Gastritis Lesions Research Articles

Endoscopic morphology of gastric MALT lymphoma correlate with API2/MALT1 fusion and predict treatment response after helicobacter pylori eradication

BackgroundThe presence of API2/MALT1 fusion in gastric mucosa-associated lymphoid tissue (MALT) lymphoma predicts poor response to Helicobacter pylori (Hp) eradication therapy. This study aimed to assess the correlation between endoscopic morphology of MALT lymphoma and API2/MALT1 fusion and evaluate treatment response to Hp eradication based on morphological subtypes.MethodsA retrospective review was conducted on patients diagnosed with gastric MALT lymphoma between January 2011 and December 2022. Endoscopic morphology was categorized as superficial, non-superficial, or mixed type. The superficial type was further classified into gastritis superficial lesion and localized superficial lesion based on border clarity. Logistic regression models evaluated the impact of clinical and endoscopic characteristics on anti-Hp therapy effectiveness.ResultsAmong the 114 patients included, 93 (81.6%) were Hp-positive, and API2/MALT1 fusion was detected in 58 (50.9%) cases, The superficial type was the predominate morphology (73/114, 64%). The regular arrangement of collecting venules (RAC) sign was noted in 21 (18.4%) cases. In superficial subtypes, the RAC signs were more frequently observed in localized lesion than gastritis lesion (35.6% vs. 7.1%, p = 0.01). and the superficial localized lesion was more common in individuals with positive API/MALT1 fusion than negative ones (76.9% vs. 44.1%, p = 0.01). Following Hp eradication, the remission rate for localized lesion was 34.3%, significantly lower than for gastritis lesion (66.7%, p = 0.01). Both endoscopic morphology (OR = 0.26, 95% CI 0.09–0.75) and API2-MALT1 fusion (OR = 14.29, 95% CI 4.19–48.67) impacted the efficacy of anti-Hp therapy. However, multivariate analysis identified API2-MALT1 fusion as the only independent predictor of treatment outcome (OR = 12.18, 95% CI 3.49–42.55, p < 0.001).ConclusionGastric MALT lymphomas with superficial-type morphology, particularly those with defined borders resembling early gastric cancer, were associated with API2/MALT1 fusion and a lower remission rate after Hp eradication therapy. This suggests that endoscopic morphology, along with API2/MALT1 fusion status, could help predict the therapeutic response, with API2/MALT1 fusion serving as a critical indicator of treatment resistance.

Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.

Detection of CDH1 gene promoter hypermethylation in gastric cancer and chronic gastritis

AimThe current study aimed to assess the frequency of CDH1 promoter gene hypermethylation in gastric cancer and chronic gastritis and its correlation with clinicopathological aspects. MethodsMethylation-specific PCR was used to detect CDH1 promoter gene hypermethylation in 53 chronic gastritis patients and 40 gastric cancer patients along with normal adjacent tissues. ResultsThe chronic gastritis group comprised 29 males and 24 females with a mean age of 51.8 ± 12.96 years, and 49.1 % of them were positive for H. pylori infection. The frequency of CDH1 hypermethylation in gastritis lesions was 18.8 %. CDH1 hypermethylation showed a significant correlation with H. pylori infection (p = 0.039), but no significant association was observed with other clinical features. The gastric cancer group consisted of individuals with a mean age of 65.4 ± 10.6, among them, 77.5 % were male and 22.5 % were female, 62.5 % had PT3 tumors, 40 % had PN1 lymph node involvement, and the majority (47.5 %) of samples were obtained from body segment. CDH1 hypermethylation was significantly associated with depth of invasion (p = 0.017) and nodal invasion (p = 0.041) in this group. In both groups, normal adjacent specimens lacked CDH1 hypermethylation, and there was no statistically significant correlation between CDH1 hypermethylation and age at which the tumor was diagnosed, gender, activity level, or tumor location. ConclusionThis study demonstrates that E-cadherin methylation is associated with some characteristics of chronic gastritis and gastric cancer. These findings support previous research indicating that CDH1 hypermethylation may play a significant role in the development of gastric cancer.

Reliability of RUT done on endoscopy guided gastric biopsy in detecting Helicobactor Pylori

Introduction: This study was done to identify the reliability of RUT in detecting H. Pylori in patients of gastritis by performing Histopathological examination. Endoscopic biopsy samples were taken from gastritis lesions present in the stomach. Methods: This was a prospective observational study done at Jawaharlal Nehru Medical College (JNMC), Aligarh Muslim University (AMU), Aligarh between May 2021 and May 2022 with a sample size of 230 patients. The endoscopists performed RUT on biopsy samples taken from gastritis lesions and sent another biopsy sample from the same patient for histopathological examination. On the basis of histopathological report, results were compared and analyzed. Results: In our study the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of RUT were 60.81%, 67.31% ,78.36%, 46.88% , and 65.22%, respectively. Conclusion: Our study suggests that RUT can reliably identify Helicobacter pylori infection in gastric mucosa.

Detection of vacA gene alleles frequency in Helicobacter pylori strains from patients with gastric diseases in Zliten city Libya

Helicobacter pylori (H. pylori) has worldwide distribution, leading to various gastric diseases, including chronic gastritis, peptic ulcer and gastric cancer. A vacA gene, which encodes a vacuolating cytotoxin is one of the most known virulence gene of the bacterium. The aim of this study was to evaluate the most common vacA alleles (s1 and s2) in H. pylori strains isolated from Libyan patients and its relationship with ages and gastritis lesions. Gastric biopsies were obtained from patients for DNA extraction. vacA genotypes were analyzed by PCR and agarose electrophoresis. s1 and s2 genotypes were also confirmed by DNA sequencing. The allele s2 occurred in 81% of the all examined group, which represent the most frequently observed of the signal encoding region. Whereas s1 genotype had the lowest frequency 19%. Statistically significant differences in s1 and s2 alleles in relation to a ages were not detected. This study showed that there was a relationship between the presence of vacA gene and progression of gastritis. the predominant vacA gene alleles in Zliten city is s2 allele.

Detection and quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus-6 in stomach frozen tissue of chronic gastritis and gastric cancer patients.

Human herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the Epstein-Barr virus (EBV) and gastric cancer (GC) has been established, the role of the viruses in various stomach diseases remains unknown. The frequencies and viral copy number of EBV, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) among 50 gastric cancer tumors and 105 chronic gastritis tissues were measured by quantitative real-time PCR. In the tumor specimens and the adjacent normal tissues EBV was found in 60% and 30.9%, CMV in 14% and 4.7%, and HHV-6 in 18%, and 14.2%, respectively. The detection rate of EBV and CMV was found to be significantly higher in tumor tissues relative to the adjacent normal tissues. Also, in chronic gastritis, the frequency of EBV, CMV, and HHV-6 was 19%, 12.3%, and 15.2%, respectively, compared with 16.4%, 1.1%, and 8.2% in their corresponding normal tissues. Here, the CMV frequency was found to be significantly higher in gastritis tissues relative to the adjacent normal tissues. Furthermore, viral load in both gastric cancer and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between gastric cancer with both EBV and CMV. Meanwhile, analyses revealed a strong association between the EBV, CMV, and HHV-6 viral loads with gastritis (P = 0.0026, P < 0.0001, and P = 0.0405, respectively). Our results suggest that these three viruses might contribute to the induction and development the gastritis and gastric cancer.

Gastrin-17 Levels in Pre-malignancy Gastritis Lesions

Background: Gastritis is an inflammatory process on the lining of the stomach that could be caused by various factors. Untreated inflammatory processes could lead to ulcers. Gastrin hormone is released by gastrin-secreting enteroendocrine cells (G cells) in the stomach, which influence the secretion of gastric acid and helps the proliferation of gastric epithelial cells. Its abnormal secretion in H. pylori infection, with food-stimulated excessive release of gastrin, is the most prominent abnormality. One concern is the relationship of excess gastrin secretion to the incidence of gastric cancer. This study aimed to show the difference in gastrin levels on patients with gastritis, both with and without pre-malignant lesions. Methods: This research was a cross-sectional study with 40 samples that had met the inclusion and exclusion criteria. Endoscopy was performed to assess the gastric mucosa and tissue biopsy was performed afterward. The data was analysed in univariate and bivariate ways. Results: From this study, 20 people were positive for pre-malignant lesions (50%). Mann–Whitney test analysis was used to analyse the data and showed there was a significant difference between gastrin levels on patients with gastritis with and without pre-malignant lesions, with a p value of 0.01. Conclusion: There is a significant difference between gastrin levels in patients with gastritis with and without pre-malignant lesions, which could be the basis for early detection of patients with gastric cancer.

Diagnostic Value of Serum Pepsinogen Levels for Screening Gastric Cancer and Atrophic Gastritis in Asymptomatic Individuals: A Cross-Sectional Study

BackgroundPepsinogens (PGs) can be used for gastric cancer (GC) screening, but the cutoff levels vary among studies, and PG levels are influenced by numerous factors. The aim of this article is to examine the diagnostic value of PG levels and Helicobacter pylori (Hp) status for GC and atrophic gastritis screening in asymptomatic individuals undergoing health checkup in China.Patients and MethodsThis was a multicenter cross-sectional study of subjects who underwent health checkup from 10/2016 to 10/2018 at nine International Healthcare Centers in China. All participants underwent gastroscopy and pathological examination, serum PG, 13C-urea breath test, and/or Hp serological current infection marker rapid test, all on the same day. PG-related parameters were analyzed in different Hp subgroups and regions.ResultsThe patients were grouped as non-atrophic (NAG, n = 1,590), mild to moderate atrophic (MAG, n = 273), severe atrophic (SAG, n = 49), and GC (n = 10). The serum PG levels in these groups decreased with increasing pathological severity. In the same pathological groups, PGI and PGII levels were higher in the Hp-positive subgroup, while PGR (PGI/PGII ratio) was lower (P < 0.05). The best cutoff values for atrophy diagnosis were PGI ≤73.1 ng/ml and PGR ≤9.8, for severe atrophy were PGI ≤63.9 ng/ml and PGR ≤9.09, and for GC was PGR ≤4.7 (all P < 0.05 and area under the curve >0.7). The cutoff points varied with Hp status and China regions.ConclusionSerum PG levels might be used for the screening of gastric atrophic gastritis lesions. The results suggest that different cutoff values should possibly be used in different Hp status groups and geographical regions, but it will have to be validated in future studies. Future studies should also examine the value of PG levels for GC detection.

Gastric cancer – histopathological correlations between tumor and non-tumor gastric mucosa changes

Gastric cancer is a widely geographically distributed malignancy with high prevalence, therefore being a serious health problem that needs standardized methods for early diagnosis and treatment. The aim of the study was to evaluate the correlation of some epidemiological and clinical data with the histological features. The study group was made up of 66 patients that underwent surgical removal of the gastric neoplasm, and the pathological exam showed the morphological features of the tumor, as well as the ones of the unaffected mucosal tissue. Topographically, the highest incidence of the tumor was registered in the gastric antrum, but in recent years, an increased incidence of the superior gastric pole localization was recorded. The macroscopic aspects reveal that the ulcerated type 2 Borrmann is the most frequent, and alongside type 3 Borrmann, the ulcer-infiltrative type represents most of the gastric antrum cancers. The analysis of the tumor invasion showed that most carcinomas underwent surgery when the tumor invaded the serosa (pT3) or even the perigastric tissues (pT4). In our research, we chose Goseki’s microscopic classification because of its best coverage of the histological heterogeneity of the gastric carcinomas, providing information about the percentage of the cellular and secretory differentiation with direct impact on the invasion of the tumor. In more than 70% of the cases, the patients showed lesions of severe chronic atrophic gastritis of the non-tumor mucosa. Lately, the incidence of Helicobacter pylori has been 5.5%, lower than indicated by mainstream literature. We observed that the incidence of type 3 incomplete intestinal metaplasia, as the most commonly involved factor in the etiopathogenesis of gastric neoplasms, was encountered in 36.3% of the cases, this percentage rising proportionally with age and being frequently associated with antrum tumors. In conclusion, the permanent analysis of the relation between epidemiological data and some histological features might be relevant for the characterization of the tumoral process or the non-tumor gastric mucosa, leading to an evaluation of the prognosis.

Expert-level classification of gastritis by endoscopy using deep learning: a multicenter diagnostic trial.

Abstract Background and study aims Endoscopy plays a crucial role in diagnosis of gastritis. Endoscopists have low accuracy in diagnosing atrophic gastritis with white-light endoscopy (WLE). High-risk factors (such as atrophic gastritis [AG]) for carcinogenesis demand early detection. Deep learning (DL)-based gastritis classification with WLE rarely has been reported. We built a system for improving the accuracy of diagnosis of AG with WLE to assist with this common gastritis diagnosis and help lessen endoscopist fatigue. Methods We collected a total of 8141 endoscopic images of common gastritis, other gastritis, and non-gastritis in 4587 cases and built a DL -based system constructed with UNet + + and Resnet-50. A system was developed to sort common gastritis images layer by layer: The first layer included non-gastritis/common gastritis/other gastritis, the second layer contained AG/non-atrophic gastritis, and the third layer included atrophy/intestinal metaplasia and erosion/hemorrhage. The convolutional neural networks were tested with three separate test sets. Results Rates of accuracy for classifying non-atrophic gastritis/AG, atrophy/intestinal metaplasia, and erosion/hemorrhage were 88.78 %, 87.40 %, and 93.67 % in internal test set, 91.23 %, 85.81 %, and 92.70 % in the external test set ,and 95.00 %, 92.86 %, and 94.74 % in the video set, respectively. The hit ratio with the segmentation model was 99.29 %. The accuracy for detection of non-gastritis/common gastritis/other gastritis was 93.6 %. Conclusions The system had decent specificity and accuracy in classification of gastritis lesions. DL has great potential in WLE gastritis classification for assisting with achieving accurate diagnoses after endoscopic procedures.

Modified Banxia Xiexin decoction for treatment of precancerous lesions of atrophic gastritis: Efficacy and influence on TGF -β1/Smads signaling pathway

Modified Banxia Xiexin decoction for treatment of precancerous lesions of atrophic gastritis: Efficacy and influence on TGF -β1/Smads signaling pathway

Programmed Death Ligand 1-Expressing Classical Dendritic Cells MitigateHelicobacter-Induced Gastritis.

Background & AimsHelicobacter pylori has been reported to modulate local immune responses to colonize persistently in gastric mucosa. Although the induced expression of programmed cell death ligand 1 (PD-L1) has been suggested as an immune modulatory mechanism for persistent infection of H pylori, the main immune cells expressing PD-L1 and their functions in Helicobacter-induced gastritis still remain to be elucidated.MethodsThe blockades of PD-L1 with antibody or PD-L1–deficient bone marrow transplantation were performed in Helicobacter-infected mice. The main immune cells expressing PD-L1 in Helicobacter-infected stomach were determined by flow cytometry and immunofluorescence staining. Helicobacter felis or H pylori–infected dendritic cell (DC)-deficient mouse models including Flt3–/–, Zbtb46–diphtheria toxin receptor, and BDCA2–diphtheria toxin receptor mice were analyzed for pathologic changes and colonization levels. Finally, the location of PD-L1–expressing DCs and the correlation with H pylori infection were analyzed in human gastric tissues using multiplexed immunohistochemistry.ResultsGenetic or antibody-mediated blockade of PD-L1 aggravated Helicobacter-induced gastritis with mucosal metaplasia. Gastric classical DCs expressed considerably higher levels of PD-L1 than other immune cells and co-localized with T cells in gastritis lesions from Helicobacter-infected mice and human beings. H felis– or H pylori–infected Flt3–/– or classical DC-depleted mice showed aggravated gastritis with severe T-cell and neutrophil accumulation with low bacterial loads compared with that in control mice. Finally, PD-L1–expressing DCs were co-localized with T cells and showed a positive correlation with H pylori infection in human subjects.ConclusionsThe PD-1/PD-L1 pathway may be responsible for the immune modulatory function of gastric DCs that protects the gastric mucosa from Helicobacter-induced inflammation, but allows persistent Helicobacter colonization.

Predictive Value of CDX2 and SOX2 in Chronic Gastritis and Intestinal-type Gastric Cancer

BACKGROUND: Worldwide gastric cancer (GC) ranks sixth in incidence and second in mortality among all malignancies. CDX2 has an essential role in the development and maintenance of intestinal differentiation in the gut and ectopic sites such as intestinal metaplasia (IM) of the stomach. SOX2 contributes to the cell lineages normally found in the stomach, suggesting contribution in gastric differentiation. AIM: The aim of the study was to assess the expression of CDX2 and SOX2 in chronic gastritis (CG) lesions associated with Helicobacter pylori, IM, or dysplasia as well as in intestinal-type GC. METHODS: Immunohistochemical staining for CDX2 and SOX2 were applied on archival paraffin blocks from 80 CG cases, 40 intestinal-type GC cases, and 10 controls. CG cases were either of non-specific inflammation or associated with H. pylori infection. GC cases were of intestinal-type only, excluding any other type of GC. Control cases were of minimal gastritis, negative for H. pylori, IM, and dysplasia. RESULTS: CDX2 expression was correlated with CG associated with H. pylori, IM, and dysplasia as well as with more differentiated and less invasive pattern of intestinal-type GC, while SOX2 expression was correlated with CG negative for H. pylori and IM as well as with less differentiated and more invasive intestinal-type GC. CONCLUSION: Both CDX2 and SOX2 could predict the behavior of CG disease over time and plan the suitable line of treatment and both proteins could be potential targets for novel therapeutic interventions.

Pullulation bactérienne gastrique : une observation histologique inhabituelle, à ne pas méconnaître

Gastric bacterial overgrowth is a rare situation, which may be associated with short- and long-term complications. It must be known from pathologists, since it might be detected incidentally at histological examination of gastric biopsies. We report here the case of a 74-year old woman, obese, without significant medical history, apart from a gastro-esophageal reflux treated by the long-term administration of proton pump inhibitors (PPI). In this patient, gastric bacterial overgrowth was detected at histological examination of gastric biopsies performed after colectomy for left colon adenocarcinoma. Large clusters of small, round, "coccoid" bacteria were present in the gastric mucus. Their characteristics were suggestive of enterobacteria. Bacterial proliferation was associated with severe and diffuse lesions of active gastritis. The course was rapidly unfavorable, and the patient rapidly deceased with multiple infections and multi-organ failure. In our observation, the pathogenesis of gastric bacterial overgrowth was probably multifactorial. It might have been facilitated by long-term PPI treatment and obesity, which are known risk factors, and promoted, in the post-operative setting, by multiple infections and immune failure. Our observation underlines that gastric bacterial overgrowth might be associated with severe gastritis, which might justify antibiotherapy. Other consequences of prolonged gastric dysbiosis cannot be excluded, such as the promotion of neoplastic lesions.

Multispectral imaging detects gastritis consistently in mouse model and in humans

Gastritis constitutes the initial step of the gastric carcinogenesis process. Gastritis diagnosis is based on histological examination of biopsies. Non-invasive real-time methods to detect mucosal inflammation are needed. Tissue optical properties modify reemitted light, i.e. the proportion of light that is emitted by a tissue after stimulation by a light flux. Analysis of light reemitted by gastric tissue could predict the inflammatory state. The aim of our study was to investigate a potential association between reemitted light and gastric tissue inflammation. We used two models and three multispectral analysis methods available on the marketplace. We used a mouse model of Helicobacter pylori infection and included patients undergoing gastric endoscopy. In mice, the reemitted light was measured using a spectrometer and a multispectral camera. We also exposed patient’s gastric mucosa to specific wavelengths and analyzed reemitted light. In both mouse model and humans, modifications of reemitted light were observed around 560 nm, 600 nm and 640 nm, associated with the presence of gastritis lesions. These results pave the way for the development of improved endoscopes in order to detect real-time gastritis without the need of biopsies. This would allow a better prevention of gastric cancer alongside with cost efficient endoscopies.

P0932CLINICAL EVALUATION OF DISTURBANCES GASTROINTESTINAL TRACT IN PATIENT WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic kidney disease (CKD) affects gastrointestinal function and results in numerous adaptive and maladaptive responses. Disruption of the colonic microbiome and its attendant consequences - the loss of gut barrier integrity and increased generation of uremic toxins - has become well-recognized. However, less attention has been paid to characterizing the mechanisms behind the dysfunction of the upper gastrointestinal (GI) tract, largely owing to the difficulty of studying small bowel function in vivo Method The study included 72 people, of whom 52 made up the main group (CKD group) and 20 people - the comparison group (healthy volunteers without a kidney and cardiovascular disease). The main group consisted of patients with CKD stage 3 (RCGF creatinine 30-59ml / min / m2). The criterion for the inclusion of patients in the study, in addition to reducing the eGFR (estimated glomerular filtration rate), was the presence of arterial hypertension. The renal filtration function was the preserved comparison group and was reduced in the CKD group (p &amp;lt;0.001), which served as a criterion for the inclusion of patients in the study. To assess the state of the gastrointestinal tract, all patients underwent an endoscopic study with an assessment of the acidity and evacuation function of the stomach Results The study showed that 75% of patients had complaints of a dry and unpleasant taste in the mouth, poor appetite, aversion to meat food, nausea. These symptoms were directly related to the level of eGFR. There was also a difference in the frequency and nature of the erosive, erosive-ulcerative, ulcerative lesions of the esophagus and formation of erosions and ulcers in patients with CKD occurred significantly more often against the background of chronic gastritis and with the severity of the inflammatory process with severe dyspeptic disorders. The frequency of erosive, erosive-ulcerative and ulcerative lesions of the mucous membrane of the upper GI tract among CKD patients was 72%, which were manifested by nausea, decreased appetite, heaviness in the stomach after eating, belching, heartburn, epigastric pain (in 50% of patients), meteorism, pain in the epigastric region during palpation. Endoscopic examination of patients with CKD noted the presence of erosive esophagitis, erosive gastritis, erosive bulb it, erosive duodenitis, mixed erosive lesions, erosive-ulcerative gastritis, gastric ulcer, ulcer of duodenal ulcer. Among them, the leading place is occupied by erosive gastritis and mixed erosive lesions, which account for 22% and 27%, respectively. Hemorrhagic erosions were more common in the stomach (41%) and 12: duodenal ulcer (47%) in patients with CKD Conclusion Erosive, erosive-ulcerative, ulcerative lesions of the upper gastrointestinal tract occur in 76% of patients with CKD. The frequency, nature, prevalence of these lesions are associated with the treatment of CKD - active (hemodialysis) and conservative, the stage of chronic renal failure. In patients with chronic renal failure, the endoscopic picture of erosive, erosive-ulcerative, ulcerative lesions of the upper GI tract is diverse.

基于健脾为本治疗慢性萎缩性胃炎及癌前病变的研究

基于健脾为本治疗慢性萎缩性胃炎及癌前病变的研究

Activation of FXR promotes intestinal metaplasia of gastric cells via SHP‑dependent upregulation of the expression of CDX2

Gastric intestinal metaplasia (IM) induced by bile acid is a precancerous lesion of gastric adenocarcinoma and is associated with the expression of caudal-related homeobox 2 (CDX2). In the present study, the role of farnesoid X receptor (FXR) on the regulation of CDX2 in gastric cells was investigated and the underlying molecular mechanisms were examined. Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. Cells were treated with CDCA in the presence or absence of the FXR antagonist or FXR siRNA transfection. Next, cells were treated with CDCA in the presence or absence of SHP siRNA transfection and FXR, CDX2 and SHP mRNA and protein levels were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. A chromatin immunoprecipitation assay was performed to examine the relationship between FXR and SHP and the expressions of FXR and CDX2 in gastritis and IM tissues were detected using immunohistochemistry. The results revealed that CDCA was able to induce CDX2 expression, which could be blocked by inhibition or knockdown of FXR. Mechanistically, FXR directly induced the expression of small heterodimer partner (SHP). SHP knockdown significantly decreased CDCA-induced CDX2 expression. ChIP results indicated that FXR could directly bind SHP promoter and promote SHP expression. Finally, immunohistochemistry results demonstrated that the expression levels of CDX2 and FXR in human IM lesions were significantly higher, compared with those in gastritis lesions, and were positively correlated. Collectively, these results revealed that the activation of FXR and sequential direct transcriptional induction of SHP were involved in the expression of CDX2 induced by bile acid in gastric IM lesions.

Species-specific role of gene-adjacent retroelements in human and mouse gastric carcinogenesis.

Helicobacter pylori (HP) infection promotes the recruitment of bone marrow stem cells into chronic gastritis lesions. Some of these marrow stem cells can differentiate into gastric epithelial cells and neoplastic cells. We propose that HP-associated methylation could stabilize trans-differentiation of marrow-derived stem cells and that an unstable methylation status is associated with a risk of gastric cancer. Pathobiologic behavior of experimental mouse gastric cancer is mild compared to invasive and metastatic human gastric cancer. Differences in epigenetic stabilization of adult cell phenotypes between humans and mice could provide a foundation to explore the development of invasive and metastatic gastric cancer. Retroelements are highly repetitive sequences that play an essential role in the generation of species diversity. In this review, we analyzed retroelements adjacent to human and mouse housekeeping genes and proposed a possible epigenetic mechanism for HP-associated carcinogenesis.

Identification of circulating microRNAs for the diagnosis of early-stage gastric cancer.

33 Background: The development of gastric cancer (GC) is a stepwise progression from non-active gastritis (NAG), chronic active gastritis (CAG) and precursor lesions of GC (PLGC: atrophy, metaplasia). Early detection of GC improves survival rates. Recent evidence has proposed circulating microRNAs (c-miRNAs) as biomarkers. The aim was to explore the c-miRNA profile of a cohort of non-GC and GC patients in order to identify early biomarkers of GC. Methods: Thirty-eight patients were enrolled: ten with NAG, nine with H. pylori infected with CAG, eight with PLGC, and ten with GC. GC patients were at TNM stages I and II. As quality controls, synthetic RNA was added during the isolation, cDNA synthesis, and PCR steps. MiRNA profiling was performed using Exiqon Human Panel I. Exploratory significance was set at P&lt;0.05 with fold change (FC)≥1.6. Results: Of the total of 372 miRNAs analyzed, 154 miRNAs were detected in all samples. miR-185-5p was used to normalize. Compared to NAG individuals, GC patients showed downregulation of three miRNAs. GC patients also showed reduced expression of miR-205 compared to H.pylori-infected patients with CAG. Five miRNAs were upregulated in GC patients compared to PLGC patients (miR-134, miR-204, miR-224, miR-409, miR-877). Finally, in comparison with non-GC, seven miRNAs were found to be deregulated in GC patients (miR-130b, miR-144, miR-205, miR-219a, miR-224, miR-451a, miR-501). Specificities calculated at 90% sensitivity were low and significant FC ranged from -3.2 to 2.8. Conclusions: Using miRNA qPCR quantification, we found a deregulation of c-miRNAs in early GC. However, our results also show low diagnostic accuracy for early GC due to the small FC observed and the overlap in the miRNA levels between non-GC and GC patients. Further validation in a larger cohort and a prospective study is needed to determine conclusively whether these miRNAs serve as biomarkers. In our opinion, new methods need to be developed in order to quantify c-miRNAs and improve their diagnostic accuracy. [Table: see text]