mosapride + rebamipide (MotiReb / Mucosta + Gasmotin / MR tablet)

[Efficacy and safety of H. pylori eradication therapy in real-world clinical practice: results of the «PAMIR» observational program].

Alexeev N Y NY, Astaf'eva T O TO, Vishnevskaya V V VV, Donchenko N D ND et al.

To evaluate the efficacy, safety and impact on gastrointestinal symptoms of Helicobacter pylori eradication therapy with a ready-to-use set of tablets and capsules [omeprazole 20 mg × 2, clarithromycin 500 mg × 2, amoxicillin 500 mg × 4] (Pylobact® AM) in duodenal ulcer patients within the framework of an observational program. 912 H. pylori-positive patients were included (404 men and 508 women, average age - 43.8 years (43.82±11.39; 18-64 years). Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire; patients assessed treatment satisfaction, and physicians assessed treatment efficacy and tolerability using a five-point Likert scale. The efficacy of H. pylori eradication was assessed using the results of the 13C-urea breath test, H. pylori antigen stool test, or a rapid urea test with biopsies of the gastric body and antrum obtained during upper endoscopy. A total of 870 patients completed the observational program: 538 patients in the standard triple therapy group (PAM group) and 332 patients in the group enhanced with a bismuth preparation, rebamipide, and/or a probiotic (PAMplus group). A subgroup of patients received triple therapy with bismuth and the synbiotic complex of Floriose with probiotic strains Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, Bifidobacterium lactis Bl-04, inulin and B vitamins. H. pylori eradication rates in the PAM, PAMplus, and PAM+Bi+F (ITT) groups were 90.6, 97.03, and 96.82%, respectively. Treatment significantly reduced GSRS abdominal pain scores. Physicians rated the treatment efficacy and tolerability as "very good" or "good" at the end of the program in 93.3% of patients. Patients rated 93.68% as completely or mostly satisfied with the treatment. The effectiveness of H. pylori eradication with a ready-to-use set of capsules and tablets for standard triple therapy is ensured by high patient compliance. The combination of standard triple therapy with bismuth, probiotics, and/or rebamipide increases treatment efficacy.

Retraction notice to "Rebamipide protects against experimentally induced intestinal ischemia/reperfusion-promoted liver damage: Impact on SIRT1/β-catenin/FOXO1and NFκB signaling" [Int. Immunopharmacol. 119 (2023) 110269].

Elwany Nisreen E NE, Salem Amal El AE, Mohamed Noura Mostafa NM, Khalil Sama S SS et al.

Mosapride promotes internalization of a TREK1-HTR4 complex and exerts rapid antidepressant-like effects.

Lee Soomin S, Kim Seung Chan SC, Noh Junyeol J, Seo Gyunghwa G et al.

Major depressive disorder (MDD) remains a critical global health burden, and a substantial proportion of patients exhibit insufficient responses to conventional monoaminergic antidepressants. Selective inhibition of the two-pore domain potassium channel TREK1 has emerged as a promising antidepressant strategy; however, the regulatory mechanisms controlling TREK1 trafficking-particularly its functional coupling with G protein-coupled receptors (GPCRs)-remain poorly understood. Here, we established a cell-based screening platform using a biomolecular luminescence complementation (BiLC) assay to monitor agonist-induced changes in membrane-associated TREK1. Using this platform, we identified a TREK1-5-hydroxytryptamine receptor 4 (HTR4) complex in vitro and in native hippocampal tissues using biomolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP), and proximity ligation assays (PLA). Live-cell imaging demonstrated that treatment with the HTR4 agonist mosapride induces redistribution/internalization of a plasma membrane-associated TREK1-HTR4 pool into intracellular compartments. Electrophysiological recordings further confirmed that mosapride reduces TREK1 channel activity in an HTR4-dependent manner. In vivo, oral administration of mosapride for five days ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and preserved markers associated with hippocampal neurogenesis. Notably, viral expression of the TREK1 C-terminal interaction domain (C1), which competitively disrupts the TREK1-HTR4 complex, attenuated the neurogenic and behavioral effects of mosapride, supporting a causal role of TREK1 regulation in mediating these antidepressant-like actions. Collectively, our findings reveal a previously unrecognized mechanism in which HTR4 dynamically regulates TREK1 trafficking and function, and they highlight GPCR-based modulation of TREK1 as a potential therapeutic strategy for depressive disorders.

Clinical efficacy and gastrointestinal hormonal effect of Lactobacillus rhamnosus combined with lactulose for treatment of irritable bowel syndrome with constipation.

Wu Rongfang R, Pan Jindun J

This study aimed to explore the clinical efficacy of Lactobacillus rhamnosus combined with lactulose for the treatment of irritable bowel syndrome with constipation (IBS-C) and its effect on gastrointestinal hormones. A prospective, randomized, double-blind trial was conducted with three groups: control (n=45, mosapride citrate tablets), monotherapy (n=44, lactulose + control regimen), and combination (n=45, Lactobacillus rhamnosus + monotherapy regimen). The primary outcome measure was clinical efficacy. Secondary outcomes included the Bristol Stool Scale (BSS), Irritable Bowel Syndrome Quality of Life Score (IBS-QoL), Perceived Stress Scale (PSS), Irritable Bowel Syndrome Severity Score (IBS-SSS), gut microbiota, and gastrointestinal hormones assessed at days 0, 28, and 56, along with safety observations. Following a 56-day intervention period, the combination group achieved 100.00% clinical effectiveness, significantly higher than the monotherapy (93.18%) or control groups (75.56%). Fecal consistency responders were 84.44% in the combination group vs. 47.73% (monotherapy) and 28.89% (control). The combination group showed higher IBS-QoL scores, lower PSS scores, and reduced IBS-SSS scores (P < 0.05). Intestinal flora analysis revealed decreased Ruminococcaceae and increased Fibrobacteraceae and Campylobacteraceae in the combination group. Gastrointestinal hormones improved, with increased motilin and decreased vasoactive intestinal peptide (P < 0.05). There was no significant difference in the incidence of adverse events among the three groups (P > 0.05). Lactobacillus rhamnosus combined with lactulose significantly improves IBS-C symptoms and quality of life, and positively modulates intestinal flora and gastrointestinal hormones.