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Background: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension.Methods: Adult intestine-specific Cckbr-knockout mice (Cckbrfl/flvillin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6-7 weeks) on intestinal Na+/H+ exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbrfl/flvillin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbrfl/flvillin mice and SS13BN rats. We constructed gastrin-SiO2 microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation.Results: Gastrin-SiO2 microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na+/H+ exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na+/H+ exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2.Conclusions: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO2 microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: It has been proposed that the combination of gastrin-17 (G-17), pepsinogens I and II (PGI and PGII), and anti-Helicobacter pylori (H. pylori) antibodies (GastroPanel®, BIOHIT HealthCare, Helsinki, Finland) could serve as biomarkers of atrophic gastritis. OBJECTIVE: This study aimed to ensure the diagnostic accuracy of GastroPanel® and evaluate the effect of proton pump inhibitors (PPIs) on these biomarkers. METHODS: Dyspeptic patients who underwent gastrointestinal endoscopy were enrolled in the present study. Histological findings, which were the gold standard to stratify groups, were as follows: no atrophy (controls); antrum atrophy; corpus atrophy; multifocal atrophy; and neoplasia. G-17, PGI, PGII, and anti-H. pylori immunoglobulin (Ig)G antibodies were assayed using commercially available kits. The ratio of PGI/PGII was calculated. RESULTS: Among 308 patients, 159 (51.6%) were PPI users. The overall prevalence of atrophy was 43.8% (n=135). Ninety-two (29.9%) patients were H. pylori positive according to anti-H. pylori IgG levels. G-17 levels were not low in those with antrum atrophy but were high in those with corpus and multifocal atrophies. PGI levels were significantly lower in those with corpus and multifocal atrophies. The sensitivity of PGI

Ethnopharmacological Relevance: Baizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored., Aim of the Study: This study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD)., Methods: To simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin β (β-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated., Results: The results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (β-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wang Chenxing: Investigation, Data curation, Writing – original draft, preparation. Su Jie: Data curation, Writing – original draft. Tian Yajuan: Investigation, Data curation. Li Ting: Conceptualization, Methodology. Zhong Yuying: Investigation. Chen Suhong: Writing – review & editing. Lv Guiyuan: Methodology, Validation, Writing – review & editing., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Copyright of Chinese Journal of Clinical Healthcare is the property of Chinese Journal of Clinical Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Marginal ulcers are the most prevalent endoscopic abnormality after RYGB. The etiology is still poorly understood; however, an increase in acid secretion has been strongly implicated as a causal agent. Although gastrin is the greatest stimulant of acid secretion, to date, the presence of gastrin producing G cells retained in the gastric pouch, related to the occurrence of marginal ulcers, has not been evaluated., Objective: Evaluate the density of G cells and parietal cells in the gastric pouch of RYGB patients with a diagnosis of marginal ulcer on the post-op EGD., Method: We retrospectively evaluated 1104 gastric bypasses performed between 2010 and 2020. Patients with marginal ulcer who met the inclusion criteria and controls were selected from this same population. Endoscopic gastric pouch biopsies were evaluated using immunohistochemical study and HE staining to assess G cell and parietal cell density., Results: In total, 572 (51.8%) of the patients performed endoscopic follow-up after RYGB. The incidence of marginal ulcer was 23/572 (4%), and 3 patients required revision surgery due to a recalcitrant ulcer. The mean time for ulcer identification was 24.3 months (2-62). G cell count per high-power field (× 400) was statistically higher in the ulcer group (p < 0.05). There was no statistical difference in parietal cell density between groups (p 0.251)., Conclusion: Patients with a marginal ulcer after gastric bypass present a higher density of gastrin-producing G cells retained in the gastric pouch., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The incidence of well-differentiated gastric neuroendocrine tumors (G-NET) is increasing annually, and while they have a good prognosis and low mortality rate, their high recurrence rate makes treatment options controversial. This study aims to determine the relationship between individualized treatment plans and the recurrence of G-NET., Methods: We performed a multicenter, retrospective study of 94 patients with highly differentiated G-NET and treated at Peking Union Medical College Hospital, Yantai Yuhuangding Hospital, and Beijing Zhong-Neng-Jian Hospital from November 2015 to September 2023. Risk factors for recurrence of G-NETs were investigated using chi-squared test and multifactorial logistic regression analysis., Results: After a median follow-up of 49 months, the overall recurrence rate among the 94 G-NET patients was 14% (13/94). The recurrence rates of endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), somatostatin analog (SSA) therapy, and surgery were 43% (6/14), 10% (5/49), 5% (1/22), and 11% (1/9), respectively. Post-treatment recurrence rates were significantly different ( P = 0.014) among four treatments (EMR, ESD, SSA, and surgery), and further subgroup comparisons revealed lower recurrence rates in the ESD and SSA groups than in the EMR group. From the second month onward, SSA therapy considerably reduced the gastrin levels from 1081.0 (571.5, 2472.8) pg/mL to 461.5 (255.3, 795.0) pg/mL ( Z = -3.521, P <0.001). Both chi-squared test and multifactorial logistic regression analysis suggested that among the clinicopathological parameters studied, only the pre-treatment gastrin level ( P = 0.018 and 0.005) and the type of treatment ( P = 0.014 and 0.017) were significantly associated with G-NET recurrence., Conclusions: Individualized treatment strategies may reduce the risk of relapse after G-NET treatment. Long-term SSA therapy may be a secure and efficacious treatment option for type 1 G-NET with more than six lesions, and it substantially decreases the incidence of post-treatment recurrence., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

The cholecystokinin (CCK)/gastrin family peptides are involved in regulation of feeding and digestion in vertebrates. In the ascidian Ciona intestinalis type A (Ciona robusta), cionin, a CCK/gastrin family peptide, has been identified. Cionin is expressed exclusively in the central nervous system (CNS). In contrast, cionin receptor expression has been detected in the CNS, digestive tract, and ovary. Although cionin has been reported to be involved in ovulation, its physiological function in the CNS remains to be investigated. To elucidate its neural function, in the present study, we analyzed the expression of cionin and cionin receptors in the CNS. Cionin was expressed mainly in neurons residing in the anterior region of the cerebral ganglion. In contrast, the gene expressin of the cionin receptor gene CioR1, was detected in the middle part of the cerebral ganglion and showed a similar expression pattern to that of VACHT, a cholinergic neuron marker gene. Moreover, CioR1 was found to be expressed in cholinergic neurons. Consequently, these results suggest that cionin interacts with cholinergic neurons as a neurotransmitter or neuromodulator via CioR1. This study provides insights into a biological role of a CCK/gastrin family peptide in the CNS of ascidians., (© 2024. The Author(s).)

In order to preliminarily explore the effects of Desmodium caudatum on gastritis and intestinal flora in rats, a chronic gastritis rat model was established using the classic sodium salicylate method. Eighteen SPF rats were divided into three groups: the control group (Group C), the model group (Group M), and the treatment group (Group T). Pathological sections of the gastric wall were taken from rats in each group. Furthermore, the concentrations of gastrin and malondialdehyde in the serum of rats in each group were determined by ELISA. Additionally, the effects of D. caudatum on the intestinal flora of rats with gastritis were explored through a detailed comparison of gut bacterial communities in the three groups, employing Illumina-based 16S rRNA gene sequencing. The results indicated that D. caudatum decoction could reduce the malondialdehyde content and increase the gastrin content. Moreover, D. caudatum decoction was found to enhance the diversity and abundance of intestinal flora, exerting a positive impact on the treatment of gastritis by regulating and restoring the intestinal flora.

Objective: To analyse fasting serum concentrations of G-17 in healthy individuals to establish the reference intervals (RIs) in the Pakistani population., Study Design: Cross-sectional, observational study. Place and Duration of the Study: Department of Clinical Chemistry and Immunology, Chughtai Institute of Pathology, Lahore, Pakistan, from October to December 2022., Methodology: Fasting serum samples from one hundred and twenty healthy individuals between the age of 18-65 years were collected according to the CLSI recommendations after taking written informed consent. Samples were analysed on the auto-analyser for the quantitative measurement of serum G-17 by sandwich chemiluminescence immunoassay. Kolmogorov-Smirnov test was applied to check normality. A p-value of <0.05 was considered significant; 2.5th and 97.5th percentiles were computed using the formula 0.025 (n+1) and 0.0975 (n+1), respectively., Results: Of the 120 samples, 74 were obtained from male patients and 46 from females. The mean age was 30.2 ±10.36 years. The histogram revealed a non-parametric distribution of the data. The established reference intervals by the rank-based method were 2.31 pg/mL and 49.36 pg/mL which corresponds to 2.5th and 97.5th percentiles, respectively. These were markedly different from the Chinese reference ranges., Conclusion: Ethnic and geographic variations affect the trends of RIs of Serum G-17. There is a need to establish its population-specific RIs for G-17, so it can be used as a non-invasive option in identifying patients requiring invasive endoscopic intervention., Key Words: Gastrin, Atrophic Gastritis, Biomarker, Reference values.

Ethnopharmacological Relevance: Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear., Aim of the Study: To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms., Materials and Methods: Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1β, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD., Results: The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1β, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5., Conclusion: Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors., (© 2023. Society of Surgical Oncology.)

Background: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis., Methods: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests., Results: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17 hi PGI low ). Univariate logistic regression showed that G17 hi PGI low was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17 hi PGI low group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17 hi PGI low group., Conclusion: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17 hi PGI low , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17 hi PGI low and non-G17 hi PGI low groups may represent different etiologies of B12 deficiency., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels., Methods: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females)., Results: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785)., Conclusions: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion.

Objective To investigate the diagnostic value of MG7-Ag single detection and the combination detection of PG, G-17 and helicobacter pylori(Hp)infection in gastric cancer. Methods The literatures about MG7-Ag single detection and the combination detetion of PG, G-17 and Hp infection in diagnosing gastric cancer were retrieved from the databases of PubMed, CNKI, Wan Fang and VIP databases, and the retrieval time was from the database establishment to September 2019. Two researchers independently screened the literatures, extracted the data according to inclusion and exclusion criteria, and used the QUADAS 2 tool in the Review Manager 5.3 software to conduct the quality evaluation on the obtained literatures. The gastroscopy and mucous membrane biopsy served as the golden standard. Specificity (SEN), specificity(SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the ROC curve (AUC) and relative diagnostic odds ratio of the above two methods were pooled respectively by adopting the Stata/SE 15.1 software. Results A total of 2 072 articles were retrieved and 22 articles were finally included, involving 7 166 patients.The pooled SEN, SPE, PLR, NLR, DOR and AUC of MG7-Ag single detection in diagnosing gastric cancer were 0.67 (95%CI:0.58-0.75), 0.91 (95%CI:0.89-0.93), 7.75 (95%CI:5.76-10.43), 0.36 (95%CI:0.28-0.47), 21.47 (95%CI:13.43-34.31) and 0.91 (95%CI:0.88-0.93)respectively;which of combination detection of PG, G-17 and Hp infection were 0.78 (95%CI:0.53-0.92), 0.92(95%CI:0.88-0.95), 10.20 (95%CI:6.78-15.37), 0.24 (95%CI:0.10-0.58), 43.10 (95%CI:16.54-112.32) and 0.94 (95%CI:0.92-0.96) respectively.Compared with MG7-Ag single detection, the relative diagnostic odds ratio of combination detection of PG, G-17 and Hp infection was 1.91 (95%CI:0.65-5.62). Conclusion The sensitivity of combination detection of PG, G-17 and Hp infection in diagnosing gastric cancer is better than the MG7-Ag single detection, and the other indicators have no obvious difference in the aspect of diagnostic value. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT)., Hypothesis/objectives: (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT., Animals: Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT., Methods: Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty-four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs., Results: Twenty-seven of 151 PHPT dogs (17.9%) had increased pre-treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P < .001) and iCa concentrations (P < .001), but not gastrin concentrations (P = .15). The proportion of dogs with hypergastrinemia with and without GI signs did not differ (P = 1.00)., Conclusions and Clinical Importance: Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35-86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively. We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs., Objective: The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration., Methods: Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables., Results: The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84)., Conclusions: A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof., (© 2023 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Notch signaling regulates gastrointestinal stem cell proliferation and differentiation yet Notch-regulated transcriptional effectors of gastric epithelial cell differentiation are poorly understood. Here we tested the role of the bHLH transcription factor Achaete-Scute homolog 1 (ASCL1) in gastric epithelial cell differentiation, and its regulation by Notch. Newborn Ascl1 null mice showed a loss of expression of markers of neurogenin-3-dependent enteroendocrine cells, with normal expression of enterochromaffin-like cells, mucous cells, chief cells, and parietal cells. In adult mice, Ascl1 gene expression was observed in the stomach, but not the intestine, with higher expression in antral than corpus epithelium. Lineage tracing in Ascl1-CreER T2 ; Rosa26-LSL-tdTomato mice revealed single, scattered ASCL1 + cells in the gastric epithelium, demonstrating expression in antral gastrin- and serotonin-producing endocrine cells. ASCL1-expressing endocrine cells persisted for several weeks posttamoxifen labeling with a half-life of approximately 2 months. Lineage tracing in Gastrin-CreER T2 mice demonstrated a similar lifespan for gastrin-producing cells, confirming that gastric endocrine cells are long-lived. Finally, treatment of Ascl1-CreER T2 ; Rosa26-LSL-tdTomato mice with the pan-Notch inhibitor dibenzazepine increased the number of lineage-labeled cells in the gastric antrum, suggesting that Notch signaling normally inhibits Ascl1 expression. Notch regulation of Ascl1 was also demonstrated in a genetic mouse model of Notch activation, as well as Notch-manipulated antral organoid cultures, thus suggesting that ASCL1 is a key downstream Notch pathway effector promoting endocrine cell differentiation in the gastric epithelium. NEW & NOTEWORTHY Although Notch signaling is known to regulate cellular differentiation in the stomach, downstream effectors are poorly described. Here we demonstrate that the bHLH transcription factor ASCL1 is expressed in endocrine cells in the stomach and is required for formation of neurogenin-3-dependent enteroendocrine cells but not enterochromaffin-like cells. We also demonstrate that Ascl1 expression is inhibited by Notch signaling, suggesting that ASCL1 is a Notch-regulated transcriptional effector directing enteroendocrine cell fate in the mouse stomach.

The physiology of gastric acid secretion is one of the earliest subjects in medical literature and has been continuously studied since 1833. Starting with the notion that neural stimulation alone drives acid secretion, progress in understanding the physiology and pathophysiology of this process has led to the development of therapeutic strategies for patients with acid-related diseases. For instance, understanding the physiology of parietal cells led to the developments of histamine 2 receptor blockers, proton pump inhibitors (PPIs), and recently, potassium-competitive acid blockers. Furthermore, understanding the physiology and pathophysiology of gastrin has led to the development of gastrin/CCK 2 receptor (CCK 2 R) antagonists. The need for refinement of existing drugs in patients have led to second and third generation drugs with better efficacy at blocking acid secretion. Further understanding of the mechanism of acid secretion by gene targeting in mice has enabled us to dissect the unique role for each regulator to leverage and justify the development of new targeted therapeutics for acid-related disorders. Further research on the mechanism of stimulation of gastric acid secretion and the physiological significances of gastric acidity in gut microbiome is needed in the future., (© 2023 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD., Hypothesis: To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups., Animals: Thirteen dogs with CKD; 10 aged-matched healthy dogs., Methods: Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA., Results: No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05)., Conclusions and Clinical Importance: Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important., Content: The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods., Summary: Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG)., Methods: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]., Results: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways., Conclusions: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.

Background: Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG))., Aim: To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA)., Methods: Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG., Results: Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis., Conclusions: Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis., Competing Interests: Conflict of Interest The authors listed above declare no conflict of interest for this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion., Methods: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation., Results: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups., Conclusion: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Forough Saki et al.)

Background: Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa., Aims: We investigate the incidence of gastric polyps in CAAG patients., Methods: This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded., Results: A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively)., Conclusion: CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG., Competing Interests: Declaration of Competing Interest The Authors have no conflicts of interest to declare., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of the study was to determine the proportion of gastric cancer patients with decreased levels of pepsinogen and gastrin-17 in plasma, with the goal of providing indirect evidence of the sensitivity of these biomarkers when applied in a cancer screening setting., Methods: The levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori immunoglobulin antibodies in plasma samples of gastric cancer patients were evaluated using the GastroPanel test system (Biohit Oyj, Helsinki, Finland). A decreased level of the pepsinogen I/II ratio was defined as less than three, while a decrease in gastrin-17 was defined as less than 1 pmol/L. Univariate analysis using non-parametric tests was used to investigate differences between normal and low concentrations of biomarkers., Results: In total, 481 plasma samples from patients (59.9% male) with a median age of 64 years (ranging from 27 to 88 years) were analyzed. Out of the 400 cases of gastric cancer (83.2% of the total), 182 were categorized as the intestinal type, 141 as the diffuse type, 60 as the mixed type, and 17 as indeterminate according to the Lauren classification system. The H. pylori immunoglobulin test was positive in 74.0% of the patients. Pepsinogen I/II ratio was decreased in 32.4% (36.8% of the intestinal type); gastrin-17 in 12.3% (10.1% of the antral region) of all cases., Conclusion: The majority of gastric cancer patients had normal levels of pepsinogen and gastrin-17, suggesting that these biomarkers have limited application as screening tools in the Caucasian population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The pathogenesis for non-type 1/2 gastric neuroendocrine tumors (G-NETs) remains unclear. The aim of this study was to examine the clinicopathologic features of G-NETs and associated mucosal changes., Methods: The electronic health records of patients with non-type 1/2 G-NETs were reviewed. H&E slides were reviewed for pathologic features and mucosal changes. The t test and Fisher exact test were used for statistical analysis., Results: In total, 33 patients were assigned to either group 1 (n = 23) or group 2 (n = 10). Group 1 included patients with a history of proton pump inhibitor (PPI) use, increased gastrin levels, or significant PPI effect (PPI/gastrin-associated). All other patients were assigned to group 2. There was no significant difference in age and sex between the 2 groups. Group 2 tumors were more likely to be larger, invade deeper, and develop metastases (P < .05). Tumors in patients with cirrhosis tended to be larger. Peritumoral mucosal changes included loss of oxyntic glands, foveolar hyperplasia, and intestinal metaplasia. Background mucosa in group 1 patients showed PPI effect and neuroendocrine hyperplasia or dysplasia., Conclusions: Although PPI/gastrin-associated non-type 1/2 G-NETs were smaller and more indolent than typical type 3 G-NETs, tumors in patients with cirrhosis tended to be larger. Additionally, peritumoral mucosal changes could mimic chronic atrophic gastritis., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)