programmability, site specific cleaving-activity of Tt Ago, ALT- Hp enabled the multiplexed detection of H. pylori -specific genes ureA , vacA , and cagA . Furthermore, a customized 3D-printed visualizer compatible with App-enabled smartphones was developed, highlighting its potential for on-site detection. ALT- Hp utilized the amplification capability of LAMP and the signal transduction and amplification “lighting-up” functions of Tt Ago, for building a highly sensitive, specific and robust platform for on-site detection. It demonstrated robust performance in complex matrices, achieving a LOD of 1 CFU/mL within 30 min. Clinical validation using 72 samples showed 100% sensitivity and specificity. ALT- Hp was not only able to detect H. pylori , but also capable of genotyping by classifying H. pylori as type I and type II. The classification is primarily based on whether the strains carry virulence factors, and the two types differed significantly in pathogenicity and clinical outcomes, serving as a critical reference for clinical diagnosis and treatment decision-making. Thus, this ALT- Hp biosensing represented a powerful molecular diagnostic tool for monitoring and management of H. pylori infections.
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ACS Nano
·
2022
·
IF 18.027
Xin Xia,Zhiwei Yin,Yanxia Yang,Shengkai Li,Linlin Wang,Xinqi Cai,Yiting Xu,Chao Ma,Ye Qiu,Zhuo Chen,Weihong Tan
Taking inspiration from the mechanism of Helicobacter pylori infection can lead to innovative antibacterial ways to fight antibiotics resistance. Herein, a gastric nano-heater iron–cobalt alloy shielded with graphitic shells (FeCo@G) is developed to interfere with H. pylori infection under an alternating magnetic field. FeCo@G shows a high and stable specific loss power (SLP = 534.1 W g-1) in the acidic environment and provides efficient magnetothermal stimulation in the stomach. Such stimulation upregulates the cytoprotective heat shock protein 70 (HSP70) in gastric epithelial cells, which antagonizes the infection of H. pylori. This finding is further supported by the transcriptomic analysis verifying the upregulation of HSP70 in the stomach. Moreover, the nano-heater shows a high inhibition rate of H. pyloriin vivo with good biocompatibility; 95% of FeCo@G is excreted from the mouse’s gastrointestinal tract within 12 h. In summary, FeCo@G allows magnetothermal therapy to be used in harsh gastric environments, providing an approach for the therapy against H. pylori.
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