Background/Objectives: HF33 is a polyherbal formulation developed from Thai folk medicinal knowledge for the management of dyspepsia and gastric ulcer-like symptoms. Its gastroprotective activity and underlying mechanisms have not been systematically investigated. This study aimed to characterize the HF33 formulation and evaluate the gastroprotective activity, possible mechanisms of action, and acute oral toxicity of its ethanolic extract. Methods: HF33 formulation powder was characterized according to the Thai Herbal Pharmacopoeia using pharmacognostic, physicochemical, and HPLC-PDA analyses, and the extract was chemically fingerprinted by compact mass spectrometry. Antioxidant activity and total phenolic and flavonoid contents were determined. Gastroprotective activity of the extract (150, 300, and 600 mg/kg, p.o.) was evaluated in male Sprague-Dawley rats using restraint water immersion stress-, indomethacin-, and acidified ethanol (EtOH/HCl)-induced gastric ulcer models. Histopathology, MDA and SOD, gastric mucus content, and gastric secretion parameters were assessed. Acute oral toxicity was evaluated in female Sprague-Dawley rats according to OECD Test Guideline 420. Results: Quality characterization established the identity and quality attributes of the HF33 formulation and its extract prior to biological evaluation. The HF33 extract exhibited in vitro antioxidant activity and significantly reduced gastric lesion formation in all three ulcer models. Gastroprotection was associated with preservation of gastric mucosal architecture, increased gastric mucus content, reduced MDA levels, and restored SOD activity, without significant alteration of gastric secretion parameters. No treatment-related toxicity was observed following a single oral administration of 2000 mg/kg. Conclusions: The HF33 ethanolic extract exhibited gastroprotective activity across multiple experimental gastric ulcer models. The protective activity was associated with preservation of mucosal integrity, enhancement of the mucus barrier, and attenuation of oxidative damage without affecting gastric acid secretion. These findings support further preclinical investigation of HF33 as a quality-characterized polyherbal formulation with potential gastroprotective properties.

Background and Objectives: Functional dyspepsia (FD) is a heterogeneous disorder of gut-brain interaction with a multifactorial pathophysiology. Although Helicobacter pylori infection has been implicated in FD, its relationship with Rome IV FD subgroups and the extent to which successful eradication results in sustained symptomatic improvement remain unclear. This study aimed to evaluate the distribution of H. pylori infection across Rome IV FD subgroups and to assess long-term symptomatic response following successful eradication. Materials and Methods: This prospective, single-center observational cohort study included patients with dyspeptic symptoms who underwent evaluation according to the Rome IV criteria. Adult patients who completed the Rome IV gastroduodenal symptom questionnaire and underwent upper gastrointestinal endoscopy were evaluated. Patients fulfilling the Rome IV criteria for FD without an organic cause explaining their symptoms were classified as postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), or overlapping PDS-EPS. H. pylori status was determined histopathologically using gastric antral and corpus biopsies. H. pylori-positive patients received 14-day bismuth-based quadruple therapy, and eradication was assessed using a stool antigen test 8-12 weeks after treatment. Symptomatic response was evaluated at month 2, 6, and 12 using Likert scale and clinical assessment. Results: Of 425 patients evaluated, 244 fulfilled the Rome IV criteria for FD, and 127 (52.0%) were H. pylori positive. The prevalence of H. pylori infection differed significantly among the Rome IV FD subgroups (p < 0.001) and was highest in the EPS subgroup (73.4%, 58/79), compared with the PDS (37.7%, 40/106) and overlapping (49.2%, 29/59) subgroups. H. pylori positivity was significantly higher in EPS than in both PDS and overlapping subgroups (p < 0.001 and p = 0.003, respectively). First-line eradication rates were 96.4% (106/110) per protocol and 83.5% (106/127) by intention to treat. Symptomatic response rates following successful eradication were 43.4% (46/106), 60.4% (64/106), and 70.2% (66/94) at month 2, 6, and 12, respectively, compared with 47.0% (55/117), 63.4% (71/112), and 78.4% (80/102) in H. pylori-negative patients. Between-group differences in symptomatic response were not statistically significant (p = 0.58, 0.64, and 0.18, respectively). In the conservative sensitivity analysis, month 12 response was lower in the H. pylori-positive cohort (55.1% vs. 68.4%, p = 0.03). Sustained complete symptom resolution occurred in 25.5% (24/94) of patients after successful eradication and 19.6% (20/102) of H. pylori-negative patients (p = 0.32). Conclusions: H. pylori infection was significantly more prevalent in the EPS phenotype, supporting the biological heterogeneity of Rome IV functional dyspepsia. Sustained complete symptom resolution occurred in 25.5% after successful eradication and 19.6% in the H. pylori-negative cohort. Despite successful eradication in 96.4% per protocol and 83.5% by intention to treat, no clear symptomatic advantage over the H. pylori-negative cohort was demonstrated. Differences in phenotype distribution, treatment exposure, and follow-up completeness limit direct comparisons and preclude conclusions of equivalence or attribution of symptom resolution to eradication alone.

Background/Objectives: Proton pump inhibitors (PPIs) are widely used, but real-world utilisation data from internal medicine settings remain limited. We estimated the screening-period prevalence of self-reported current PPI use among attendees of two internal medicine outpatient clinics and described treatment patterns among current users. Methods: In this single-centre cross-sectional survey in Adana, Türkiye (August 2025-January 2026), 977 consecutively screened adult outpatients were asked about current PPI use; 178 reported current use, and 149 of them (83.7%) completed an investigator-administered questionnaire. Wilson 95% confidence intervals (CIs) were calculated for the prevalence and three prespecified proportions; exploratory ≤6-versus > 6-month comparisons used exact tests with Holm adjustment. Results: Current use was reported by 178/977 outpatients (18.2%; 95% CI 15.9-20.8%). Among users (mean age 57.5 ± 13.6 years; 61.1% women), median reported duration was 54 months (interquartile range 18-84); 86.6% reported use for >6 months and 34.2% for >5 years. Pantoprazole was most common (31.5%). Gastroprotection during non-steroidal anti-inflammatory drug (NSAID) or antithrombotic therapy (45.0%) and dyspepsia (35.6%) were the leading reasons; 80.6% of those citing gastroprotection reported current NSAID or antithrombotic use. Ongoing upper-gastrointestinal symptoms were reported by 77.9% (59.7% of those citing gastroprotection; 100.0% of those citing reflux). Conclusions: Nearly one in five screened outpatients reported current PPI use, and reported exposure was predominantly prolonged. Ongoing symptoms and prolonged use without a documented indication are signals that should prompt structured, individualised medication review.

Background: The association between Helicobacter pylori and the resident gastric microbiota plays a critical role in gastric carcinogenesis; however, the specific microbial alterations accompanying the transition from chronic inflammation to malignancy remain to be fully elucidated. This study aimed to characterize the distinct bacterial signatures associated with gastric cancer (GC) and non-ulcer dyspepsia (NUD) within a Turkish cohort, evaluating these structural shifts in the context of the "hit-and-run" hypothesis. Methods: Genomic DNA was isolated from 158 gastric biopsy specimens obtained from 96 individuals stratified into four homogeneous groups based on clinical H. pylori status and histopathological presentation: H. pylori-positive GC (Hp+GC, n = 37), H. pylori-negative GC (Hp-GC, n = 25), H. pylori-positive NUD (Hp+NUD, n = 17), and H. pylori-negative NUD (Hp-NUD, n = 17). Next-generation amplicon sequencing targeting the V3-V4 hypervariable regions of the 16S rRNA gene was executed, followed by strict quality filtering via the DADA2 pipeline and taxonomic classification against the SILVA database. Results: Alpha diversity analysis demonstrated a significant reduction in microbial richness and evenness within the Hp+GC group compared with all other cohorts (FDR-adjusted q < 0.001). Beta diversity metrics revealed distinct ecological trajectories, with the overall microbial community structure of the Hp+GC group diverging sharply from non-malignant controls. Taxonomic profiling unveiled a profound dysbiotic shift in the Hp+GC microenvironment, characterized by a massive depletion of the Firmicutes phylum and a concomitant overrepresentation of Proteobacteria (66.56%). While the Helicobacter genus predominated in the non-malignant Hp+NUD group, its relative abundance declined to negligible levels (<0.01%) in biopsy samples of gastric cancer patients, despite clinical positivity. This malignant niche was instead robustly invaded by potentially pathogenic bacteria belonging to the Enterobacteriaceae family, showing highly significant enrichment of Morganella (11.14% mean relative abundance; FDR-adjusted q < 0.001), Providencia (3.43%; FDR-adjusted q < 0.001), and Klebsiella (2.03%; FDR-adjusted q < 0.001). Conclusions: These findings support the "hit-and-run" model, indicating that H. pylori acts as an initiator of carcinogenesis but is progressively outcompeted by an aggressive, nitrate-reducing, and pro-inflammatory Enterobacteriaceae-dominated dysbiotic bacterial community as mucosal atrophy and hypochlorhydria neutralize the typical acidic gastric barrier.

Arterial thrombosis is a rare but potentially life-threatening complication of acute pancreatitis, with poorly defined clinical characteristics. This paper presents a case of extensive large-artery thrombosis complicating acute interstitial edematous pancreatitis along with a literature review. A 61-year-old man with acute interstitial edematous pancreatitis superimposed on chronic pancreatitis underwent contrast-enhanced computed tomography four weeks after the initial presentation because of persistent dyspepsia. The imaging revealed pancreatic pseudocysts and extensive arterial thrombosis involving the thoracic and abdominal aorta, bilateral internal iliac arteries, and the left subclavian artery. The patient was treated with systemic anticoagulation, resulting in radiologic resolution. A literature review identified 11 previously reported cases of acute pancreatitis-associated arterial thrombosis. Including the present case (n=12), five cases occurred in interstitial edematous pancreatitis, while seven developed in acute necrotizing pancreatitis. The aorta and major visceral arteries were the most frequently involved vessels. Arterial thrombosis was detected within the first week in seven cases, whereas five cases were diagnosed later, including one as late as 60 days. Arterial thrombosis can occur in necrotizing and interstitial pancreatitis and may present either early or later in the disease course. Awareness and timely imaging may facilitate prompt recognition and management.

Acupoint sticking therapy (AST) is a traditional Chinese transdermal treatment widely used for chronic conditions such as asthma and dyspepsia. Despite its clinical efficacy, the material basis of AST, particularly the penetration dynamics of its active transdermal components, remains unclear, hindering further investigation into its therapeutic mechanisms. This study developed an integrated platform combining in vivo microdialysis with GC-Orbitrap-HRMS to characterize transdermal components and penetration profiles of AST, using the Jianpi Patch (JPT) as a model due to its proven efficacy in pediatric functional dyspepsia. Firstly, 204 volatile compounds in JPT were identified, including terpenoids, hydrocarbons, esters, ketones and alcohols. Furthermore, through real-time microdialysis at the Shenque (CV8) acupoint in rats, 66 compounds were identified as transdermal constituents by GC-Orbitrap-HRMS. Based on their transdermal profiles, these penetrating components were categorized into three distinct patterns: rapid penetration (peak within 1-2 h), delayed peak (gradual increase, maximum at 3-4 h), and sustained release (progressive rise, peak at 5-6 h). This work established a minimally invasive platform for screening the material basis of transdermal herbal formulations and provided new insights into the permeation behavior of AST.

Alpha-GAL syndrome (AGS) is a type of allergy to mammalian meat and other foods or pharmaceuticals made from mammalian substrates. It is an IgE-mediated reaction caused by sensitization to the polysaccharide galactose-α-1,3-galactose (alpha-GAL) found in tick saliva after a previous tick bite. Alpha-GAL is present on proteins of mammals except primates. Sensitization to alpha-GAL in tick saliva predisposes to cross-reactivity following exposure (oral or non-oral) to glycated galactose-α-1,3-galactose proteins, regardless of their origin. Symptoms of varying severity (from dyspepsia to anaphylaxis) appear 3-6 h after exposure (delayed hypersensitivity) and are usually in the presence of a cofactor. Due to the unusual mechanism and source of allergy, the diagnosis of AGHS is difficult and long-lasting. It is estimated that it takes an average of 7 years from the appearance of the first symptoms to the diagnosis of AGS. Diagnostic procedures include a review of the patient's clinical history, a physical examination, and additional tests, such as alpha-GAL-specific immunoglobulin E (sIgE) or, optionally, a basophil activation test (BAT) with alpha-GAL. Alpha-GAL sIgE levels can be measured using screening methods (ImmunoCAP ISACE112i or ALEX3) and the quantitative ImmunoCAP method (ThermoFisher Scientific), which is the reference method. Adherence to appropriate diagnostic procedures and careful analysis of clinical data and additional test results is an effective tool for diagnosing AGS and implementing appropriate therapeutic strategies.

Contraction of both striated and smooth muscles is regulated by intracellular Ca[2+] signals. The mechanisms of contraction following the Ca[2+] signal are significantly different between striated and smooth muscles. The Ca[2+]-dependent reversible phosphorylation of the 20 kDa myosin light chain plays an essential role in regulating smooth muscle contraction. The phosphorylation theory of smooth muscle contraction was proposed in the mid-1970s. In the late 1980s, quantitative evaluation of cytosolic Ca[2+] concentrations and contraction revealed that the contraction was not always associated with changes in cytosolic Ca[2+] concentrations. G protein-coupled receptor agonists generally produce a greater contraction at a certain level of Ca[2+] than membrane depolarization. Consequently, the concept of dual regulation, in which smooth muscle contraction is regulated by not only Ca[2+] signals but also myofilament Ca[2+] sensitivity, was established. The identification of smooth muscle myosin light chain phosphatase in the early 1990s greatly facilitated the understanding of the molecular mechanisms regulating myofilament Ca[2+] sensitivity over the following 10 years. The overall picture of the mechanisms of smooth muscle contraction became clearer by the early 2000s. Smooth muscle research is ready to open a new horizon of translational research aimed at precision medicine for smooth muscle diseases, such as hypertension, asthma, and dyspepsia. The present review article overviews the history of research on smooth muscle contraction and summarizes the current understanding of the mechanisms of smooth muscle contraction, focusing on the regulation of myosin light chain phosphatase and myofilament Ca[2+] sensitivity.