Diabetes mellitus is associated with a high risk of developing gastric cancer (GC). Metformin, which is conventionally used to treat type 2 diabetes, induces AMP-activated protein kinase signaling ...and suppresses gluconeogenesis. Recent studies have reported that metformin is associated with beneficial effects in cancer prevention and treatment owing to its anti-tumor effects. This makes metformin a potential medication for GC therapy. However, contradicting reports have emerged regarding the efficacy of metformin in reducing the risk of GC. This review summarizes the impact of metformin on mitigating GC risk by analyzing clinical databases. The mechanism underlying the anti-tumor effect of metformin on GC is also discussed.
Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich ...microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.
Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid ...rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori-associated diseases.
Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain ...controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%); however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and
infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.
Infection with Helicobacter pylori (H. pylori) has been linked to various gastro-intestinal diseases; nevertheless it remains to be clarified why only a minority of infected individuals develop ...illness. Studies from the West have indicated that the cagA gene and the associated EPIYA genotype of H. pylori is closely linked to the development of severe gastritis and gastric carcinoma; however, as yet no consistent correlation has been found among the bacteria from East Asia. In addition to genotype variation, the CagA protein undergoes fragmentation; however, the functional significance of fragmentation with respect to H. pylori infection remains unknown. In this study, we isolated 594 H. pylori colonies from 99 patients and examined the fragmentation patterns of CagA protein using immunoblotting. By analyzing the ability of the isolates to induce the host cell morphological transition to the highly invasive hummingbird phenotype, we demonstrated that H. pylori colonies with substantial CagA fragmentation are less potent in terms of causing this morphological transition. Our results uncovered a functional role for CagA fragmentation with respect to H. pylori-induced hummingbird phenotype formation and these findings suggest the possibility that the post-translational processing of CagA may be involved in H. pylori infection pathogenesis.
•HDDT, which given PPI and amoxicillin more than twice daily, possesses a satisfactory H. pylori eradication rate.•HDDT has the same H. pylori eradication rate as guideline therapies.•HDDT harbours a ...lower adverse effect risk compared to guideline therapy in both first-line and rescue therapies.•HDDT is more effective in high antibiotic-resistant circumstances.
Resistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent.
This study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study.
Several open public databases, including Cochrane, EMBASE, PubMed, and MEDLINE, were searched. The results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapies were analysed. Notably, 14 out of the 16 included studies were conducted in Asian regions.
The eradication rate of HDDT was lower but not significantly different from those of control therapies (odds ratio OR = 0.92, 95% confidence interval CI = 0.67–1.26) in the intent-to-treat (ITT) analysis. A similar trend was observed in the per-protocol (PP) analysis (OR = 0.88, 95% CI = 0.47–1.63). Notably, the adverse effect risk in HDDT was significantly lower than in other therapies (I2 = 67.75%, OR = 0.42, 95% CI = 0.33–0.54, P = 0.00004). When the eradication rate of the control group was lower than 81%, HDDT was significantly better than control therapies (OR = 2.44, 95% CI = 1.23–4.84).
HDDT used four times a day for 14 days showed better efficacy and safety than the guideline treatments for H. pylori infection in areas with high antimicrobial resistance.
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Helicobacter pylori infection is associated with high incidence of gastric diseases. The extensive therapy of H. pylori infection with antibiotics has increased its resistance rates worldwide. ...Ovatodiolide, a pure constituent isolated from Anisomeles indica, has been demonstrated to possess bactericidal activity against H. pylori. In this study, ovatodiolide inhibited the growth of both H. pylori reference strain and clinical multidrug-resistant isolates. Docking analysis revealed that ovatodiolide fits into the hydrophobic pocket of a ribosomal protein, RpsB. Furthermore, ovatodiolide inhibited bacterial growth by reducing levels of RpsB, which plays a crucial role in protein translation. Our results demonstrate that ovatodiolide binds to a ribosomal protein and interferes with protein synthesis. This study provides evidence that ovatodiolide has the potential to be developed into a potent therapeutic agent for treating H. pylori infection.
The aim of the present study was to investigate the antitumor effect and mechanism of action of hyperforin in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. Cells were treated with different ...concentrations of hyperforin for different periods of time. Effects of hyperforin on cell viability, apoptosis signaling, and expression of anti-apoptotic and proliferative proteins cellular FLICE-like inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia 1(MCL1), and cyclin-D1 were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and western blotting. Hyperforin significantly inhibited cell viability and expression of anti-apoptotic and proliferative proteins. We also found that hyperforin significantly induced accumulation of cells in sub-G
phase, loss of mitochondrial membrane potential, and increased levels of active caspase-3, and caspase-8. Taken together, our findings indicate that hyperforin triggers inhibition of tumor cell growth by inducing intrinsic and extrinsic apoptotic pathways in HCC SK-Hep1 cells.
Phellinus linteus, a species of mushroom, has been shown to contribute to health benefits, such as anti-inflammatory activity and immunomodulatory efficacy. The aim of this study was to analyze the ...most effective constituents of P. linteus fermented broths, polysaccharides, and to evaluate their immunoregulatory effects on T cells. Four fermented broths (PL1–4) and the dialyzate medium (MD) were prepared from P. linteus mycelia, and the polysaccharide contents of each were analyzed. The P. linteus samples were tested for biological activity in the regulation of T cell activation. In T cells, the production of mitogen-induced interleukin (IL)-2 and cell cycle progression were dose-responsively inhibited by PL3 and MD, primarily through cell-cycle arrest in S phase. PL3 broth, which contained large quantities of polysaccharides, significantly decreased the ratio of interferon-gamma (IFN-γ) to interleukin 4 (IL-4) in T cells. Thus, P. linteus fermented broths produced additive effects on the regulation of the Th1/Th2 balance and show promise for the development of immunomodulatory therapeutics.
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