Salmonella Typhi (S. Typhi), a Gram-negative, serves as the etiological agent of typhoid fever. In contrast to other Salmonella serovars, S. Typhi exclusively infects humans. However, the molecular interactions it engages in with the host immune system remain inadequately characterized. This study adopts a multi-omics strategy to elucidate the immune and metabolic dynamics within the murine spleen during S. Typhi infection.

To identify and analyze transcriptomic, proteomic, and metabolomic alterations in the spleens of mice infected with S. Typhi. By comparing these host responses with those elicited by Salmonella Typhimurium (S. Typhimurium), a closely related serovar possessing a broad host range, the study seeks to uncover the unique metabolic reprogramming and immune-modulatory mechanisms specific to S. Typhi infection.

A multi-omics strategy was adopted, integrating transcriptomic, proteomic, and metabolomic data obtained from the spleen tissues of S. Typhi-infected mice. S. Typhimurium was utilized as a comparative control to distinguish host-specific responses. Additionally, the dynamics of reactive oxygen species (ROS), which play pivotal roles in mediating immune responses during infection, were examined.

Integration of multi-omics datasets demonstrated distinct metabolic and immunological responses orchestrated by S. Typhi infection. Host metabolism was reprogrammed by S. Typhi through the upregulation of glycolysis and the facilitation of glucose-to-pyruvate conversion, while concurrently suppressing the tricarboxylic acid cycle (TCA cycle). These changes culminated in increased lactate accumulation, and augmented ROS production, all of which were associated with intensified immune activation.

S. Typhi infection induces metabolic reprogramming in the host, characterized by a redirected glycolytic flux and altered pyruvate metabolism. This metabolic shift enhances ROS production and modulates the immune response. These findings yield novel insights into host-specific strategies employed by S. Typhi and highlight the significance of metabolic remodeling in immune defense, thereby presenting potential therapeutic targets for combating typhoid fever.

Hezi Qingyou Formula (HZQYF) is a clinical formulation known for its efficacy in treating gastrointestinal diseases. Nevertheless, its specific impact and underlying mechanism of action in gastric cancer remain to be fully elucidated. The major components of the formula were precisely identified and characterized using ultra-high-performance liquid chromatography coupled with a tandem mass spectrometer (UHPLC-MS/MS). Network pharmacology and transcript analysis were utilized to identify the targets associated with drug-disease interactions. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were conducted to unravel the pivotal pathways involved. Furthermore, in vitro experiments were performed to validate the anti-gastric cancer activity of HZQYF, including assessments of cell viability and clonogenic potential. These results revealed that 260 co-expressed targets were identified as shared between HZQYF and gastric cancer. These genes were significantly enriched in biological processes and pathways related to steroid metabolism, gamma-aminobutyric acid (GABA)-A receptor complex, steroid binding activity, extracellular ligand-gated ion channel activity, chemical carcinogenesis-reactive oxygen species, and GABAergic synapse. Furthermore, the principal components of the formula were characterized. Subsequent cell experiments confirmed the formula's ability to inhibit gastric cancer activity and suppress colony formation in vitro. In conclusion, these findings suggest that Hezi Qingyou Formula may exert its anti-gastric cancer activity by influencing reactive oxygen species and modulating GABAergic synapses in-silico methods. This study provides a foundation for further exploration of HZQYF as a potential therapeutic agent for gastric cancer.

Detection of Helicobacter pylori, Staphylococcus, Nocardia and Cyanobacteria inside the yeast Candida tropicalis raised the question whether treating yeast with antibiotics mix (ABM) eliminates intracellular bacteria. Live/Dead staining showed occurrence of viable bacteria inside the vacuole of C. tropicalis. Amplification of bacterial 16S rRNA genes from yeast DNA with the size of 521, 750, 606 and 450 bp were similar to those from control H. pylori, Staphylococcus, Nocardia and Cyanobacteria, respectively. To eliminate intracellular bacteria yeast cultures in yeast-glucose (YG) broth were treated with 32-1024 μg/mL of ABM (amoxicillin, ciprofloxacin, rifampin and metronidazole) for up to 24 h. Viability of treated yeast cells and their intracellular bacteria was assessed by colony count, Live/Dead staining and detection of bacterial 16S rRNA genes. Colony count of C. tropicalis exposed to 32-256 μg/mL of ABM (4.39-9.63) or 512-1024 μg/mL (9.67-9.77) were similar to their respected controls (p > 0.05). Amplification of similar bacterial genes from treated yeasts and controls confirmed persistent occurrence of intracellular bacteria. Micrographs of yeasts treated with 32-256 μg/mL of ABM showed intact yeasts and intracellular bacteria, however those treated with 512 and 1024 μg/mL showed occurrence of < 10% and > 10% yellow damaged yeasts, respectively that accumulated yellow rifampin. Fluorescence microscopy showed that both intact and damaged yeasts carried live bacteria inside their vacuole. Culture of treated yeasts on YG agar produced colonies with totally intact yeasts and intracellular bacteria. Yeast extruded antibiotics and reduced their effective concentration for killing intracellular bacteria. Establishment of bacteria inside the fungal vacuole cannot be disrupted with antibiotics.

Gastric cancer is highly correlated with Helicobacter pylori (H. pylori) infection. Approximately 50 % of the population worldwide is infected with H. pylori. However, current treatment regimens face severe challenges including drug resistance and gut microbiota disruption. An integrative treatment with slight negative influences on intestinal flora, conforming with concepts of integrative prevention of gastric cancer, is urgently needed. Non-antibiotic responsive biomaterials can respond to different stimuli, including pH, enzymes, light, ultrasound and magnetism, under which biomaterials are specifically activated to perform antibacterial capabilities, while neutral intestinal microenvironments differ from gastric microenvironments or inflammatory sites and have no or minimal irradiation via precisely controlled exogenous stimuli, which may not only overcome antibiotic resistance but also avoid gut microbiota disorders. First, the latest progress in responsive biomaterials against H. pylori without gut microbiome disturbance and their anti-H. pylori performances are profoundly summarized. Second, the mechanisms against planktonic bacteria, biofilms and intracellular bacteria are discussed respectively. Finally, the strategies of specific and targeted H. pylori elimination by responsive biomaterials are introduced. Additionally, the challenges and the focus of future research on translation into clinical application are fully proposed. Antibiotic-free responsive biomaterials for specific and targeted H. pylori eradication represent an innovative approach.

Infection with Helicobacter pylori is the major causative factor of chronic gastritis, peptic ulcer, gastric cancer, and other diseases. Gastric mucosal epithelial injury characterized by abnormal apoptosis, oxidative stress, and inflammation is a crucial mechanism of H. pylori infection. Hyperoside (HYP) is a flavonol glycoside derived from many herbal plants, which exhibits potent anti-apoptotic, antioxidant, and anti-inflammatory properties. Our research explored whether it exerts protective effects on H. pylori-infected human gastric epithelial cells. GES-1 cells were first treated for 24 h with HYP (0, 10, 20, 40, 80, 100, or 120 μM) to determine the cytotoxicity of HYP. Subsequently, GES-1 cells were pre-treated for 4 h with HYP (80 μM), followed by exposure to H. pylori for 24 h. CCK-8 assay, flow cytometry assay, ELISA, RT-qPCR, DCFH-DA staining, the commercial assay kits, immunofluorescence staining, and western blotting were used to assess cell viability, cell apoptosis, pro-inflammatory cytokine levels, oxidative stress marker levels, and Nrf2/HO-1 signaling-related molecule levels. The Nrf2 inhibitor ML385 was employed to verify the beneficial role of Nrf2 activation in HYP-mediated GES-1 cell injury induced by H. pylori. The results showed that HYP pre-treatment reversed H. pylori-induced cell apoptosis, inflammation, and oxidative stress in GES-1 cells. Furthermore, HYP downregulated Nrf2, HO-1, and NQO1 protein levels in H. pylori-infected GES-1 cells. ML385 overturned the protective effects of HYP against H. pylori-induced GES-1 cell apoptosis, inflammation, and oxidative stress. In conclusion, HYP protects gastric epithelial cells against H. pylori-induced cell injury by activating the Nrf2/HO-1 pathway.

This study aimed to assess the expression changes of BTG1, PGI, and PGII in tissues and serum of patients with gastric cancer, atrophic gastritis, and healthy individuals.

QRT-PCR was used to measure BTG1, PGI, and PGII expression in 30 cancers, 30 atrophic gastritis, and 30 healthy tissue samples. Serum levels of PGI and PGII were measured using ELISA. Statistical tests included the Mann-Whitney U and independent T-test. Covariates like tumour stage and H. pylori status were considered.

BTG1 expression was significantly lower in cancer and gastritis tissues. Serum PGI and PGII levels were significantly reduced in cancer patients (P ≤ 0.001).

The PGI/PGII ratio in serum emerged as a strong non-invasive biomarker for distinguishing cancer from healthy individuals. While BTG1 provides insights into gastric carcinogenesis, its clinical utility is limited due to the need for tissue samples. The serum-based PGI/PGII ratio shows greater promise as a non-invasive screening tool for GC.

Chitosan, a non-toxic and biodegradable compound, enhances plant growth and secondary metabolite production, presenting innovative approaches to mitigating plant stress. Salinity, a common abiotic stress, significantly impairs plant growth and development. This study investigates the effects of chitosan on the physiological, biochemical, and gene expression responses of salt-stressed Brassica napus L. exposed to NaCl concentrations of 0, 50, 100, and 150 mM. Chitosan was applied as a foliar spray at concentrations of 0, 5 and 10 mg/L. The research focuses on gene expression changes in P5CS, PIP, and PAL genes in the roots and shoots of Brassica napus, revealing notable alterations, particularly in PIP expression under saline conditions. The study also observed enhanced PAL enzyme activity, increased chlorophyll and proline levels, and changes in iron, potassium, and nitrogen content. These findings demonstrate chitosan's potential to improve plant resilience to salt stress. By modulating gene expression and enhancing physiological responses, chitosan presents a promising solution for enhancing plant tolerance to salinity, with valuable implications for agricultural practices.

This article employed a bidirectional Mendelian randomization (MR) analysis to deduce the causal relationship between H. pylori infection (Seven H. pylori antibodies: CagA, Catalase, GroEL, IgG, OMP, UREA, and VacA) and allergic diseases. This study primarily employed the Inverse-Variance Weighted (IVW)method, supplemented by MR-Egger regression and the Weighted median (WM) method approach, to comprehensively assess the causal relationship between exposure and outcome. Sensitivity analysis, including Cochran's Q test, MR-Egger regression intercept, MR-PRESSO test, and leave-one-out analysis, verified the reliability of the results. In the forward MR analysis, the IVW analysis outcomes showed the causal relationship existed between the allergic urticaria (AU) and Catalase antibody, allergic asthma (AA) and allergic rhinitis (AR) with OMP antibody, and allergic conjunctivitis (AC) and VacA antibody; in the reverse MR analysis, the results of the IVW analysis revealed that CagA antibody was positively associated with AU. Sensitivity analysis indicated that the causal relationship was robust. Higher levels of Catalase antibody may potentially increase the risk of AU development; increased OMP antibody levels might be associated with a higher risk for AA, yet could potentially be a protective factor against AR; greater VacA antibody levels might possibly decrease the incidence of AC; individuals with AU might have a higher likelihood of exhibiting elevated CagA antibody levels. It is suggested that H. pylori infection could potentially influence the onset and progression of allergic diseases via the "gut-skin", "gut-lung", "gut-nose", and "gut-eye" axis; moreover, skin diseases may potentially impact the gut microbiota imbalance through the "skin-gut" axis.

Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.

Oxidative stress contributes to the development of cardiometabolic diseases and cancers. Numerous studies have highlighted the adverse effects of high reactive oxygen species (ROS) levels in the progression of chronic noncommunicable diseases and also during infections. On the other hand, antioxidants play a crucial role in preventing oxidative stress or postponing cell damage via the direct scavenging of free radicals or indirectly via the Keap1/Nrf2/ARE pathway, among others. Dietary antioxidants can be obtained from various sources, mainly through a plant-based diet, including fruits and vegetables. The dietary antioxidant index (DAI) has been developed to assess total antioxidant intake from diet. This review delineated the performance of DAI in the risk assessment of different diseases. It is suggested that a high DAI score prevents obesity-related diseases, including diabetes mellitus, hyperuricemia, dyslipidemia, and metabolic (dysfunction)-associated steatotic liver disease (MASLD). Additionally, DAI is negatively associated with Helicobacter pylori and Human papillomavirus infection, thus reducing the risk of gastric and cervical cancer. Also, a high intake of antioxidants prevents the development of osteoporosis, miscarriage, infertility, and mental illnesses. However, further prospective observations and clinical trials are warranted to confirm the application of DAI in preventing diseases that have been studied.

One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.

Non-Helicobacter pylori Helicobacter (NHPH) species are emerging as significant gastric pathogens. Despite their clinical importance, NHPH infections are less studied compared to Helicobacter pylori (H. pylori) due to their lower prevalence and diagnostic challenges. Zoonotic transmission, particularly from pigs, dogs, and cats, underscores the need for improved diagnostic methods and heightened clinical awareness. Gastric cancer (GC) remains a major global health issue, with H. pylori being a primary risk factor. The eradication of H. pylori reduces GC risk, but post-eradication surveillance is essential. Endoscopic findings, especially those from the Kyoto classification, and noninvasive biomarkers play crucial roles in early GC detection and risk assessment. The increasing antibiotic resistance in H. pylori necessitates new treatment strategies. Novel therapies, such as vonoprazan-based regimens, and alternatives like sitafloxacin and rifabutin, are being developed to improve eradication success rates. Understanding the fundamental mechanisms of gastric carcinogenesis, including the roles of oxidative stress and cancer stem cells, is key to advancing treatment. Targeting specific molecular pathways offers potential for more effective therapies.

Introduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites. Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation. Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone. Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.

Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori (H. pylori) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group, Helicobacter, Bacteroides, Klebsiella, and Pseudomonas. In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori-positive (HP_Pos) and H. pylori-negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.

Chronic inflammation is known to increase the risk of gastrointestinal cancers (GICs), the common solid tumors worldwide. Precancerous lesions, such as chronic atrophic inflammation and ulcers, are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis. Unfortunately, due to the lack of effective therapeutic targets, the prognosis of patients with GICs is still unsatisfactory. Interestingly, it is found that six transmembrane epithelial antigens of the prostate (STEAPs), a group of metal reductases, are significantly associated with the progression of malignancies, playing a crucial role in systemic metabolic homeostasis and inflammatory responses. The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress, responding to inflammatory reactions. Under the imbalance status of abnormal oxidative stress, STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process. This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms, with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Peptic ulcer is a high incidence gastrointestinal disease in China. Berberine (BBR) is a natural product isolated from the Chinese herb Coptis chinensis Franch that has protective effects in digestive diseases. We aimed to evaluate the ability of BBR to attenuate acute gastric ulcer induced by one-time administration of ethanol in the rat.

Tissue pathological morphology, macroscopic score, ulcer healing rate, and serum levels of the inflammatory cytokines nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and anti-inflammatory interleukin-10 (IL-10) were used to determine the efficacy of BBR and evaluated to identify the optimal dosage. Subsequently, transcriptome and metabolome sequencing were conducted in Control, Model, and optimal dosage groups to explore the pathogenesis of the disease and the mechanism of action of the drug. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), as well as those of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by enzyme-linked immunosorbent assay to verify the results of transcriptomics and metabolomics analyses.

BBR significantly improved the pathological morphology of gastric ulcers, increased the macroscopic score and healing rate, decreased serum levels of NO, IL-6, and PGE2, and increased serum levels of IL-10, thus effectively alleviating gastric ulcer severity. Transcriptome results showed that the therapeutic effect of BBR was mainly mediated by the arachidonic acid metabolism pathway at the gene level, which is closely associated with inflammation and increased levels of reactive oxygen species (ROS). The differentially accumulated metabolite prostaglandin E1, which is a negative regulator of ROS, was significantly up-regulated after BBR administration. The validation results indicated that BBR pretreatment increased SOD and GSH-Px enzyme activities, while reducing levels of the oxidative products MDA and MPO.

This study demonstrated that BBR exerts a protective effect on acute gastric ulcer by promoting tricarboxylic acid cycle-mediated arachidonic acid metabolism.