Search Results (48)

Background: Enzymes secreted by the digestive glands are excreted from the body with urine, sweat and feces, and they are also removed from the blood due to their participation in the enzymatic provision of the secretion entering the gastrointestinal tract. Objective: The aim of this work was to analyze the activity of pepsinogen, amylase and lipase in the coprofiltrate of pregnant women in each trimester of pregnancy and in the postpartum period, taking into account the timing and type of delivery (term, premature, late delivery or cesarean section). Methods: Data from studies of non-pregnant (n = 45) and pregnant (n = 193) women were analyzed. The materials for preparation coprofiltrate were collected during delivery. Pepsinogen activity was determined by proteolytic activity at pH = 1.5–2.0 using the tyrosine spectrophotometric method, while amylase activity was determined by the amyloclastic method of Karavey, and lipolytic activity was determined by a unified kinetic method using olive oil as a substrate. Outcomes: A small amount of pepsinogen was excreted in the coprofiltrate, and while the level of its excretion increased after childbirth, it remained below the control values. At the same time, an increase in the amylolytic activity of the coprofiltrate was observed in all groups of pregnant women examined from the first to the third trimester of pregnancy. In pregnant women, multidirectional changes in lipase activity were observed depending on the timing and type of delivery. Conclusions: At the end of pregnancy, amylolytic activity increased in all women, and pepsinase activity decreased compared to the indicators of non-pregnant women. No reliable differences were found in the lipolytic activity of the coprofiltrate in pregnant women at the end of pregnancy and the indicators of non-pregnant women. Full article

Background/Objectives: Periostracum Cicadae (PC) is commonly used to treat chronic atrophic gastritis (CAG), but its underlying mechanisms are unclear. We investigated the therapeutic effects, active ingredients and molecular mechanisms of PC on CAG. Methods: We analyzed the components in the serum extract of PC by UHPLC-Q-Orbitrap-MS/MS. Then, we used rat and cell models to assess the impact of PC on CAG and employed network pharmacology and bioinformatics to predict key targets and active ingredients. Finally, we confirmed hub targets through experiments and molecular docking. Results: A total of 22 components were identified in the PC extract-containing serum using UHPLC-Q-Orbitrap MS/MS. Network pharmacology combined with molecular docking revealed that the protective effect was primarily mediated by three compounds: (Z)-akuammidine, chicoric acid, and columbianadin. And we revealed that c-Fos/c-Jun signaling pathways were crucial in therapy. PC extract-containing serum inhibited the vitality, migration, invasion, and multiplication of MC cells (model cells for CAG), induced apoptosis, and caused G0/G1 phase cell cycle arrest. The expression level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and gastrin 17 (G17) in the serum of CAG rats increased, while the expression level of pepsinogen I (PG I) and pepsinogen II (PG II) decreased. After 12 weeks of PC administration, these conditions were significantly improved. PC not only reduced the levels of antigen KI-67 (Ki67) and tumor protein p53 (P53) but also enhanced SRY-box Transcription Factor (SOX2). Simultaneously, PC down-regulated the expression of N-cadherin and Vimentin while up-regulating that of E-cadherin. Conclusions: PC inhibited epithelial–mesenchymal transition (EMT) via the c-Fos/c-Jun signaling pathway, thereby providing therapeutic benefits for CAG. Our study elucidates the mechanisms and material basis of PC in treating CAG, providing experimental evidence to support its clinical application. Full article

Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response. Full article

Background/Objectives: Although Helicobacter pylori (H. pylori) eradication therapy is important for preventing gastric cancer (GC), the occurrence of GC after H. pylori eradication remains a problem. In this study, the aim was to identify risk factors for GC after H. pylori eradication by comparing long-term histological, endoscopic, and serological evaluations of patients with and without GC. Methods: Patients who underwent H. pylori eradication therapy at Oita University Hospital between June 1997 and August 2013 and were followed for at least 3 years with long-term endoscopy, histology, and serum biochemical tests were included, and the GC (215 cases) and non-GC (11 cases) groups were compared. Results: The GC group was older than the non-GC group at the time of eradication, had lower serum pepsinogen I/II levels, had severe endoscopic atrophic changes, had higher activity at the antrum, and inflammation and intestinal metaplasia (IM) at the corpus on updated Sydney system scoring. On long-term follow-up after eradication, the GC group had a wider range of endoscopic mucosal atrophy and a lower serum pepsinogen I/II ratio at any time point. Conclusions: Endoscopic mucosal atrophy and the serum pepsinogen I/II ratio are useful predictors of GC in patients post H. pylori eradication at any time point. Full article

Background: Increased demand of the serological biomarker test (GastroPanel^®) in non-invasive diagnosis of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, prompted the design of GastroPanel^® Quick test (GPQT) (Biohit Oyj, Helsinki, Finland) for point-of-care (POC) settings. Objective: This study validated the diagnostic accuracy (DA) of GPQT in diagnosis of AG and Hp among gastroscopy referral patients. Methods: Altogether, 266 patients were enrolled among the consecutive gastroscopy referrals at the Department of Gastroenterology, Fortis Hospital (Punjab, India). All patients underwent gastroscopy with biopsies (n = 249) classified using the Updated Sydney System (USS) and finger prick blood sampling for GPQT testing. Results: Biopsy-confirmed AG was found in 15.3% (38/249) of the patients. The overall agreement between the GPQT and the USS classification was 71.4% (95% CI 65.4–77.0%), with the weighted kappa (κ_w) of 0.823 (95% CI 0.773–0.862). In ROC analysis for moderate/severe AG of the corpus (AGC) endpoint, AUC = 0.990 (95% CI 0.979–1.000) and AUC = 0.971 (95% CI 0.948–0.995) for PGI and PGI/PGII, respectively. Hp IgG Ab test detected biopsy-confirmed Hp with AUC = 0.836 (95% CI 0.783–0.889). Conclusions: The GPQT favourably competes in accuracy with the ELISA test version (unified-GP) in diagnosis of AG and Hp in patients referred for diagnostic gastroscopy. Full article

Background: Barrett’s esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic proteinase linked to maintaining normal epithelial morphology, is often absent in advanced gastrointestinal malignancies. This study comprehensively investigates PGC expression across cancers, particularly in esophageal cancer (ESCA), to clarify its role in BE progression to EAC. Methods: We utilized multiple bioinformatic platforms (TIMER, UALCAN, cBioPortal, GEPIA, STRING, Metascape, and GEO database) to assess PGC expression, genomic alterations, and correlations with clinicopathological features, survival, and immune infiltration. Additionally, using the GEO dataset, we compared non-dysplastic Barrett’s esophagus (NDBE) patients with those who progressed to malignancy, identifying differentially expressed genes (DEGs), their interactions, and potential roles in progression. Results: PGC was notably upregulated in various cancers, especially in adjacent normal tissues of ESCA. Genomic amplifications of PGC were linked to improved survival in EAC patients, particularly those with high PGC expression, suggesting a protective role. Moreover, PGC expression positively correlated with favorable immune infiltration, notably B cells and CD8+ T cells. Enrichment analysis of downregulated DEGs revealed significant involvement in key biological processes, specifically in extracellular matrix organization. Among the downregulated DEGs, we identified PGC among the top 10 hub genes, underscoring its role in tissue homeostasis. Conclusions: These findings suggest that PGC could serve as a promising biomarker for predicting the high-risk transformation from BE to EAC, offering new insights into EAC progression and future therapeutic targets. Full article

The role of the yolk sac membrane (YSM) and digestive tract in the processing of egg yolk proteins during embryogenesis is unexplored in the duck Anas platyrhynchos domestica. Here, we investigated in the duck embryo the function of the YSM, proventriculus, and small intestine in protein digestion and uptake. We tested the expression of aminopeptidase N (APN) and the oligopeptide transporter PepT1 as well as the expression of cathepsin B (CTSB) and cathepsin D (CTSD) lysosomal genes in the YSM during incubation days 12, 14, 16–18, 20, 22, 24, 26, and 28 (the day of hatch). Also, we examined embryonic duck pepsinogen (EDPg) expression in the proventriculus and APN and PepT1 expression in the small intestine. In the YSM, CTSD expression was weak compared to that of CTSB, and the expression of CTSB, APN, and PepT1 reached its maximum on day 24 and decreased afterwards. In the proventriculus, EDPg expression peaked on days 17 to 20 and decreased thereafter. The APN and PepT1 expression levels were highest in the jejunum and ileum and reached their maximum on day 28. Our results suggest that the YSM plays a role in the degradation and uptake of the peptides that are digested by the activated yolk proteases, and it also functions in the lysosomal digestion of yolk lipoproteins. Furthermore, the proventriculus is possibly involved in the digestion of yolk proteins. Finally, the jejunum and ileum appear to be the primary sites for peptide digestion and absorption at the end of the incubation. Full article

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients. Full article

Functional dyspepsia is distinguishable from Helicobacter pylori-associated dyspepsia. However, distinguishing H. pylori-associated dyspepsia from functional dyspepsia before H. pylori eradication is difficult. Therefore, in the present study, we aimed to investigate whether serum pepsinogen levels before H. pylori eradication are associated with the amelioration of dyspepsia after successful H. pylori eradication. Additionally, we examined the usefulness of serum pepsinogen levels and other factors in predicting dyspepsia outcomes. H. pylori eradication was effective in 14 patients (Responders) and ineffective in 19 patients (Non-responders). The pepsinogen I/II ratio in Responders (3.4 ± 1.2) and Non-responders (2.3 ± 1.0) differed significantly (p = 0.006). The optimal cut-off pepsinogen I/II value was 2.3. Multivariate logistic regression analysis showed that the adjusted odds ratio for Non-responders was 26.1 (95% confidence interval: 2.0–338.0, p = 0.012) for a pepsinogen I/II ratio ≤ 2.3 and 8.10 (95% confidence interval: 1.1–57.6, p = 0.037) for smoking habits. The pepsinogen I/II ratio and smoking habits were associated with the effects of H. pylori eradication on dyspeptic symptoms. Thus, the pepsinogen I/II ratio cut-off value can be used to identify patients likely to respond to H. pylori eradication after the resolution of dyspeptic symptoms. Full article

Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel^®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. Full article

Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion. Full article

Endoscopy is mandatory to detect early gastric cancer (EGC). When considering the cost-effectiveness of the endoscopic screening of EGC, risk stratification by combining serum pepsinogen values and anti-H. pylori IgG antibody values is very promising. After the detection of suspicious lesions of EGC, a detailed observation using magnifying endoscopy with band-limited light is necessary, which reveals an irregular microsurface and/or an irregular microvascular pattern with demarcation lines in the case of cancerous lesions. Endocytoscopy enables us to make an in vivo histological diagnosis. In terms of the indications for endoscopic resection, the likelihood of lymph node metastasis and technical difficulties in en bloc resection is considered, and they are divided into absolute, expanded, and relative indications. Endoscopic mucosal resection and endoscopic submucosal dissection are the main treatment modalities nowadays. After endoscopic resection, curability is evaluated histologically as endoscopic curability (eCura) A, B, and C (C-1 and C-2). Recent evidence suggests that the outcomes of endoscopic resection for many EGCs are comparable to those of gastrectomy and that endoscopic resection is the gold standard for node-negative early gastric cancers. Personalized medicine is also being developed to overcome the unmet needs in treatments of EGC, for example the further expansion of indications and newer resection techniques, such as full-thickness resection. Full article

Gastritis is an inflammatory process in the gastric mucosa and submucosa caused by Helicobacter pylori (H. pylori). The infection modulates immune components, such as interleukin (IL) 17, high sensitivity C-reactive protein (hsCRP) and pepsinogen. This study aimed to determine the relationship between IL-17, hsCRP and pepsinogen in H. pylori infected gastritis. This observational cross-sectional study was conducted at Prof. Dr. R. D. Kandou General Hospital Manado from May-July 2022. Measurement of blood sample levels of IL-17, hsCRP, pepsinogen I, pepsinogen II and pepsinogen I/II ratio. Spearman’s statistical test was used to determine correlations between these variables. This study involved 48 patients aged 21–64, with a majority of females (67%). IL-7 had a positive correlation with pepsinogen I (r = 0.292; p = 0.044) and pepsinogen II (r = 0.288; p = 0.047) in H. pylori infected gastritis. Meanwhile, IL-17 with pepsinogen I/II ratio, hsCRP with pepsinogen I, pepsinogen II, pepsinogen I/II ratio and IL-17 with hsCRP did not show a significant correlation (p > 0.05). There was a correlation between IL 17 to pepsinogen I and pepsinogen II in gastritis infected with H. pylori, suggesting the importance of these early markers of inflammation in determining the severity of gastric mucosal inflammation in pylori-infected patients. Full article

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host’s responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer. Full article