Gastrin-related circRNA_0017065 promotes the proliferation and metastasis of colorectal cancer through the miR-3174/RBFOX2 axis.

Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.

Modern Management of Gastric Neuroendocrine Neoplasms.

OPINION STATEMENT: Gastric neuroendocrine neoplasms (G-NENs) are a heterogeneous group of tumors that broadly fall into two groups. The first group, driven by oversecretion of gastrin, are generally multifocal, small, and behave indolently with a low (but non-zero) risk of progression and metastatic spread. They are conventionally categorized into type 1, with endogenous gastric-based overproduction of gastrin, and type 2 G-NEN, with overproduction of gastrin from an extra-gastric gastrin-secreting tumor. The second group, termed type 3 G-NEN, occur spontaneously and are potentially more aggressive, having a clinical course analogous to other neuroendocrine tumors of the gastrointestinal tract. Type 1 G-NEN can be managed with endoscopic surveillance and resection of visible lesions with great success, reserving surgery for the rare high-risk lesion, whereas surgical resection of the causative gastrin-secreting tumor in type 2 G-NEN is usually curative. Type 3 G-NEN is usually managed with formal surgical resection but there is growing evidence that limited surgery or even endoscopic resection in appropriately selected patients with low risk is both safe and effective. A novel subtype of G-NEN, associated with long-term proton pump inhibitor usage, is increasing in incidence. The pathophysiology seems to parallel type 1 G-NEN. In the setting of metastatic disease, which can occur in any subtype but is most common by far in type 3 G-NEN, the lack of trial data unique to G-NEN results in extrapolation of strategies and agents for treatment of non-gastric neuroendocrine disease. The rapid pace of development in this area is likely to benefit the metastatic G-NEN patient as well. As treatment is predicate on type of G-NEN, establishing the etiology of the lesion is crucial but growing knowledge of G-NEN pathophysiology and close collaboration between pathologists, gastroenterologists, radiologists, surgeons, and oncologists have enabled a growing trend towards de-escalation and less-invasive treatment paradigms.

A pathway for detection of gastric cancer biomarkers via using a layer-by-layer coated D-shaped grinding long-period fiber grating sensor.

Gastric cancer significantly contributes to global cancer mortality, often leading to inoperable stages and high recurrence rates post-surgery. Elevated levels of G-17 and G-gly have been identified as potential risk factors, particularly in patients with duodenal ulcers. This study introduces an innovative D-shaped grinding long-period fiber grating sensor (D-LLPFGs) designed for non-invasive detection of the gastrin G-17 antigen, employing a layer-by-layer chemical self-assembly to bond G-17 antibodies onto the fiber surface through hydrogen bonding. The D-LLPFGs sensor demonstrated significant spectral shifts within 1 min of antigen-antibody interaction, highlighting its rapid detection capability. At an optimized antibody concentration of 4 µg/ml, antigen testing across different concentrations (10, 12.5, 20, 50 µg/ml) showed peak changes at 12.5 µg/ml antigen, with a 1.186 nm shift and 0.503 dB loss. The sensor exhibited a wavelength sensitivity of 0.095 nm/µg/ml, indicating its high sensitivity and potential in gastric cancer classification, diagnosis, and treatment. This research concludes that the D-shaped fiber sensor is an effective and sensitive tool for detecting G-17 antigen levels, presenting a significant advancement in non-invasive gastric cancer diagnosis. Its quick response time and high sensitivity highlight its potential for broad biomedical applications, offering a new avenue for early cancer detection and improving patient prognosis. The success of this study opens the door to further exploration and implementation of fiber optic sensors in clinical settings, marking a significant step forward in the fight against gastric cancer.

Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes.

Introduction: PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Methods: Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 µl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. Result: The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in ß-cell numbers between groups. Conclusion: Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.

Diagnostic value of combined detection of three gastric functions and Helicobacter pylori typing in chronic gastritis and gastric cancer.

This research attempted to clarify the clinical diagnostic value of combined detection of gastric function and Helicobacter pylori (Hp) serotyping in chronic gastritis and gastric cancer (GC). The 80 chronic non atrophic gastritis (CNAG) patients treated in our hospital from October 2021 to October 2022 received selection as the CNAG group. The 96 chronic atrophic gastritis (CAG) patients diagnosed by gastroscopy and pathology in the same period received selection as CAG group. During the same period, 50 patients diagnosed with GC received inclusion in GC group. Pepsin I (PG I), PG II (PG II), gastrin-17 (G-17) and Hp serotyping received detection and comparison in three groups. The diagnostic efficacy of PG Ⅰ, PG Ⅱ, G-17, the ratio of serum PG I to PG II (PGR), and Hp serotyping in chronic gastritis and GC received evaluation by receiver operating characteristic (ROC). Relative to in the CNAG group, PG I and PGR levels in the other two groups exhibited depletion (P < 0.05); no statistical significance was observed in the PG II level among the three groups (P > 0.05); relative to the CNAG group, the G-17 level in the other two groups exhibited elevation (P < 0.05). Total Hp positive rate was 61.06 %, among which GC group exhibited the highest positive rate (72.00 %), and type I Hp positive rate also exhibited the highest in GC group (60.00 %). The type II Hp positive rate exhibited the highest in CNAG group (15.00 %). The PG I and PGR levels in type I Hp positive patients exhibited depletion relative to those in type II Hp positive patients, whereas PG II and G-17 levels exhibited elevation. When testing each indicator alone, the area under the curve (AUC) of PG I exhibited the highest in CNAG group, which was 0.874. When testing each indicator alone, AUC of Hp typing exhibited the highest in CAG group, which was 0.515. When testing each indicator alone, AUC of G-17 exhibited the highest in GC group, which was 0.787. The performance of combined detection was better than that of individual detection, with AUCs greater than 0.9 in three groups. In conclusion, changes in PG I, PG II, PGR and G-17 levels and Hp serotyping can receive application as screening indicators for chronic gastritis and GC, which can reflect relevant status of gastric mucosa to varying degrees. Combined detection of indicators has higher diagnostic performance and can receive application as an auxiliary diagnostic indicator in addition to gastroscopy biopsy, providing a reference basis for the formulation of clinical diagnosis and treatment plans.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study.

BACKGROUND AND OBJECTIVE: A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. METHODS: Male and female subjects (n = 135; age: 25-60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. RESULTS: CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants' vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. CONCLUSION: The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Among bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide. METHODS: In 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured. RESULTS: SG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group. CONCLUSION: Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Distribution of cionin, a cholecystokinin/gastrin family peptide, and its receptor in the central nervous system of Ciona intestinalis type A.

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.

Effects of Desmodium caudatum on Gastrointestinal Hormones and Intestinal Flora in Rats with Gastritis.

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.

Reference Interval of Serum Gastrin 17 (G-17) for Healthy Population: A Non-Invasive Screening Biomarker for Gastric Disorders.

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.

The role of gastrin 17 and pepsinogen I:pepsinogen II ratio in pathological diagnosis and endoscopic selection in gastritis patients.

BACKGROUND: The noninvasive serum markers pepsinogen I (PGI), pepsinogen II (PGII), gastrin-17 (G17), and PGI:PGII ratio (PGR) have recently been proposed as a new tool for predicting various gastric pathologies. METHODS: A total of 83 gastritis patients confirmed by gastroscopy were enrolled, with 78 undergoing concurrent colonoscopies. The control group included 99 healthy subjects. Enzyme-linked immunosorbent assay was used to detect PGI, PGII, G17, and PGR. The performance of serological analysis for detecting gastritis pathology was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The G17 and PGII levels increased significantly (P < .001), whereas PGR levels decreased (P = .001) in the gastritis group. The ROC analysis revealed that PGR had a sensitivity and specificity of 70.83% and 86.67%, respectively, in predicting Helicobacter pylori-infected gastritis and a sensitivity and specificity of 88% and 65.52%, respectively, in predicting active gastritis. The G17 levels were significantly elevated in gastritis patients undergoing concurrent colonoscopies (P < .05). CONCLUSION: Pepsinogen I:pepsinogen II ratio was found to be a useful predictor of active gastritis and H pylori-infected gastritis. Furthermore, G17 was found to be closely related to pathological conditions found by colonoscopy and may provide recommendations for whether gastritis patients should undergo a concurrent colonoscopy.

Neglected function of gastrin to reduce feeding in Siberian sturgeon (Acipenser baerii) via cholecystokinin receptor B.

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.

Marginal Ulcer Incidence and the Population of Gastrin Producing G cells Retained in the Gastric Pouch after Roux-en-Y Gastric Bypass: Is There a Relationship?

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.

The cckOMA syndrome and its relation to the Zollinger-Ellison syndrome: a diagnostic challenge.

OBJECTIVE: Among patients with enteropancreatic neuroendocrine tumor syndromes only one case with a cholecystokinin (CCK) secreting tumor has been reported. She had significant hyperCCKemia leading to a specific syndrome of severe diarrheas, weight loss, repeated duodenal ulcers and a permanently contracted gallbladder with gallstones. There are, however, reasons to believe that further CCKomas exist, for instance among Zollinger-Ellison patients with normal plasma gastrin concentrations. The present review is a call to gastroenterologists for awareness of such CCKoma patients. METHOD: After a short case report, the normal endocrine and oncological biology of CCK is described. Subsequently, the CCKoma symptoms are discussed with particular reference to the partly overlapping symptoms of the Zollinger-Ellison syndrome. In this context, the diagnostic use of truly specific CCK and gastrin assays are emphasized. The discussion also entails the problem of access to accurate CCK measurements. CONCLUSION: Obviously, the clinical awareness about the CCKoma syndrome is limited. Moreover, it is also likely that the knowledge about the necessary specificity demands of diagnostic gastrin and CCK assays have obscured proper diagnosis of the CCKoma syndromes in man.

Personalized treatment of well-differentiated gastric neuroendocrine tumors based on clinicopathological classification and grading: A multicenter retrospective study.

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.