Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa.

In vivo administration of dopamine (DA) receptor (DR)-related drugs modulate gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R-/- mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R-/- mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R-/- mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.

Risk stratification for gastric cancer after Helicobacter pylori eradication: A population-based study on Matsu Islands.

BACKGROUND AND AIM: The reliable method to stratify the gastric cancer risk after Helicobacter pylori eradication remains an elusive goal. METHODS: Mass eradication of H. pylori began in 2004 in a high-risk population. After eradication, a screening program involving first-stage serological tests (pepsinogen-I, pepsinogen-II, H. pylori immunoglobin G, and gastrin-17) and second-stage endoscopic examination was launched in 2015-2018. Index lesions included gastric cancer or extensive premalignant lesions. We evaluated the performance of the serological tests to "rule in" and "rule out" the risk based on positive and negative likelihood ratios, respectively. The methylation levels of microRNA-124a-3 in the stomach were measured to indicate genetic damage. RESULTS: Among 6512 invited subjects, 3895 (59.6%) participated. Both gastrin-17 and pepsinogen tests were normal in 3560 (91.4%) subjects; 206 (5.3%) gastrin-17 and 129 (3.3%) pepsinogen tests were abnormal. Years after eradication, the severity of gastritis had fallen greatly, and extensive premalignant lesions or gastric cancer frequently occurred in newly non-atrophic-appearing mucosa. Pepsinogen testing could moderately predict atrophic gastritis (positive likelihood ratio: 4.11 [95% confidence interval: 2.92-5.77]; negative likelihood ratio: 0.14 [0.10-0.19]). Gastrin-17 was not useful (0.66 and 1.20, respectively). However, pepsinogen testing poorly predicted the index lesions (2.04 [1.21-3.42] and 0.57 [0.34-0.95]). DNA methylation levels in the post-eradication mucosa were more discriminative for predicting index lesions (3.89 [2.32-6.54] and 0.25 [0.15-0.42]). CONCLUSIONS: After eradication, pepsinogen false-negative results become more frequent because histology is improved but genetic damage may persist. Direct testing for genetic damage offers better discrimination.

Human gastric cancer risk screening: From rat pepsinogen studies to the ABC method.

We examined the development of gastric cancer risk screening, from rat pepsinogen studies in an experimental rat gastric carcinogenesis model induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and human pepsinogen studies in the 1970s and 1980s to the recent "ABC method" for human gastric cancer risk screening. First, decreased expression or absence of a major pepsinogen isozyme, PG1, was observed in the rat gastric mucosa from the early stages of gastric carcinogenesis to adenocarcinomas following treatment with MNNG. In the 1980s, decreases in PGI in the human gastric mucosa and serum were identified as markers of atrophic gastritis. In the 1990s, other researchers revealed that chronic infection with Helicobacter pylori (Hp) causes atrophic gastritis and later gastric cancer. In the 2000s, a gastric cancer risk screening method combining assays to detect serum anti-Hp IgG antibody and serum PGI and PGII levels, the "ABC method", was established. Eradication of Hp and endoscopic follow-up examination after the ABC method are recommended to prevent gastric cancer.

Presence of Gastric Pepsinogen in the Trachea Is Associated with Altered Inflammation and Microbial Composition.

Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.

Endoscopic and Pathological Characteristics of Helicobacter pylori Infection-Negative Early Gastric Cancer.

BACKGROUND: The characteristics of Helicobacter pylori (HP) infection-negative gastric cancer (HPINGC) have not been well documented because of the rareness. The aim of this study was to classify HPINGC endoscopically and clinicopathologically. METHODS: This retrospective study included 1,741 early gastric cancer lesions and evaluated their HP infection status. Expression levels of MUC5AC, MUC6, MUC2, CD10, p53, MIB-1, pepsinogen-I, H+/K+ ATPase, chromogranin A, E-cadherin, and gastrin were evaluated in tumors by immunohistochemistry (IHC). RESULTS: Among the analyzed lesions, 19 (1.1%) were diagnosed as HPINGC and classified into 6 types: undifferentiated (5 lesions), fundic gland (2 lesions), cardiac gland (1 lesion), pyloric gland (3 lesions), foveolar (5 lesions), and mixed (3 lesions) types. Undifferentiated lesions were of pale color, with unclear demarcation and decreased E-cadherin expression. Fundic-type lesions were tan to reddish in color, with submucosal tumor-like protrusions, and positive for pepsinogen-I and H+/K+ ATPase. The cardiac gland type was located in the gastroesophageal junction and was positive for MUC6 and pepsinogen-I. Pyloric gland-type lesions were of the same color as normal mucosa, with mild elevation and unclear demarcation, likely positive for CD10 and chromogranin A. Foveolar epithelial-type lesions were white and elevated, with defined demarcation, and contained MUC5AC-positive cells. Mixed-type lesions, showing various staining patterns in IHC, had both elevated and depressed shape and reddish color. CONCLUSION: Endoscopic observation and IHC were useful for classifying the characteristics of HPINGC, which may preserve the characteristics of its region of origin.

Effect of different salinities on gene expression and activity of digestive enzymes in the thick-lipped grey mullet (Chelon labrosus).

The effects of different environmental salinities (0, 12, 40, and 55 ppt) on pepsinogen 2 (pga2), trypsinogen 2 (try2), chymotrypsinogen (ctr), and pancreatic alpha-amylase (amy2a) gene expression, and on the total activities of their corresponding enzymes, were assessed in Chelon labrosus juveniles, after their corresponding full-complementary DNA sequences were cloned. Furthermore, the quantitative effect of different salinities on the hydrolysis of feed protein by fish digestive enzymes was evaluated using an in vitro system. Relative pga2 expression levels were significantly higher in animals maintained at 12 ppt, while a significantly higher gene expression level for ctr and try2 was observed at 40 ppt. amy2a gene expression showed its maximum level at 40 ppt and the lowest at 55 ppt. A significant reduction in the activity of amylase with the increase in salinity was observed, whereas the maximum activity for alkaline proteases was observed in individuals maintained at 40 ppt. A negative effect of high salinity on the action of proteases was confirmed by the in vitro assay, indicating a decreased efficiency in the digestive function in C. labrosus when maintained at high environmental salinities. Nevertheless, individuals can live under different environmental salinities, even though gene expression is different and the enzymatic activities are not maintained at the highest studied salinity. Therefore, compensatory mechanisms should be in place. Results are discussed on the light of the importance as a new species for aquaculture.

Associations of Helicobacter pylori infection and chronic atrophic gastritis with accelerated epigenetic ageing in older adults.

BACKGROUND: Helicobacter pylori (HP) infection and chronic atrophic gastritis (CAG) have shown strong associations with the development of gastric cancer. This study aimed to examine whether both risk factors are associated with accelerated epigenetic ageing, as determined by the 'DNA methylation age', in a population-based study of older adults (n=1477). METHODS: Serological measurements of HP antibodies and pepsinogen I and II for CAG definition were obtained by ELISA kits. Whole blood DNA methylation profiles were measured by Illumina Human Methylation450K Beadchip. DNA methylation ages were calculated by two algorithms proposed by Horvath and Hannum et al. RESULTS: After adjusting for potential covariates in linear regression models, we found that HP infection, infection with virulent HP strains (CagA+) and severe CAG were significantly associated with an increase in DNA methylation age by ∼0.4, 0.6 and 1 year (all P-values <0.05), respectively. CONCLUSIONS: Our study indicates that both CagA+ HP infection and CAG go along with accelerated epigenetic ageing.

The applicability of ELISA detection of gastric mucosa-expressing proteins for the identification of vomit.

The identification of vomit stains may be helpful for crime scene reconstruction. However, there is no specific and convenient method for identifying vomit stain. Therefore, to establish the procedure for forensic identification of vomit stains, we focused on four gastric mucosa-expressing proteins, pepsinogen I (PGA), pepsinogen II (PGC), gastrin (GAST), and mucin 5AC (MUC5AC). We developed enzyme-linked immunosorbent assay (ELISA) procedures for the detection of these four candidate proteins. The specificity and sensitivity of ELISA detection of these proteins were analyzed, and applicability for the identification of vomit in forensic casework samples was also investigated. We found the sensitivities of ELISA for detection of PGA, PGC, GAST, and MUC5AC from the standard protein (peptide) and from diluted gastric mucosa extract were 10.0-100.0 ng/ml and 1:200-1:1600, respectively. PGA and PGC were successfully detected in stomach contents and gastric mucosa samples; however, these also cross-reacted with some urine and semen samples, respectively, because of low level expression in these fluids. MUC5AC was positive for most gastric mucosa samples; however, it was difficult to detect in stomach contents. ELISA detection of GAST was not suitable for the identification of vomit. All aged samples stored up to 90 days gave positive results for ELISA procedures for PGA, PGC, and MUC5AC. Therefore, ELISA detection of these proteins might be applicable to aged samples. PGA was also detected in all actual vomit samples tested. These results suggest that ELISA for the detection of gastric mucosa-expressing proteins, especially PGA, could be an effective tool for the forensic identification of vomit.

Understanding the mechanism of prosegment-catalyzed folding by solution NMR spectroscopy.

Multidomain protein folding is often more complex than a two-state process, which leads to the spontaneous folding of the native state. Pepsin, a zymogen-derived enzyme, without its prosegment (PS), is irreversibly denatured and folds to a thermodynamically stable, non-native conformation, termed refolded pepsin, which is separated from native pepsin by a large activation barrier. While it is known that PS binds refolded pepsin and catalyzes its conversion to the native form, little structural details are known regarding this conversion. In this study, solution NMR was used to elucidate the PS-catalyzed folding mechanism by examining the key equilibrium states, e.g. native and refolded pepsin, both in the free and PS-bound states, and pepsinogen, the zymogen form of pepsin. Refolded pepsin was found to be partially structured and lacked the correct domain-domain structure and active-site cleft formed in the native state. Analysis of chemical shift data revealed that upon PS binding refolded pepsin folds into a state more similar to that of pepsinogen than to native pepsin. Comparison of pepsin folding by wild-type and mutant PSs, including a double mutant PS, indicated that hydrophobic interactions between residues of prosegment and refolded pepsin lower the folding activation barrier. A mechanism is proposed for the binding of PS to refolded pepsin and how the formation of the native structure is mediated.

Motilin stimulates pepsinogen secretion in Suncus murinus.

Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in suncus.

Chicken and rabbit antibodies against porcine pepsinogen A.

Isolated porcine pepsinogen A was used for the preparation of polyclonal rabbit and polyclonal chicken anti-pepsinogen A antibodies. Immunochemical properties of both immunoglobulin fractions were compared. The rabbit anti-serum was further purified using immobilized porcine pepsinogen A on magnetic cellulose beads and the resulting anti-pepsinogen A fraction proved to be applicable for the separation and the determination of porcine pepsinogen A. In contrary, antibodies prepared from chicken eggs by the same way have been found not suitable for the evaluation of the pepsinogen A level. Unexpectedly, the pre-immune fraction of chicken antibodies showed reactivity against porcine pepsinogen A and the affinity separation of specific polyclonal chicken anti-pepsinogen A antibodies on immobilized porcine pepsinogen A did not result in an enrichment of anti-pepsinogen A antibodies.

Expression pattern and cellular localization of pepsinogen in early development and induced by different diets in the spotted knifejaw (Oplegnathus punctatus).

To solve the high mortality rate of early-stage larval feed conversion during aquaculture in Oplegnathus punctatus, the investigation of the structural and functional characteristics of the gastric tissue was conducted. Histological results showed that the gastric gland rudiment appeared at 17 dph. The basic structure of the stomach was fully developed between 26 and 35 dph. Two pepsinogen genes, named OpPGA1 and OpPGA2, were identified in the spotted knifejaw genome. qPCR results of developmental period showed that the two genes were low in expression during early development (5 and 15 dph). At 20 dph, the two genes started to show trace expression, and at 30 dph the mRNA expression levels of OpPGA1 and OpPGA2 reached the highest levels. Results of pepsin activity detection during the development period showed lower activity was detected 22 dph, followed by a peak at 30 dph. Under different feeding inductions, OpPGA1 showed the highest expression in the basic diet group and hard-shell group, while the expression level in the phytophagous group remained consistently low. The mRNA expression level of OpPGA2 in the phytophagous group was significantly higher than in other groups. Enzyme activity determination under different feeding inductions showed slightly higher enzyme activity in the basic diet group and crustacean group. The results of in situ hybridization showed that the mRNA of both OpPGA1 and OpPGA2 genes was both expressed in gastric gland cells. These information can contribute to the development of practical feeding methods in terms of digestive physiology for the development of larvae.

Iron-deficiency anaemia, gastric hyperplasia, and elevated gastrin levels due to potassium channel dysfunction in the Jervell and Lange-Nielsen Syndrome.

AIM: We investigated extra-cardiac clinical symptoms and signs in the rare Jervell and Lange-Nielsen Syndrome, characterised by impaired KCNQ1 function, a gene essential for gastric acid secretion. METHODS: All Swedish Jervell and Lange-Nielsen cases with double KCNQ1 mutations (14 cases) were investigated by medical record review, an interview, and were offered laboratory testing for iron-deficiency anaemia and gastrointestinal markers. RESULTS: A history of iron-deficiency anaemia in 12 of 14 patients and subjective gastrointestinal symptoms in 13 of 14 patients was revealed. Previous endoscopy in five cases had revealed no case of coeliac or inflammatory bowel disease but three cases of mucosal hyperplasia/dysplasia. Current signs of anaemia or iron substitution were present in 9 of 12 tested cases. Elevated levels of gastrin in seven of nine cases, pepsinogen in six of seven cases, and faecal calprotectin in nine of nine cases were present. A significant correlation between elevated gastrin levels and concurrent iron-deficiency and/or anaemia was revealed (p-value 0.039). CONCLUSIONS: A high frequency of extra-cardiac clinical symptoms and previous medical investigations was found. We propose that the Jervell and Lange-Nielsen Syndrome phenotypically includes gastrointestinal symptoms/signs and secondary iron-deficiency anaemia owing to hypochlorhydria on the basis of KCNQ1 mutations. The resultant elevated gastrin level is a potential risk factor for later gastrointestinal cancer. Clinical monitoring with regard to developing anaemia and hypergastrinaemia should be considered in the Jervell and Lange-Nielsen Syndrome.

Effects of polymorphisms in pepsinogen (PEP), amylase (AMY) and trypsin (TRY) genes on food habit domestication traits in mandarin fish.

Mandarin fish (Siniperca chuatsi) have a peculiar feeding habit of only accepting live fish prey and refusing dead prey and artificial diets. However, previous research has shown that some individuals accept dead prey after gradual domestication. Digestive enzymes are correlated with feeding habits in fish. In the current study, SNPs in the mandarin fish genes for pepsinogen (PEP), amylase (AMY), and trypsin (TRY) were evaluated for associations with feeding habits in domesticated mandarin fish by scanning their complete genomic sequence. In total, two SNPs were found in PEP, one was found in TRY, and none were found in AMY. The D1(CTCC) and D5(TTTT) diplotypes in the PEP gene tended to show strong effects on the feeding habits of domesticated fish (p < 0.01). The results indicate that PEP may be associated with the genetic mechanism for feeding habits in mandarin fish, and the D1(CTCC) and D5(TTTT) diplotypes in the PEP gene may be useful markers for selecting mandarin fish with appropriate feeding habits for domestication.

Ontogeny of the stomach in yellow catfish (Pelteobagrus fulvidraco): detection and quantifictation of pepsinogen and H+/K+ -ATPase gene expression.

Yellow catfish (Pelteobagrus fulvidraco) is an important commercial species with high aquaculture potential in China. To better understand the process of digestive functioning of gastric gland development during the larval from 1 dph (day post-hatching) to 30 dph, real-time PCR was used to detect and quantify the pepsinogen and H(+) /K(+) -ATPase gene expression in P. fulvidraco. These data were also compared with the adult situation. The results showed that the expression of pepsinogen and H(+) /K(+) -ATPase genes in P. fulvidraco larvae both started at 1 dph, though the expression level was very low until 3 dph. The quantification of pepsinogen gene expression increased significantly from 4 to 8 dph, increased fluctuantly from 8 to 23 dph and rose sharply from 23 to 30 dph. In comparison with adult fish, there were no significant differences with larvae at 5 and 23 dph. However, data of 10 and 30 dph larvae were obviously higher than those of adult group. H(+) /K(+) -ATPase gene expression increased linearly from 1 to 30 dph. However, it was significantly lower than that of adult. The results show that P. fulvidraco larvae have an earlier functional stomach, though the function of the stomach is still not perfect. There is a gradual acidification environment within the stomach during the P. fulvidraco larvae development. Based on these results, we suggest that the weaning time for P. fulvidraco larvae would be much better after 23 dph.

[The clinical significance of GastroPanel in diagnostics of Helicobacter pylori eradication efficiency in patients with dyspepsia with correlation of family history of gastric cancer]. / Kliniczne znaczenie GastroPanelu w diagnostyce skutecznej eradykacji Helicobacter pylori u chorych z dyspepsja w zaleznosci od rodzinnego wystepowania raka zoladka.

UNLABELLED: Gastric cancer remains a significant medical and social problem. Familial, hereditary, social, and demographic factors increase the susceptibility of subjects to cancer development, especially those infected with Helicobacter pylori (H. pylori). Apart from genetic studies, there are ongoing biochemical studies of possible practical value in assessment of the risk of gastric cancer development. The GastroPanelBiohit test, that include determination of the levels of gastrin (G-17), pepsinogen I (PGI), pepsinogen II (PGII) and antibodies IgG/IgA against H. pylori in serum, allowed us to determine whether there are any abnormal changes in the gastric mucosa. The aim of the study was to determine whether GastroPanel parameters, identified in patients with dyspeptic symptoms (with or without history of gastric cancer in first degree relatives) before and after successful eradication of H. pylori, have any clinical value, especially in gastric cancer development. MATERIAL AND METHODS: The study comprised 61 patients aged 18-56 years with symptoms of dyspepsia. In all patients, the preliminary urea breath test (UBT) for the presence of H. pylori was performed and the positive result qualified for further study. For final analysis, 42 patients were approved, who were divided into two groups: group I (a control group) - 22 patients with negative family history of gastric cancer among the relatives of first degree, group II - 20 patients with positive history of gastric cancer among the relatives of first degree. All the patients had the gastroscopy with the biopsy of gastric mucosa for the histopathological evaluation. Additionally, the GastroPanel test was performed. RESULTS: In the blood serum of the patients with H. pylori infection, the concentrations of gastrin (G-17), pepsinogen I (PGI) and pepsinogen II (PGII) did not depend on family history of gastric cancer (p > 0.05). Successful eradication of H. pylori decreases the levels of G-17, PGI and PGII (statistical significance p < 0.05), and this correlates with the histopathological changes of gastric mucosa. The patients with positive family history of gastric cancer had more intense H. pylori colonization of gastric mucosa (IV degree of insensitivity of infection in UBT; group I - 22% vs group II - 69%) as compared to the control group. After effective eradication of H. pylori, statistically significant decreases of IgG H. pylori antibodies and of the level of gastrin (p < 0.05) in blood serum were seen (in a 3 months follow up) only in the control group. CONCLUSIONS: Independently of the history of familial gastric cancer, the GastroPanelBiohit test provides important clinical data useful for diagnosis, for assessment of effectiveness of H. pylori eradication therapy and in evaluation of the degree of the inflammatory changes in gastric mucosa.

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Pepsinogen/Proton Pump Co-Expression in Barrett's Esophageal Cells Induces Cancer-Associated Changes.

EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. OBJECTIVE: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H+ /K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+ /K+ ATPase proton pumps. STUDY DESIGN: In vitro translational. METHODS: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. RESULTS: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. CONCLUSIONS: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. LEVEL OF EVIDENCE: NA Laryngoscope, 133:59-69, 2023.

Analysis of gastrin-17 and its related influencing factors in physical examination results.

BACKGROUND: To analyze the difference of serum gastrin-17 (G17) level in healthy people with different sex, age, and body mass index (BMI), to explore the correlation between G17 and pepsinogen, and to study the influences of Helicobacter pylori (H. pylori) infection and various inflammatory factors on G17 secretion level. METHODS: A total of 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All subjects were tested for G17, pepsinogen I (PGI), pepsinogen II (PGII), PGI/PGII ratio (PGR), H. pylori, serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The difference of G17 secretion in different subjects and its correlation with PG were analyzed to investigate H. pylori infection and expound the effects of inflammatory indicators on G17. RESULTS: There was no significant difference in G17 secretion level in people with different sex, age and BMI (p > .05). G17 positively correlated with PGI and PGII, but negatively correlated with PGR. The G17 level of H. pylori-positive subjects was 10.16 ± 12.84, and prominently higher than that of H. pylori-negative subjects (3.27 ± 6.65). SAA and H. pylori infection were the greater risk factors for G17 abnormality among various indicators. CRP and ESR had no effect on G17 abnormality. CONCLUSIONS: G17 secretion is closely related to PG and H. pylori. Combined screening contributes to early screening of gastrointestinal diseases in normal people or groups at high risk for gastric cancer, but the influence of inflammatory indicators on G17 should be excluded to improve the reliability of the results.

[Restoration of secretory activity of digestive glands in conditions of acute hyperkinesis at persons with different levels of motor activity].

The dynamics' features of restoration reactions of the secretory function of gastric glands have been studied at patients with differences in the level and specificity of daily physical activity. The dependence between the level and characteristics of daily physical activity and reactivity of the secretory apparatus of the gastric glands in the recovery period after the muscle load has been established. The high reactivity of the secretory activity of digestive glands is typical for individuals with high level of daily physical activity. The differences of the functional stability of the secretion's mechanisms of various components of gastric juice under the influence of physical exercise and in recovery have been revealed. The greatest stability of the secretory mechanisms of digestive glands has been discovered at athletes practicing with the development of endurance--at skiers. Heterochronous reducing reactions of gastric and pancreatic secretion after physical stress have been defined. The reduction of secretion's mechanisms of gastric juice ingredients and the electrolyte and acid composition of digestive juices isn't simultaneous: the first order is for ferment's secretion. The inverse relationship between the content of digestive enzymes pepsinogen-1 and -2 in blood's serum and the concentration of proteolytic enzymes in the gastric content has been found at persons with various degrees of adaptation to the muscular tension.