The contribution of IL-17A-dependent low LCN2 levels to Helicobacter pylori infection: Insights from clinical and experimental studies.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a common bacterial infection that is widespread globally. It is crucial to comprehend the molecular mechanisms that underlie the infection caused by H. pylori in order to devise successful therapeutic approaches. The objective of this study was to examine the involvement of Lipocalin-2 (LCN2) in the development of H. pylori infection. METHODS: LCN2 expression levels in human gastric mucosa and H. pylori-infected mouse models were analyzed using quantitative PCR and immunohistochemistry methods. The effects of LCN2 on the attachment of H. pylori to gastric mucosa cells were assessed using bacterial culture and fluorescence intensity tests. To investigate the correlation between LCN2, CCL20, and IL-17A, we performed gene expression analysis and measured serum levels. RESULTS: The findings indicated an increase in LCN2 levels in the gastric mucosa of both patients and mice infected with H. pylori. Blocking the natural LCN2 resulted in an increased attachment of H. pylori to cells in the gastric mucosa. In addition, we noticed that reduced levels of LCN2 promoted the attachment of H. pylori to cells in the gastric mucosa. Furthermore, H. pylori-infected patients exhibited increased expression of both LCN2 and CCL20, and there was a positive correlation between serum levels of CCL20 and LCN2. LCN2 expression was found to depend on the presence of IL-17A, and inhibiting IL-17A led to a higher H. pylori colonization. CONCLUSION: The persistence of H. pylori infection is facilitated by the presence of low levels of LCN2, which is dependent on IL-17A. This finding offers valuable perspectives for the development of novel therapeutic approaches for H. pylori infection.

Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case-control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism 'TC' genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35-.63), p < .001]. GC cases with dominant genetic model 'TC + CC' had a 47% reduced risk of GC [OR, 95%CI: .53 (.40-.71), p < .001]. Subgroup analyses revealed that the rs733618 'TC + CC' genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31-.58), p < .001], those aged ≤60 years old [OR, 95%CI: .27 (.18-.42), p < .001], non-drinkers [OR, 95%CI: .21 (.13-.33), p < .001], non-smokers [OR, 95%CI: .38 (.25-.57), p < .001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10-.26), p < .001]. Further multivariated analyses indicated that individuals with the 'TC + CC' rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29-.83), p = .032] and had no H. pylori infection [OR, 95%CI: .35 (.28-.76), p = .018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with 'TC' and 'TC + CC' genotypes (all p < .05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.

A ferroptosis-related gene in Helicobacter pylori infection, SOCS1, serves as a potential prognostic biomarker and corresponds with tumor immune infiltration in stomach adenocarcinoma: In silico approach.

OBJECTIVE: Helicobacter pylori (H. pylori) is a major risk factor for the stomach adenocarcinoma (STAD). This study aimed to investigate the potential role of a H. pylori infection-related gene, SOCS1, in STAD. MATERIALS AND METHODS: Online available databases were analyzed to determine the expression, correlations with clinicopathologic parameters, patients' survival, and immunological characteristics of SOCS1 in TCGA-STAD or GEO datasets. Univariate and multivariate Cox regression analyses were used to determine independent risk factors, which were further integrated to establish a nomogram. A comparison of drug sensitivity was conducted for the chemotherapy responses between individuals with low- and high-SOCS1. Prediction of tumor response to checkpoint inhibitors was based on the tumor immunodeficiency and exclusion (TIDE) score. RESULTS: SOCS1 expression was significantly increased in both H. pylori-infected and STAD patients. Higher SOCS1 expression indicated an undesirable prognosis in STAD patients. SOCS1 upregulation was related to enhanced immune cell infiltrations and the upregulation of immune checkpoints in STAD patients. N stage, age and SOCS1 were identified as independent risk factors for higher mortality of STAD patients and confirmed using the nomogram. Drug sensitivity analyses demonstrated that high expression of SOCS1 in STAD patients could improve the sensitivity to chemotherapy. TIDE score showed that STAD patients with high SOCS1 expression would have superior response to immunotherapy. CONCLUSIONS: SOCS1 may act as a potential biomarker for uncovering the underlying mechanisms of gastric cancer. Increasing the activity of immunotherapy through ferroptosis-immunomodulation may be a viable strategy in STAD therapy.

Evaluation of the diagnostic and prognostic values of serum HSP90α in sepsis patients: a retrospective study.

Background: Sepsis is a serious syndrome that is caused by immune responses dysfunction and leads to high mortality. The abilities of heat shock protein 90α (HSP90α) in assessing the diagnosis and prognosis in patients with sepsis remain ill-defined to date. We conducted a study to reveal the possible clinical applications of HSP90α as biomarker for the diagnosis and prognosis in patients with sepsis. Methods: In total, 150 patients of sepsis, 110 patients without sepsis admitted to ICU and 110 healthy subjects were involved in this study. The serum HSP90α contents, sequential organ failure assessment (SOFA) scores, procalcitonin (PCT), and short-term survival status of the participants were measured and compared. Logistic and linear regression models adjusting for potential confounders were used to examine the association of HSP90α with sepsis survival. Moreover, serum IL-1ß, IL-18, MIP-3α, and ENA-78 were also determined. Finally, Spearman correlation analysis was employed to reveal a possible mechanism that HSP90α contributed to the short-term deaths. Results: Serum HSP90α levels in sepsis patients were higher than those in ICU controls and healthy controls (P < 0.001), and even increased in patients who died within 28 days (P < 0.001). Logistic and linear regression models identified HSP90α was an independent risk factors for sepsis mortality. Receiver operating characteristic (ROC) analysis displayed that HSP90α had a considerable predictive performance for sepsis outcome, with an area under curve (AUC) value up to 0.79. Survival analysis demonstrated that the mortality of sepsis individuals at 28 days was positively associated with HSP90α levels, especially the levels of HSP90α were greater than 120 ng/mL (P < 0.001). Moreover, among sepsis patients, those who died had notably elevated cytokines, IL-1ß, IL-18, and chemokines, MIP-3α, ENA-78, relative to survivors. Further correlation analysis demonstrated that there was a nominally positive correlation between HSP90α and IL-1ß, IL-18, and MIP-3α. Conclusion: HSP90α is of favorable clinical significance in sepsis diagnosis and prognosis, laying a foundation for future clinical applications.