Search

ABSTRACT Metal–organic framework (MOF) is a porous material composed of metal ions/clusters and organic ligands. It has attracted much attention due to its high specific surface area, good biocompatibility, chemical modifiability, and diversity of components. Among many MOFs, zirconium‐based MOFs are particularly suitable for biological applications due to their optimal stability and low toxicity to hydrolysis. However, due to the weak coordination bonds between many metal clusters and organic ligands, most MOFs are prone to collapse in acidic environments, and the stability of MOFs as drug carriers cannot be guaranteed so that they cannot be widely used as oral drug carriers. This study synthesized the three MOFs using metal Zr ion clusters as the center and different nitrogen‐containing organic ligands, which are stable in gastric acid, namely, UiO‐66‐PDC, UiO‐66‐NH2, and UiO‐66‐NO2. The anionic drug loxoprofen (LOX) was loaded and characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and x‐ray diffraction. The adsorption and release behaviors of LOX and the three MOFs were studied from the molecular point of view by computer simulation. A series of behaviors and mechanisms of pH‐responsive nitrogen‐containing MOFs as oral drug carriers were further explored through rat pharmacokinetic experiments, the everted gut sac experiments, and intestinal absorption mechanism experiments. The experimental results show that there is a strong electrostatic interaction between anionic drug LOX and UiO‐66‐PDC under simulated gastric acid environment, which prolongs the half‐life of the drug, proving that LOX@UiO‐66‐PDC is a promising new oral drug delivery system. [ABSTRACT FROM AUTHOR]

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2–receptor antagonists (H2RAs). Emerging evidence also supports potassium‐competitive acid blockers (P‐CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H2RAs, PPIs and P‐CABs. By literature search, we identified studies of H2RAs, PPIs or P‐CABs that reported mean pH >4 HTRs at steady state (days 5–8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non‐linear, mixed‐effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P‐CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P‐CABs, 17.3% for PPIs and 0% for H2RAs. P‐CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis. [ABSTRACT FROM AUTHOR]

Summary Porang tubers (Amorphophallus oncophyllus) are one of the Araceae family plants, which naturally contain resistant starch (RS). The RS is able to provide health impacts such as reducing the glycaemic index (GI), preventing the formation of gallstones and cardiovascular disease, and increasing mineral absorption. This research aims to improve the RS and prebiotic properties of porang flour through physical, chemical, enzymatic and microbiological modifications. Research methods include modification with physical treatment of autoclaving‐cooling one and two cycles (AC‐1S and AC‐2S), microwave‐cooling (MWC), heat moisture treatment (HMT), annealing (ANN), chemical treatment with acid hydrolysis (HA), enzymatic treatment with pullulanase debranching (DP) and microbiological treatment with combined heating and cooling fermentation (FAC). The results showed that physical, chemical, enzymatic and fermentation modification techniques increased the characteristics of RS and the prebiotic properties of porang flour. The best modification method for porang flour was obtained in the DP treatment with the morphological characteristics of sharp‐surfaced granules, total starch 39.81%, amylose content 3.73%, amylopectin content 36.08%, reducing sugar content 16.31%, power digestibility 43.81%, very rapidly digestible starch (VRDS) 8.59%, rapidly digestible starch (RDS) 11.08%, slowly digestible starch (SDS) 23.60%, RS 56.73%, resistance to gastric acid 98.60%, lactic acid bacteria (LAB) viability 11.87 log cfu/ml, prebiotic effect 3.07, prebiotic index 2.46 and prebiotic activity 1.77. [ABSTRACT FROM AUTHOR]

Summary: The human gastrointestinal tract hosts a diverse and intricate microbial community, a pivotal contributor to human well‐being. An effective strategy for exploring the diversity and potential probiotic attributes of Bacillus species is to isolate them from faecal samples. In this investigation, we scrutinised the in vitro probiotic characteristics of Bacillus coagulans VHBAX‐04, an isolate derived from human faeces. These attributes encompassed acid and gastric juice tolerance, resistance to bile salts and intestinal juice, adhesion capabilities, safety profile, antibiotic resistance pattern, the absence of toxin genes, and antimicrobial efficacy. Furthermore, we conducted in silico analyses to evaluate its probiotic potential. The notable absence of genes associated with mucin degradation, red blood cell lysis, gelatin hydrolysis, or toxin production in B. coagulans VHBAX‐04 certifies its safety as a probiotic. Additionally, the distinct antibiotic resistance pattern of strain VHBAX‐04 suggests its potential for co‐administration with antibiotics. In conclusion, this study underscores the suitability of B. coagulans VHBAX‐04 as a viable probiotic option. Isolation and Evaluation of Bacillus coagulans WBX04: A Probiotic Strain from Human Feces Studied through 16S rRNA Sequencing and In Vitro Tests. [ABSTRACT FROM AUTHOR]

Introduction: Postpartum depression is one of the most common non‐obstetric postnatal complications. As the microbiome (and gut–brain axis) as well as inflammation may be involved in the mechanism, we aimed to assess if antibiotic or gastric acid inhibition use during pregnancy affects the risk of postpartum depression (clinical diagnosis and/or antidepressant use up to 1 year after childbirth). Material and Methods: This population‐based cohort study used first singleton pregnancy resulting in a live birth in Sweden from 2006 to 2016. Women with history of depression were excluded. Multivariable logistic regression models were used to assess the impact of antibiotics and gastric acid inhibitors and other risk factors, presented as odds ratios (ORs) with 95% confidence intervals (CI). Results: Overall, 29% of all 10 666 women with postpartum depression were exposed to antibiotics and 6.2% to gastric acid inhibitors, compared to, respectively, 21% and 3.2% of 613 205 women without postpartum depression. Antibiotic use during pregnancy was associated with postpartum depression (OR 1.43, 95% CI 1.37–1.49), particularly for quinolones and other antibacterials (including nitroimidazole derivatives). Gastric acid inhibition was associated with an even higher risk than antibiotics (OR 2.04, 95% CI 1.88–2.21). Both antibiotics and gastric acid inhibitors suggested higher risk with increased dose in a dose–response analysis. Conclusions: The use of antibiotics and gastric acid inhibition drugs during pregnancy appeared to be associated with a higher risk of postpartum depression. However, it is important to consider that other predisposing factors could contribute to this increased risk, even after excluding individuals with a history of depression. [ABSTRACT FROM AUTHOR]

We conducted this three‐part study in healthy subjects to investigate the pharmacokinetics of tasurgratinib (orally available selective inhibitor of fibroblast growth factor receptor 1–3) and M2 (its major metabolite) under different conditions. In Part A, subjects received tasurgratinib 35 mg either fed with a high‐fat meal or fasted. In Parts B and C, subjects received tasurgratinib 35 mg alone or with either rabeprazole (acid‐reducing agent) 20 mg (Part B) or rifampin (strong CYP3A inducer) 600 mg (Part C). Primary endpoints were maximum concentration (Cmax), and areas under the plasma concentration–time curve to time of last quantifiable concentration (AUC(0–t)) and extrapolated to infinite time (AUC(0–inf)). Forty‐two subjects were enrolled, 14 each into Parts A, B, and C. In Part A, administration of tasurgratinib with a high‐fat meal resulted in 33% reduction in Cmax and ∼23% reduction in AUC(0–t) and AUC(0–inf) of tasurgratinib, and 47% reduction in Cmax with ∼30% reduction in AUC(0–t) and AUC(0–inf) of M2. In Part B, co‐administration of rabeprazole at steady state resulted in no/weak interaction with tasurgratinib (∼8% increase in AUC(0–t) and AUC(0–inf) without an effect on Cmax) and M2 (∼18% increase in AUC(0–t) and AUC(0–inf) without an effect on Cmax). In Part C, co‐administration of rifampin at steady state resulted in a weak interaction with tasurgratinib (∼16% reduction in AUC(0–t) and AUC(0–inf)) and M2 (∼12% reduction in AUC(0‐t) and AUC(0‐inf)). Administration of tasurgratinib with a high‐fat meal appeared to reduce systemic exposure of tasurgratinib, however co‐administration with an acid‐reducing agent or a CYP3A inducer had a minimal impact on pharmacokinetics. [ABSTRACT FROM AUTHOR]

This study investigates the dynamic fluctuations of pH caused by gastric acid secretion, a process of both biological and clinical significance, with microrobots. Abnormal patterns of acidity often indicate gastrointestinal diseases, underlying the importance of precise intragastric pH monitoring. Traditional methods using fluorescent probes face challenges due to their faint solid‐state fluorescence, limited target specificity, and accuracy. To overcome these obstacles, pH‐responsive fluorescent organic microparticles decorated with magnetite (Fe3O4) nanoparticles are engineered. These microrobots exhibit a unique fluorescence switching capability at a critical pH, enabling the monitoring of gastric acidity. The magnetic part of these microrobots ensures magnetic maneuverability to enable targeted navigation. The microrobots' fluorescence switching mechanism is elucidated through comprehensive spectroscopy, microscopy, and X‐ray diffraction analyses, revealing molecular‐level structural transformations upon interaction with gastric acid and antacids. These transformations, specifically protonation and deprotonation of the microrobots' fluorescent components, prompt a distinct fluorescence response correlating with pH shifts. In vitro and ex vivo experiments, simulating stomach conditions, confirm the microrobots' efficacy in pH‐responsive imaging. The results showcase the promising diagnostic potential of microrobots for gastrointestinal tract diseases, marking a significant advancement in imaging‐based medical diagnostics at targeted locations. [ABSTRACT FROM AUTHOR]

Background: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. Hypothesis: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. Animals: Fifty‐one dogs with mast cell tumors (MCTs). Materials and Methods: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine‐2‐receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre‐ and post‐treatment time points, and between pre‐ and post‐time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. Results: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre‐ to post‐treatment (3.429; range, 1.417–15 to 5.631; range, 2.654–92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. Conclusions: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a complex neuropsychiatric disorder widely recognized for its impaired bioenergy utilization. The astrocyte‐neuron lactate shuttle (ANLS) plays a critical role in brain energy supply. Recent studies have revealed abnormal lactate metabolism in SCZ, which is associated with mitochondrial dysfunction, tissue hypoxia, gastric acid retention, oxidative stress, neuroinflammation, abnormal brain iron metabolism, cerebral white matter hypermetabolic activity, and genetic susceptibility. Furthermore, astrocytes, neurons, and glutamate abnormalities are prevalent in SCZ with abnormal lactate metabolism, which are essential components for maintaining ANLS in the brain. Therefore, an in‐depth study of the pathophysiological mechanisms of ANLS in SCZ with abnormal lactate metabolism will contribute to a better understanding of the pathogenesis of SCZ and provide new ideas and approaches for the diagnosis and treatment of SCZ. [ABSTRACT FROM AUTHOR]

Background and Aim: Up to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI‐resistant or refractory GERD. Vonoprazan, a potassium‐competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta‐analysis summarizes the efficacy and safety of vonoprazan for treating PPI‐resistant GERD (both erosive esophagitis [EE] and non‐erosive reflux disease [NERD]). Methods: Four electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI‐resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle‐Ottawa Scale (NOS) was used to assess study quality. Results: Twelve studies were included in this meta‐analysis. Healing rates of PPI‐resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8–94.8%) and 88.5% (95% CI 69.7–96.2%) at weeks 4 and 8, respectively. For healed PPI‐resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2–95.0%) at week 8, 86.0% (95% CI 72.1–94.7%) at week 24, and 93.8% (95% CI 69.8–99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8–81.7%) and 51.9% (95% CI 37.8–65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported. Conclusion: Vonoprazan demonstrated high efficacy in the healing and maintenance of PPI‐resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI‐resistant GERD patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Potassium‐competitive acid blockers more strongly suppress the gastric acid barrier than proton pump inhibitors and cause dysbiosis. However, preventive measures in this regard have not been established. We aimed to evaluate whether 1‐kestose, a known prebiotic, was effective at alleviating dysbiosis caused by potassium‐competitive acid blockers. Methods: Patients scheduled to undergo endoscopic resection for superficial gastroduodenal tumors were enrolled and randomized 1:1 to receive either 1‐kestose or placebo. All patients were started on potassium‐competitive acid blocker (vonoprazan 20 mg/day) and took 1‐kestose 10 g/day or placebo (maltose) 5 g/day for 8 weeks. The primary outcome was the effect of 1‐kestose on potassium‐competitive acid blocker‐induced alterations in the microbiome. The fecal microbiome was analyzed before and after potassium‐competitive acid blocker treatment via MiSeq (16S rRNA gene V3–V4 region). Results: Forty patients were enrolled, and 16 in each group were analyzed. In the placebo group, the Simpson index, an alpha diversity, was significantly decreased and relative abundance of Streptococcus was significantly increased by 1.9‐fold. In the kestose group, the Simpson index did not change significantly and relative abundance of Streptococcus increased 1.3‐fold, but this was not a significant change. In both groups, no adverse events occurred, ulcers were well healed, and pretreatment and posttreatment short‐chain fatty acid levels did not differ. Conclusions: The potassium‐competitive acid blocker caused dysbiosis in the placebo group; this effect was prevented by 1‐kestose. Thus, 1‐kestose may be useful in dysbiosis treatment. [ABSTRACT FROM AUTHOR]

Macromolecules are fragile when orally administered. An intestinal villi‐inspired metal–organic frameworks (MOFs)‐based smart pill with multiple advantages is developed to offer a salubrious solution for oral delivery of enzymes. In the pill, MOFs accommodate enzymes as carriers exhibit excellent in vitro and in vivo catalytic activities with good oral biosafety, displaying supreme protection from degradation or inhibition in simulated gastrointestinal tract and high tolerance in simulated gastric acid and intestinal fluid. Moreover, the bioinspired pill possesses the morphology of the small intestinal villi obtained via an in situ moulding strategy for enhancing biocatalysis, which is attributed to the increase of surface area. Collaboratively, the adhesive layer renders increased smart pill in vivo retention, which is verified in pigs, providing a clinically translational and versatile platform for long‐term oral macromolecule delivery. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co‐expression network analysis (WGCNA), construction of protein–protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC‐related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K‐Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein–ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Proton pump inhibitors (PPIs) are commonly used in the clinical treatment of abnormal gastric acid secretion and gastric acid related diseases. There are disputes about blood purification and PPIs reuse in patients with PPIs‐induced rhabdomyolysis. Herein we reported an 84‐year‐old woman with a 10‐year history of coronary heart disease and gastric acid. After 18 days of omeprazole therapy, the blood myoglobin of the patient rose progressively. Laboratory examination confirmed rhabdomyolysis, and PPIs‐induced rhabdomyolysis was considered. Atorvastatin was initially discontinued. Additionally, omeprazole was altered to iprazole. Since blood myoglobin continued to exceed the highest value identified, continuous renal replacement therapy (CRRT) and hemoperfusion (HP) were administrated. When PPIs‐induced rhabdomyolysis was considered, iprazole was discontinued. Two days after discontinuation of iprazole, blood myoglobin continuously decreased. After rhabdomyolysis was resolved, omeprazole was reused, and rhabdomyolysis did not reoccur. PPIs in combination with statins increase the risk of rhabdomyolysis. In the present case, switching to another PPIs or CRRT and HP therapy did not alleviate rhabdomyolysis. Rhabdomyolysis caused by statins is countless, but other reasons cannot be overlooked. In any case, the removal of etiology is the primary component of the treatment of rhabdomyolysis. When rhabdomyolysis is alleviated, PPIs can be reused safely under close monitoring. [ABSTRACT FROM AUTHOR]

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/CCK2 receptor (CCK2R) 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. [ABSTRACT FROM AUTHOR]

Nucleic acids (NAs) were recently shown to be digested by pepsin in vitro; however, NAs digestion in human gastric juice in vivo is more complicated because of the complex gastric environment and ingestion of other food components. The purpose of this study was to investigate the digestibility of NAs in real human gastric juices after ingestion of other food components. As a result, DNA digestion was not affected when carbohydrates, proteins, and metal elements were ingested within the recommended dietary intake levels. Separately, protein exerted an inhibitory effect on DNA digestion when the mass ratio of protein:DNA was greater than 40:1. DNA exists in the nucleoprotein, which is closer to the state of DNA in real food, and was digested efficiently in human gastric juice. Meanwhile, DNA digestion was rarely affected even when the concentrations of monovalent ion (Na+) and divalent ions (Mg2+) were as high as 500 and 100 mM, respectively, and high concentration of Mg2+ ranged from 20 to 100 mM accelerated the digestion. In particular, short‐stranded DNA (<100 nt) and miRNAs (19 ~ 25 nt) were not obviously degraded in human gastric juice. In conclusion, dietary NAs were digested efficiently and were not affected by other food components in human gastric juice, which may facilitate further digestion and utilization of DNA in the intestinal tract. [ABSTRACT FROM AUTHOR]

Keverprazan, a novel potassium‐competitive acid blocker, was approved for treating acid‐related diseases. This study aimed to analyze the safety, pharmacokinetics (PKs) and pharmacodynamics (PDs) of multiple doses of keverprazan. This was a randomized, positive‐/placebo‐controlled, phase Ic trial. Twenty‐six healthy adults were randomized to receive 20 mg/day keverprazan (n = 8), 40 mg/day keverprazan (n = 8), placebo (n = 6), or 20 mg/day vonoprazan (n = 4) for 7 days. Safety, PK and PD assessments were conducted. In the keverprazan, vonoprazan, and placebo groups, adverse events (AEs) were reported in nine (56.25%), two (50.00%), and three (50.00%) subjects, respectively. AEs were mild except a moderate abdominal pain leading to withdraw. No serious AEs occurred. The plasma concentration‐time profiles of keverprazan showed rapid absorption (median time to maximum plasma concentration of 1.25–3.0 h). The terminal half‐life was 6.23 and 7.01 h for keverprazan 20 and 40 mg groups on day 7. The maximum plasma concentration was 43.1 and 93.2 ng/mL, respectively. There was no apparent accumulation of keverprazan and the major metabolite after 7‐day administration. The intragastric pH greater than 5 holding time ratios (HTRs) over 24 h postdose increased from 79.1%, 84.4%, and 84.5% on day 1 to 99.0%, 97.4%, and 100.0% on day 7 in the vonoprazan 20 mg and keverprazan 20 and 40 mg groups, respectively. The intragastric pH greater than 5 HTR of keverprazan reached a plateau at 20 mg. Keverprazan is well‐tolerable. A steady‐state in exposure was generally reached after 7 days of treatment. A dose of 20 mg/day keverprazan can elicit a significant, stable, and long‐lasting gastric acid inhibition effect. [ABSTRACT FROM AUTHOR]

Aims: The new modified‐release formulation of tegoprazan, a novel potassium‐competitive acid blocker, is expected to improve the management of acid‐related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinations of tegoprazan with immediate‐release (IR) and delayed‐release (DR) formulations. Methods: A three‐cohort, open‐label, randomized, single‐dose, three‐treatment, six‐sequence, three‐period crossover study was conducted. Various combinations of tegoprazan IR and DR formulations (50, 75 or 100 mg) were administered orally once per period. The 24‐h intragastric pH was monitored before and after each administration. PK blood samples were collected for up to 48 h. PK and PD were compared among treatments. Results: Eighteen healthy Korean subjects completed the study. All treatment groups showed intragastric pH above 4 approximately 1 h following tegoprazan administration. Among the various combinations, the IR and DR combination at a 1:1 ratio induced greater gastric acid suppression (%Time pH ≥ 4) than IR alone in each dose group, both for 24 h (50 mg; 59% vs. 52%, P =.2188, 95% confidence interval [CI] −6.92–22.27, 100 mg; 85% vs. 70%, P <.05, 95% CI 8.92–22.19) and at night (50 mg; 27% vs. 16%, P =.1563, 95% CI −11.79–37.71, 100 mg; 77% vs. 49%, P <.05, 95% CI 16.14–42.98), with similar systemic exposure. Conclusions: The combinatorial tegoprazan in the IR and DR 1:1 ratio formulation was found to induce stronger gastric acid suppression throughout the day and at night, compared to the conventional IR formulation. [ABSTRACT FROM AUTHOR]

The article in the ANZ Journal of Surgery presents a surgical technique for managing chronic gastrocutaneous fistulas, which can be performed under local anesthesia. The procedure involves creating a circumferential incision around the fistula, thinning out the fibrous tract, and clipping it with Hem‐o‐lok or titanium Haemostatic clips. This approach has been successful in closing fistulas in all cases and is easily reproducible, making it a valuable option for surgeons dealing with such complications. [Extracted from the article]

The article "Pancreatic insufficiency after gastrectomy: an underdiagnosed condition?" published in the ANZ Journal of Surgery discusses the emergence of exocrine pancreatic insufficiency as a common issue post-gastrectomy, leading to symptoms like steatorrhea, bloating, and weight loss. The text highlights the challenges in diagnosing pancreatic insufficiency early on and emphasizes the importance of prompt recognition and treatment. Various factors contribute to the development of pancreatic insufficiency, such as the loss of gastric reservoir and vagal denervation. The article also explores the use of pancreatic enzyme replacement therapy (PERT) as a treatment option and the complexities involved in managing this condition effectively. [Extracted from the article]

This article discusses a case of severe caustic burns caused by gastric acid, which is a rare and unrecognized complication. An elderly female patient presented with symptoms of aspiration pneumonia and was found to have vesicles, blisters, and eroded areas on her skin. The burns were diagnosed as caustic skin burns due to prolonged contact with gastric juice. Treatment involved debridement, topical antiseptics, and wound dressings, with surgical debridement performed later. The article emphasizes the importance of recognizing and appropriately managing burns caused by gastric acid. [Extracted from the article]

A novel dual delayed‐release formulation (DR) of esomeprazole was developed to prolong the effect of esomeprazole inhibiting gastric acid secretion. This study investigated the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of DR esomeprazole. A randomized, open‐label, single‐dose, 2‐period, 2‐sequence crossover study was conducted in healthy Korean subjects. Subjects were orally administered a single dose of 40‐ mg DR esomeprazole in fasted and fed states in each period. PK and PD characteristics evaluated through continuous 24‐hour intragastric pH monitoring in fasted and fed states were compared between the 2 conditions. A total of 23 subjects completed the study and were included in the PK analysis. PD analysis was conducted in 21 subjects, excluding 2 subjects, because of inappropriate pH profiles. The systemic exposure of esomeprazole after a single dose of DR esomeprazole in the fed state decreased compared to that in the fasted state. However, the percentage decrease from baseline in integrated gastric acidity and the percentage of time at pH ≥4 were not significantly different between the 2 conditions. In conclusion, although the systemic exposure of esomeprazole decreased when DR esomeprazole was administered in the fed state compared to that in the fasted state, the degree of gastric acid secretion inhibition was not clinically different, regardless of food intake. [ABSTRACT FROM AUTHOR]

The beneficial effect of probiotics on host health is impaired due to the substantial loss of survivability during gastric transit caused by small intestinal enzymes and bile acids. Encapsulation helps to preserve the probiotics species from severe environmental factors. Lactobacillus paracasei, highly sensitive probiotic species to gastric acid, was encapsulated with polyacrylate resin. C57BL/6 male mice were equally divided into three groups; control group was fed with basal diet without any additives, the un‐encapsulated group was fed with 0.1% of a mixture of encapsulating material and L. paracasei, and encapsulated group was fed with 0.1% encapsulated L. paracasei (microcapsule) for 4 weeks. The result showed elevated fecal moisture percentage in the encapsulated group, but not in the un‐encapsulated group. Further study showed that the ratio of villus height to crypt depth in the small intestine was significantly higher compared to un‐encapsulated and the control group. Microencapsulated probiotics also remarkably increased intestinal mucin and secretory immunoglobulin A (sIgA) concentration, intestinal MUC‐2, and tight junction protein mRNA expression levels improving the intestinal barrier function of mice. In addition, microcapsules also reduced proinflammatory factor mRNA expression, while considerably increasing anti‐inflammatory factor mRNA expression. Microbiota metabolites, fecal LPS (Lipopolysaccharide) were downregulated, and acetate and lactate were upraised compared to control. Furthermore, glutathione peroxidase (GSH‐Px) and TAOC levels were increased and Malondialdehyde (MDA) was decreased improving antioxidant capacity. Microflora and bioinformatic predictive analysis of feces showed that encapsulated probiotics remarkably increased Lactobacillus proportions. Mice's intestinal health can thus be improved by using microencapsulated probiotics. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic‐based triple therapy is declining due to drug resistance development. Herein, a pH‐responsive reactive oxygen species (ROS) nanogenerator (Fe‐HMME@DHA@MPN) composed of acid‐responsive metal polyphenol network (MPN) shell and mesoporous metal‐organic nanostructure core [Fe‐HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton‐like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H2O2) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase‐like activity of the Fe‐HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H2O2. In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug‐resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self‐enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment of acid‐related disorders relies on gastric acid suppression. The percentage of time intragastric pH is >4 (pH >4 holding time ratio [HTR]) is important for healing erosive oesophagitis; and the pH >6 HTR is critical for eradication of Helicobacter pylori infection, as bacterial replication is active and antibiotic effectiveness is optimised. Vonoprazan, a potassium‐competitive acid blocker approved in the USA and other countries, suppresses gastric acid secretion in a predictable, rapid and consistent manner, extended over prolonged periods. Aim: To explore the relationship between vonoprazan exposure and pH HTR through a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: We pooled data from Phase 1 studies with intragastric pH measurements. Pharmacokinetic profiles were predicted for study participants using an existing population pharmacokinetic model. Pharmacokinetic and pharmacodynamic data were merged, and three direct‐link PK/PD models were derived and used to simulate pH HTRs with between‐participant variability for pH >4, >5 and >6, for vonoprazan doses of 20 mg once and twice daily. Results: We used data from five Phase 1 studies to derive the PK/PD model. These included 245 participants (95.1% male, 50.6% Japanese and 49.4% non‐Asian). Pre‐dose, the mean pH >4 HTR was 6.4%, pH >5 3.2% and pH >6 1.2%. After 7 days of dosing, simulations predicted pH >4 HTRs of 89.7% and 98.1%, and pH >6 HTRs of 53.1% and 75.3%, for vonoprazan 20 mg once and twice daily, respectively. Conclusions: Vonoprazan 20 mg once‐ and twice‐daily dosing demonstrated high, dose‐dependent, 24‐hour intragastric acid control in this PK/PD model, supporting clinical efficacy data in patients with acid‐related disorders. [ABSTRACT FROM AUTHOR]

Objectives: Glioma is one of the most aggressive brain tumours with poor overall survival despite advanced technology in surgical resection, chemotherapy and radiation. Progression and recurrence are the hinge causes of low survival. Our aim is to explain the concrete mechanism in the proliferation and progression of tumours based on tumour microenvironment (TME). The main purpose is to illustrate the mechanism of proton pump inhibitors (PPIs) in affecting acidity, hypoxia, oxidative stress, inflammatory response and autophagy based on the TME to induce apoptosis and enhance the sensitivity of chemoradiotherapy. Findings: TME is the main medium for tumour growth and progression. Acidity, hypoxia, inflammatory response, autophagy, angiogenesis and so on are the main causes of tumour progress. PPIs, as a common clinical drug to inhibit gastric acid secretion, have the advantages of fast onset, long action time and small adverse reactions. Nowadays, several kinds of literature highlight the potential of PPIs in inhibiting tumour progression. However, long‐term use of PPIs alone also has obvious side effects. Therefore, till now, how to apply PPIs to promote the effect of radio‐chemotherapy and find the concrete dose and concentration of combined use are novel challenges. Conclusions: PPIs display the potential in enhancing the sensitivity of chemoradiotherapy to defend against glioma based on TME. In the clinic, it is also necessary to explore specific concentrations and dosages in synthetic applications. [ABSTRACT FROM AUTHOR]

Background: The Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described. Methods: We analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups. Key Results: DGBI prevalence was similar in the French‐speaking and Dutch‐speaking population. Having one or more DGBI was negatively associated with psychosocial well‐being. The scores for depression were lower in the Dutch‐speaking participants with one or more DGBI compared to the French‐speaking participants. Interestingly, we also found significantly lower scores in the general Dutch‐speaking versus the French‐speaking population for depression and non‐gastrointesinal somatic symptoms, and higher global physical health and mental health quality‐of‐life component scores. In the Dutch‐speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non‐prescribed pain medication was higher in the French‐speaking group. Anxiety and sleep medication use was also higher in the latter group. Conclusions & Interferences: The results of this first in‐depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French‐speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI. [ABSTRACT FROM AUTHOR]

The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long‐term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP‐1366 affected gastric H+/K+‐ATPase activity and used the Na+/K+‐ATPase assay to confirm the selectivity of H+/K+‐ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP‐1366 and TAK‐438 were analyzed by Lineweaver–Burk. Also, we investigated the effects of JP‐1366 in various models involving reflux esophagitis. We found that JP‐1366 mediates strong, selective, and dose‐dependent inhibition of H+/K+‐ATPase. We found that JP‐1366 significantly suppressed gastric acid secretion in histamine‐treated pylorus‐ligated rats in a dose‐dependent manner. Additionally, we confirmed that JP‐1366 inhibited histamine‐stimulated gastric acid secretion in the HPD model. JP‐1366 exhibited a more than 2‐fold higher inhibitory effect on esophageal injury than TAK‐438 in GERD lesions and had a more potent inhibitory effect in indomethacin‐ or aspirin‐induced gastric ulcer rat models than TAK‐438. Additionally, JP‐1366 inhibited gastric ulcers. These results support the possibility that JP‐1366 is a good candidate drug for treating acid‐related diseases. [ABSTRACT FROM AUTHOR]

Aims: Gastric hypersensitivity (GHS) is a characteristic pathogenesis of functional dyspepsia (FD). DNA methyltransferase 1 (DNMT1) and acid‐sensing ion channel 1 (ASIC1) are associated with GHS induced by prenatal maternal stress (PMS). The aim of this study was to investigate the mechanism of DNMT1 mediating the analgesic effect of folic acid (FA) on PMS‐induced GHS. Methods: GHS was quantified by electromyogram recordings. The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected by western blot, RT‐PCR, and double‐immunofluorescence. Neuronal excitability and proton‐elicited currents of dorsal root ganglion (DRG) neurons were determined by whole‐cell patch clamp recordings. Results: The expression of DNMT1, but not DNMT3a or DNMT3b, was decreased in DRGs of PMS rats. FA alleviated PMS‐induced GHS and hyperexcitability of DRG neurons. FA also increased DNMT1 and decreased ASIC1 expression and sensitivity. Intrathecal injection of DNMT1 inhibitor DC‐517 attenuated the effect of FA on GHS alleviation and ASIC1 downregulation. Overexpression of DNMT1 with lentivirus not only rescued ASIC1 upregulation and hypersensitivity, but also alleviated GHS and hyperexcitability of DRG neurons induced by PMS. Conclusions: These results indicate that increased DNMT1 contributes to the analgesic effect of FA on PMS‐induced GHS by reducing ASIC1 expression and sensitivity. [ABSTRACT FROM AUTHOR]

As one of the five basic tastes, umami has the advantages of making the overall taste of food more harmoniously. Although various umami substances in food have been isolated and identified, in recent years, there are limit studies on the processing technology for improving food umami. Therefore, it is necessary to explore novel efficient umami improvement technologies to meet the urgentment of the food industry. This experiment was designed to study the effect of 0.1% (w/w) sodium bicarbonate (NaHCO3) combined with different power (0, 120, 180, 240, and 300 W) ultrasound treatment on the taste and flavor of chicken broth. Results demonstrated that the chicken broth under the power of 120 W ultrasound treatment combined with 0.1% (w/w) NaHCO3 was the most umami, and contained the largest amount of IMP. The chicken broth under the treatment of 180 W ultrasound combined with 0.1% (w/w) NaHCO3 has better flavor and sensory evaluation as the umami improved. In summary, 180 W ultrasound combined with 0.1% (w/w) NaHCO3 pretreatment is a simple and low‐cost processing technology, which is inclined to apply in industry. Practical Applications: Compared with the traditional umami improvement method, ultrasound can significantly reduce the cost of food umami‐enhancing with the characteristics of high safety, environmental protection, low operating cost, and high instantaneous efficiency. Sodium bicarbonate is an inorganic salt. Moderate intake is beneficial to the body. It can help neutralize stomach acid and supplement sodium for the body. In this study, low‐power ultrasound combined with low‐concentration of sodium bicarbonate solution was used to cook chicken soup, and the umami taste was improved to a large extent, which provided a novel method for industrial application. [ABSTRACT FROM AUTHOR]

Cholecystokinin (CCK) is a peptide family that functions pancreatic enzyme secretion, gallbladder contraction, intestinal motility, satiety, and stomach acid secretion. The CCK peptides are derived from pro‐CCK with a specific amino acid sequence (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) at their C‐terminus, where the Tyr residue is sulfated. The CCK peptides are ligands of the CCK receptors 1 (CCK1) and 2 (CCK2). In this study, we propose an approach for treating overweight and obese patients, preventing or reducing CCK1 activation using compounds that specifically interact with CCK peptides to regulate their interactions with CCK1. The compounds were selected by molecular docking using a chemical library with the selected residues (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) in CCK. Their effects were evaluated in a diet‐induced obese mice model. We show that compounds K2 and K5 decreased and maintained the body weight of the diet‐induced obese mice model, respectively, likely by preventing/hindering interactions between CCK peptides and CCK1, modifying its activity. This study demonstrates another approach to treating overweight and obesity by regulating CCK1 functions. The K2 and K5 compounds have properties supporting their continued development as new drugs against these risk factors. [ABSTRACT FROM AUTHOR]

Summary: Background: Zastaprazan (JP‐1366) is a novel potassium‐competitive acid blocker with favourable preclinical safety and efficacy profile being developed for the treatment of acid‐related diseases. Aims: To investigate the safety, tolerability, pharmacodynamics and pharmacokinetics of zastaprazan. Methods: A randomised, open‐label, placebo‐ and active‐controlled, single and multiple ascending dose clinical trial was conducted in healthy Korean male subjects. Intragatric pH and serum gastrin were measured to assess the pharmacodynamics, while serial blood and urine samples were collected to assess the pharmacokinetics. Pharmacogenomic evaluation was conducted to explore genetic variants, which can affect the pharmacodynamics and pharmacokinetics. Safety and tolerability including hepatotoxicity were evaluated. Results: Suppression of gastric acid secretion increased as the dose of zastaprazan increased. The percentage of time that gastric pH was over 4 (%Time pH >4) with zastaprazan 20 mg (85.19%) and 40 mg (91.84%) were similar to or greater than that with esomeprazole 40 mg (72.06%). Zastaprazan was rapidly absorbed within 2 h and eliminated with a half‐life of 6–10 h. Pharmacogenomic analysis found no genetic variant of drug metabolising enzymes including CYP2C19 or drug transporters associated with the exposure of zastaprazan. Zastaprazan was well tolerated with no clinically significant changes in safety and tolerability assessments. Conclusions: Zastaprazan was safe and well tolerated after a single oral dose up to 60 mg and multiple oral doses up to 40 mg. It also showed rapid, potent suppression of gastric acid secretion. Pharmacodynamic and pharmacokinetic profile of zastaprazan was suitable for treatment of patients with acid‐related diseases. [ABSTRACT FROM AUTHOR]

Summary: Background: Proton‐pump inhibitors (PPIs) are suspected to increase the risk of gastric cancer. Aim: To assess the risk of gastric cancer associated with the use of PPIs. Methods: We systematically searched Medline/PubMed, Embase and Scopus databases (until June 1, 2022) for randomised and non‐randomised studies (NRS) of the association between PPIs and gastric cancer having considered Histamine‐2 receptor antagonists (H2RAs) users as controls. We chose this comparison to minimise confounding by indication, and focus on patients requiring gastric acid suppression. Two authors independently extracted study data and assessed each study's risk of bias. Maximally‐adjusted relative risk (RR) estimates were extracted. Heterogeneity and small‐study effect were examined, and summary estimates were calculated using random‐ and fixed‐effect models. Stratified analyses and meta‐regression were employed to explore heterogeneity. We used GRADE to evaluate the certainty of evidence. Results: Of 8375 records, 12 NRS (>6 million patients; 11,554 gastric cancers) and two randomised clinical trials (498 patients; 1 gastric cancer) fulfilled the eligibility criteria. Randomised evidence was very imprecise and provided very‐low certainty evidence. Meta‐analysis of six NRS providing a comprehensive adjustment for confounding (2.5 million patients; 7372 gastric cancers) did not show any association between PPIs and gastric cancer (RRrandom = 1.07, 0.97–1.19; RRfixed = 1.05, 0.98–1.12). The certainty of the evidence was low. No convincing evidence of dose–response, or increased risk with long‐term use, was found. Lack of or minimal adjustment for confounding was associated with larger effect sizes. Conclusions: We found no association between PPIs and gastric cancer in NRS having adequately controlled for confounding. Published studies may suffer residual confounding. Systematic review registration: CRD42022335971. [ABSTRACT FROM AUTHOR]

Gastric ulcer is a deep hole in the stomach wall that penetrates the entire mucosa. About 10 % of the world population suffers from gastrointestinal tract disorders frequently known as gastric ulcers. Synthetic drugs are used to prevent gastric ulcers by suppressing the formation of gastric acid or stopping bacterial infections, however, these synthetic drugs have a number of harmful effects. Therefore, drug candidates with improved potency and minimal toxicity are crucial for the treatment and management of gastric ulcers. Recently, there has been a lot of interest in the medicinal potential of plants and their ability to treat gastric ulcers. There is an urgent need for herbal remedies to treat ulcers, and Aegle marmelos presents a better option due to scientifically proven antibacterial and antiulcer properties. In this context, A. marmelos highlights various benefits including anti‐inflammatory and antioxidant properties. It is well known that every component of A. marmelos has therapeutic and medical use. The two main causes of stomach ulcers are Helicobacter pylori and NSAIDs. A. marmelos shows strong antioxidant and antiulcer effects and guard against H. pylori‐caused ulcers on the stomach mucosa by inhibiting secretory factors and activating antioxidant processes. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first‐line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti‐vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real‐time reverse transcription‐polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER‐α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI‐induced increase in VEGF expression was counteracted by pharmacological ER‐α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti‐VEGF cancer chemotherapy. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Azurin as an electron transfer protein plays a vital role in the degradation of cancerous cells, but due to the destruction of its structure by stomach acid, finding safe and efficient techniques such as nano material to protect Azurin for drug delivery purposes is in high demand. In the present study, molecular dynamics techniques are exploited to examine the interaction and immobilization of Azurin on the surface of nanosheets such as graphene monoxide, silicon carbide and boron nitride at 310 K. To analyze the simulation results, structural parameters such as root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (Rg), the distance between the center of mass of immobilized protein and surface of the considered nanosheets, and surface accessible solvent area (SASA) are measured. Additionally, the interaction energy of the protein with the nanosheet surface is investigated using structural and energetic parameters of the protein and nanosheets including residue polarity, charge density, hydrophilicity, and hydrophobicity. The simulation results exhibit the adsorption and immobilization of Azurin on the targeted surfaces while maintaining its native structure. As an initial step, these results reveal a promising potential application of studied nanosheets in aqueous condition for the smart delivery, medicine and cancer therapy of Azurin. [ABSTRACT FROM AUTHOR]

The pH‐responsive nanoparticles are a promising drug‐carrier because they always showed sensitivity and specificity to the pH changes caused by the surrounding environment. Most of the therapeutic drugs are generally absorbed in the stomach and small intestine due to the pH‐responsive nanoparticles always release the cargos at acidic media, making them difficult to reach the lower part of the large intestine, as well as inhibiting the therapeutic effects. Herein, an alkaline media‐sensitive supramolecular nanoparticle, regarded as SACD/PEI NPs, is prepared. SACD/PEI NPs exhibit assemble/disassemble state by changing the pH, which is used to encapsulate the anti‐colon drug CSL. CSL@SACD/PEI NPs showed a high release rate of 86.1% for the encapsulated CSL at pH = 8.5 (mimic the colon micro‐environment), while keeping stable at pH = 1.2 (mimic the gastric acid micro‐environment). Meanwhile, CSL@SACD/PEI NPs exhibited low hemolysis, indicating they possess good biocompatibility. In cell experiments, CSL@SACD/PEI NPs had a similar inhibitory effect on colon tumor cell SW480 and showed low cytotoxicity to normal cells compared with free CSL. Furthermore, both free CSL and CSL@SACD/PEI NPs showed excellent apoptosis effects on tumor cell SMMC‐7721. We hope that CSL@SACD/PEI NPs could be the valuable base‐answered drug delivery candidate, and have potential application for colon tumor therapy. [ABSTRACT FROM AUTHOR]

Traditional fermented products and human intestines are rich sources of Lactobacillus strains which may have remarkable probiotic properties. In the present study, the probiotic properties of 40 Lactobacillus strains isolated from intestinal tracts of longevity population and traditional fermented food in China were determined, including the survival rates in simulated gastric acid and bile salt, aggregation, hydrophobicity, adhesion rate, antioxidant ability (ferric reducing antioxidant power), and antimicrobial ability. The differences between human strains and nonhuman strains were compared via t‐test and principal component analysis (PCA). The significant differences were found in the survival rate at 0.3% bile salt, adhesion ability of the strains, and antioxidant ability of the fermentation broth (p <.05). The results of PCA showed that the first principal component (PC1) score of human strains was significantly higher than that of nonhuman strains (p <.01). And some probiotic Lactobacillus were selected for further application based on the unsupervised clustering algorithm, heat‐map analysis, and K‐means algorithm. Four strains, CS128, CS39, CS01, and CS1301, along with Lactobacillus rhamnosus GG (LGG) were divided into cluster I. The four strains, all isolated from human tracts, have been selected. Thus, human Lactobacillus has better probiotic potential and application prospects than strains from the nonhuman source. PCA, the unsupervised clustering algorithm, and heat‐map analysis can be used to analyze and select Lactobacillus visually and effectively. [ABSTRACT FROM AUTHOR]

Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP‐5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH‐dependent, thus the drug–drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open‐label, fixed‐sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least‐squares (LS) mean ratios of ripretinib area under the concentration–time curve from 0 to ∞ (AUC0–∞) and maximum observed concentration (Cmax) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC0–∞ and Cmax were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers. [ABSTRACT FROM AUTHOR]

Background and Aim: The influence of gastric acid inhibitors (GAIs) on nonsteroidal anti‐inflammatory drug (NSAID)‐induced enteropathy is controversial. Herein, the influences of different GAIs on NSAID‐induced intestinal injury and the underlying mechanisms are clarified. Methods: Indomethacin (IND; 10 mg/kg/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora. Results: Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND‐induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5‐day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that Lactobacillus was significantly increased in the groups of OPZ, IPZ, and VPZ, while Bacteroides was significantly increased in the RPZ group. Conclusion: Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND‐induced intestinal damage model seem different. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) reliably suppress gastric acid secretion and are therefore the first‐line treatment for gastric acid‐related disorders. Hypomagnesemia (serum magnesium [Mg2+] <0.7 mmol/L) is a commonly reported side effect of PPIs. Clinical reports demonstrate that urinary Mg2+ excretion is low in PPI users with hypomagnesemia, suggesting a compensatory mechanism by the kidney for malabsorption of Mg2+ in the intestines. However, the exact mechanism by which PPIs cause impaired Mg2+ absorption is still unknown. In this review, we show that current experimental evidence points toward reduced Mg2+ solubility in the intestinal lumen. Moreover, the absorption pathways in both the small intestine and the colon may be reduced by changes in the expression and activity of key transporter proteins. Additionally, the gut microbiome may contribute to the development of PPI‐induced hypomagnesemia, as PPI use affects the composition of the gut microbiome. In this review, we argue that the increase of the luminal pH during PPI treatment may contribute to several of these mechanisms. Considering the fact that bacterial fermentation of dietary fibers results in luminal acidification, we propose that targeting the gut microbiome using dietary intervention might be a promising treatment strategy to restore hypomagnesemia in PPI users. [ABSTRACT FROM AUTHOR]

Aims: Nocturnal acid breakthrough has been considered an unmet need of proton‐pump inhibitors. Tegoprazan, a novel potassium‐competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night‐time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid‐suppressive effects. Methods: A randomized, open‐label, 3‐period, 6‐sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing. Results: Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night‐time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night‐time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes. Conclusion: Tegoprazan produced more rapid, potent and well sustained night‐time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of a single intramuscular adminsitration of long‐acting omeprazole (LA‐OMEP) in increasing gastric pH in dogs. Hypothesis: We hypothesized that LA‐OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration. Animals: Nine healthy research dogs. Methods: Prospective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA‐OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined. Results: The mean onset of action for the LA‐OMEP was 98.11 min (SD 46.39). The mean number of days the dogs' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3‐7) and 5.25 days for MPT pH ≥4 (range, 3‐7). Long‐acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs. Conclusions and Clinical Importance: The LA‐OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed. [ABSTRACT FROM AUTHOR]

Hydrogel microspheres with probiotic‐loaded therapy have been considered an effective and safe strategy for treating inflammatory bowel disease (IBD). However, the low survival rate under harsh stomach conditions and inflam‐matory cytokine target release efficiency remains a major challenge for their application. Herein, a novel NO‐responsive poly‐γ‐glutamic acid (γ‐PGA) hydrogel microcapsule (NRPM) strategy based on a droplet microfluidic technology platform is proposed. Accordingly, highly uniform microspheres with high cell densities (6.0 × 108 cells mL−1) and a wide range of diameters (100–600 μm) are produced, which are critical for realizing accurate down‐stream evaluation and applications. Owing to the cytoprotective effects of the NRPM, the decorated probiotics showed high viability in the simulated gastric (89.67%) and intestinal (93.67%) fluid environments, while the data are 0% and 61.60% for free cells, respectively. Moreover, both in vitro and in vivo studies demonstrate that microspheres can respond to nitric oxide (NO) stimuli and rapidly release probiotics to maintain the intestinal mechanical barrier and regulate the balance of intestinal flora. Consequently, NRPM significantly increases the treatment efficacy against dextran sulfate sodium‐induced colitis in a mouse model. The results demonstrate that NRPM is a promising approach for improving the efficacy of orally administered probiotics in patients with colonic IBD. [ABSTRACT FROM AUTHOR]

Background: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. Materials and Methods: This nationwide, multicenter, cross‐sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow‐up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. Results: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth‐containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1–2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. Conclusions: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future. [ABSTRACT FROM AUTHOR]

Background and Aim: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post‐ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post‐ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. Methods: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post‐ESD bleeding. Results: There were 3935 H. pylori‐positive patients and 4235 H. pylori‐negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post‐ESD bleeding in H. pylori‐negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori‐positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori‐negative, but not H. pylori‐positive, patients, the rate of post‐ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. Conclusions: Nonsevere gastric mucosal atrophy was a risk factor for post‐ESD bleeding in early gastric cancer in H. pylori‐negative patients but not in H. pylori‐positive patients. [ABSTRACT FROM AUTHOR]

Retrospective data suggest that gastric acid reduction by proton pump inhibitors (PPIs) impairs the dissolution and subsequent absorption of capecitabine, and thus potentially reduces the capecitabine exposure. Therefore, we examined prospectively the effect of esomeprazole on the pharmacokinetics of capecitabine. In this randomized crossover study, patients with cancer were assigned to 2 sequence groups, each consisting of 3 phases: capecitabine with esomeprazole administration 3 hours before (phase A), capecitabine alone (phase B), and capecitabine concomitant with cola and esomeprazole co‐administration 3 hours before (phase C). The primary end point was the relative difference (RD) in exposure to capecitabine assessed by the area under the plasma concentration‐time curve from zero to infinity (AUC0‐inf) and analyzed by a linear mixed effect model. Twenty‐two evaluable patients were included in the analysis. After esomeprazole, there was a 18.9% increase in AUC0‐inf of capecitabine (95% confidence interval (CI) −10.0% to 57.0%, P = 0.36). In addition, capecitabine half‐life was significantly longer after esomeprazole (median 0.63 hours vs. 0.46 hours, P = 0.005). Concomitant cola did not completely reverse the effects observed after esomeprazole (RD 3.3% (95% CI −16.3 to 27.4%, P = 1.00). Capecitabine exposure is not negatively influenced by esomeprazole cotreatment. Therefore, altered capecitabine pharmacokinetics do not explain the assumed worse clinical outcome of PPI‐cotreated patients with cancer. [ABSTRACT FROM AUTHOR]

Fifty‐seven strains of Lactobacillus were isolated from fecal samples of healthy young people in Tibet, Xinjiang, and Inner Mongolia using pure culture methods. Lactobacillus ruminis and Lactobacillus gasseri were the dominant Lactobacillus species isolated from the intestinal microflora, accounting for 54.4% and 14.0% of the total isolates, respectively. Isolated strains were identified by 16S rRNA sequencing, and their tolerance to gastric acid and bile salt, and fermentation characteristics were evaluated. The results of experiments in vitro showed that nine of the isolated strains of Lactobacillus grew well at pH 3.0. After 11 h of incubation in artificial digestive juices, the isolated L. plantarum and the control strain L. plantarum P8 still had high survival rates. Most of the isolates and control isolates have strong tolerance to bile salts. The evaluation of fermentation characteristics indicated that the ability of the intestinal Lactobacillus to ferment skimmed milk was lower than that of the reference L. plantarum P8. In the process of storage, the viable count of screened isolates of human origin in fermented milk decreased to some extent, but remained above 7.01 ± 0.22 log CFU/ml, showing good storage characteristics. [ABSTRACT FROM AUTHOR]