Overexpression of HSP27 accelerates stress-induced gastric ulcer healing via the CXCL12/CXCR4 axis.

Chronic stress often triggers gastrointestinal complications, including gastric injury and ulcers. Understanding the role of heat shock protein 27 (HSP27) in stress-induced gastric ulcers could unveil novel therapeutic targets. Here, we established a stress-induced gastric ulcer rat model using water immersion restraint stress and administered adenovirus-packaged HSP27 overexpression vector. Gastric ulcer severity was scored, and mucosal changes were assessed. Gastric epithelial and endothelial cells were treated with lipopolysaccharide and transfected with HSP27 overexpression vectors to evaluate cell viability, migration and angiogenesis. Expression levels of HSP27, C-X-C motif chemokine ligand 12 (CXCL12) and C-X-C motif chemokine receptor 4 (CXCR4) were measured in tissues and cells. HSP27 expression was initially low during stress-induced gastric ulceration but increased during ulcer healing. HSP27 overexpression accelerated ulcer healing in rats, promoting gastric epithelial cell proliferation and migration and gastric endothelial cell angiogenesis through the CXCL12/CXCR4 axis. Inhibitor IT1t reversed the effects of HSP27 overexpression on cell proliferation, migration and angiogenesis. In summary, HSP27 overexpression facilitated ulcer healing, which was partially mediated by the CXCL12/CXCR4 axis.

Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis.

BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.

Ipomoea carnea mitigates ethanol-induced ulcers in irradiated rats via Nrf2/HO-1 pathway: an in vivo and in silico study.

The aim of this study was to investigate the potential of Ipomoea carnea flower methanolic extract (ICME) as a natural gastroprotective therapy against ethanol-induced gastric ulcers, particularly in individuals exposed to ionizing radiation (IR). The study focused on the Nrf2/HO-1 signaling pathway, which plays a crucial role in protecting the gastrointestinal mucosa from oxidative stress and inflammation. Male Wistar rats were divided into nine groups, the control group received distilled water orally for one week, while other groups were treated with ethanol to induce stomach ulcers, IR exposure, omeprazole, and different doses of ICME in combination with ethanol and/or IR. The study conducted comprehensive analyses, including LC-HRESI-MS/MS, to characterize the phenolic contents of ICME. Additionally, the Nrf2/HO-1 pathway, oxidative stress parameters, gastric pH, and histopathological changes were examined. The results showed that rats treated with IR and/or ethanol exhibited histopathological alterations, increased lipid peroxidation, decreased antioxidant enzyme activity, and reduced expression levels of Nrf2 and HO-1. However, pretreatment with ICME significantly improved these parameters. Phytochemical analysis identified 39 compounds in ICME, with flavonoids, hydroxybenzoic acids, and fatty acids as the predominant compounds. Virtual screening and molecular dynamics simulations suggested that ICME may protect against gastric ulceration by inhibiting oxidative stress and inflammatory mediators. In conclusion, this study demonstrates the potential of ICME as a natural gastroprotective therapy for preventing gastric ulcers. These findings contribute to the development of novel interventions for gastrointestinal disorders using natural plant extracts particularly in individuals with a history of radiation exposure.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Pylorus ligation-induced hyperacidity: synergistic prophylactic effects of linagliptin and L-arginine via up-regulation of EP4 receptor subtype and improvement of vascular endothelial damage.

Gastric hyperacidity and ulceration are chronic diseases characterized by repeated healing followed by re-exacerbation. The study aims to protect against gastric hyperacidity without interfering with gastric acid secretion. Pylorus ligation-induced hyperacidity is commonly utilized in the induction of gastric ulcers.Forty-two rats were distributed into seven groups (n = 6). Group I comprised sham-operated group. Group II served as pylorus-ligation group. Groups III-VII were given oral Linagliptin (LN; 3 and 6 mg/kg), L-arginine (LA; 150 and 300 mg/kg) and their combination (LN 3 + LA 150 mg/kg), respectively for 7 days. On the 8th day, groups II-VII were subjected to pylorus-ligation.Treatment of pylorus-ligated rats with LN, LA and their combination improved the gastric hyperacidity as exhibited by a marked reduction in the gastric juice volume, total and free acidities and pepsin contents with a noticeable increase in pH. Pre-treatment with LN, LA and their combination showed a marked alleviation in the gastric inflammatory indicators evidenced by reduction in the gastric levels of MCP-1and Il-1ß as well as elevation of eNOS levels versus the sham-operated group. A marked up-regulation in the gastric gene expression of PGE, EP4 and VEGF accompanied by an improvement of the histopathologic pictures/scores, and TNF-α and caspase-3 immuno-staining were also recorded.By estimating the combination-index, it can be concluded that combining LN with LA exhibited prophylactic synergistic effects in ameliorating pylorus ligated-induced hyperacidity, mainly via up-regulation of EP4 receptor and improvement of vascular endothelial damage through VEGF expression in gastric mucosa.

[Peptic ulcer of the stomach and duodenum in geriatrics - one disease or two?]

The authors discuss the peculiarities of the terminology of gastric and duodenal ulcers. A clinical, endoscopic and morphological study (determination of the relative area and density of sex hormone receptors in the mucous membrane of the antrum of the stomach) of 760 patients of different ages and genders was carried out. It was found that six clinical parameters (duration of anamnesis, frequency of occurrence of concomitant pathology, epigastric discomfort, belching, heartburn, hereditary predisposition) and two morphological parameters (optical density of estrogen and progesterone receptors) statistically significantly differed in men and women over 60 years old suffering from duodenal ulcer, not gastric localization. The results obtained are consistent with the data of the medical literature, according to which, sexual differences in the pathogenesis of ulceration are more characteristic of ulcers of duodenal localization. Considering that sex differences in the pathogenesis of duodenal ulcers, unlike gastric ulcers, persist until old age, the authors call for a separate study of stomach ulcers and duodenal ulcers, which will probably lead to the need not to combine them two different diseases.

A new protective gel to facilitate ulcer healing in artificial ulcers following oesophageal endoscopic submucosal dissection: a multicentre, randomized trial.

There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report.

BACKGROUND: The coinfection between cytomegalovirus (CMV) and either human herpesvirus-6 (HHV-6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV-8 coinfection after renal transplantation. CASE PRESENTATION: A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi's sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. CONCLUSIONS: We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Treatment with vonoprazan for 3 weeks is not inferior to 8 weeks for the management of gastric ESD: a multicenter noninferiority randomized study.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing. METHODS: This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20-85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD. RESULTS: From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was - 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD. CONCLUSION: This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing. Trial registry number. UMIN000031564.

Vonoprazan vs. Lansoprazole for the treatment of endoscopic submucosal dissection induced gastric ulcer: a systematic review and meta-analysis.

BACKGROUND: Vonoprazan is a potassium competitive acid blocker (P-CAB) approved in Japan in 2014 to treat endoscopic submucosal dissection (ESD)-induced ulcers and bleeding or perforation. Therefore, this meta-analysis aimed to determine whether Vonoprazan is more effective than Lansoprazole in the treatment of ESD-induced ulcers which include ulcer healing and shrinking rate, among others. METHODS: Randomized controlled trials (RCT) and retrospective studies were collected from the PubMed (Medline), Embase, Web of science and Cochrane Library databases. Meanwhile, studies were selected according to predetermined qualification criteria and data were extracted by two researchers. The quality of the methods for published papers was evaluated using the modified Jadad scale. RESULTS: Five studies were included in this meta-analysis, the ulcer healing rate effect was not significantly higher in the intervention groups than in the control groups at 4 weeks, [OR：1.07 (0.51, 2.22), 95% CI, I2=2%, Z=0.18, P=0.86]. There was no significant difference in the ulcer shrinkage rate at 4 weeks [MD：0.20 (-1.51, 1.92), 95% CI, I2=0%, P=0.82] and 8 weeks [MD: -0.09 (-0.30, 0.12), 95% CI, I2=0%, P=0.39]. CONCLUSION: There was no significant difference between Vonoprazan and Lansoprazole in the ulcers induced by treatment after 4 weeks and 8 weeks of treatment with ESD.

The influence of family support during endoscopic submucosal dissection on patient's anxiety.

Background: Psychological problems may promote peptic ulcers. Ulcer-like wounds can be formed after gastric endoscopic submucosal dissection (ESD). The influence of family support on the healing of gastric ESD-induced ulcers remains largely undetermined. Objective: In the present study, we aimed to assess the Hospital Anxiety and Depression Scale (HADS) scores and the incidence of post-ESD complications in patients with family support in the care process and those in the non-relative group. Materials and methods: A total of 191 patients aged between 30 and 70 years who received gastric ESD were evaluated with the Chinese version of HADS. Differences in depression and anxiety between the two groups were compared using the chi-square test and t-test. Multivariable logistic regression models were used to examine whether anxiety and depression were the risk factors for post-ESD complications. Results: The mean values of HADS-A (4.61 ± 2.89 vs. 5.56 ± 3.07, p = 0.042) and HADS-D (4.14 ± 3.03 vs. 4.97 ± 2.61, p = 0.048) scores were significantly lower in patients with accompanying relatives compared with those in the non-relative group. Besides, through the pre-ESD and post-ESD self-contrast, the scores of anxiety and depression in the relative-group were 0.57 and 0.56, respectively (p < 0.001), while those in the non-relative group were increased by 1.43 and 1.49, respectively (p < 0.001). Multivariable logistic regression analysis revealed that HADS-A, HADS-D scores, and age were significantly correlated with post-ESD abdominal pain (P < 0.05). Conclusions: The occurrence and degree of adverse emotions such as psychological anxiety and depression in patients who received gastric ESD with accompanying relatives during hospitalization may were reduced, and the incidence of gastric post-ESD abdominal pain may was also decreased.

[Morphological substantiation of laparoscopic suturing of stomach ulcer with formation of a covered perforation]. / Morfologicheskoe obosnovanie laparoskopicheskogo sposoba ushivaniya probodnoi yazvy zheludka s formirovaniem prikrytoi perforatsii.

OBJECTIVE: Morphological substantiation of laparoscopic suturing of gastric ulcer with formation of a covered perforation. MATERIAL AND METHODS: To analyze morphological tissue reaction in surgical area, we used 12 Chinchilla rabbits. All animals were divided into 2 groups by 6 animals. The main group enrolled rabbits undergoing suturing of perforated gastric ulcer with formation of a covered perforation by anterior stomach wall. In the control group, gastric perforation was sutured by conventional double-row suture. For histological analysis, 2 animals in each group were withdrawn from the experiment after 7, 14 and 21 days. We excised gastric wall within the area of perforation closure. Morphological data on healing process were compared between both groups. RESULTS. S: Tomach deformation after 7 days was more severe in the main group compared to simple suturing. However, these differences were absent after 21 days. Morphological analysis revealed postoperative transmural necrosis after 7 days. Signs of early epithelialization were more obvious in the main group. After 21 postoperative days, we observed almost completely restored differentiation of stomach wall layers in both groups of animals.

Applicability, efficacy, and safety of over-the-scope clips in children.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) are now becoming popular in endoscopy performed in adults for indications such as acute nonvariceal GI bleeding, anastomotic bleeding, and for closure of gastrocutaneous and postgastrostomy fistulae. Varied sizes of clip are available, but even the smallest, 8.5 to 9.8 mm in diameter with its loading device on the tip of the endoscope, increases device and endoscope intubation diameters up to 14.65 mm. This may present challenges in terms of the size of the patient in whom it might be used. OTSCs appear to be effective and safe in the hands of those who are trained appropriately in endoscopy on adult patients; however, the experience of OTSC application in children is not reported. Here we present results of a service evaluation of this technology at 2 regional/national referral pediatric endoscopy units in the United Kingdom and the United States. METHODS: Two tertiary centers' databases were searched to identify cases in which OTSCs were used. Demographics, presentation, anthropometry, comorbidities, efficacy, adverse events, and postprocedure follow-up were recorded, with identification of resolution or recurrence. RESULTS: OTSC procedures were performed on 24 occasions in 20 patients (11 girls) between February 2018 and February 2021. Patients had a mean age of 12 years (range, 5-17) and a mean weight of 44.42 kg (range, 18.2-70.3). Indications were nonhealing PEG site fistulae (n = 7), acute nonvariceal upper GI bleeding (ANUGIB) from gastric ulcers (5), ANUGIB from duodenal ulcers (3), nonhealing bleeding anastomotic ulcer (3), esophageal mucocutaneous fistula (1), and gastric perforation (1). Technical success was achieved in all but 1 case (95%), and clinical success was achieved in 18 cases (90%). CONCLUSIONS: The OTSC device appears to be effective in children (minimum age 5 years and minimum weight 18 kg) in a limited number of situations including anastomotic ulcer, closure of leaking PEG site, gastric perforation, and bleeding peptic ulcers. The operator should be an experienced endotherapeutic endoscopist with specific OTSC training, and the type and size of the OTSC device should be carefully considered, along with any comorbidities of the patient that may preclude success and/or lead to potential adverse events such as esophageal perforation.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucossal dissection: a randomized, open-label trial.

BACKGROUND: Vonoprazan is more potent and longer acting than traditional proton pump inhibitor. Although vonoprazan is expected to be superior to proton pump inhibitor, its efficacy in the treatment of gastric ulcers following endoscopic submucosal dissection (ESD) is not fully understood. The aim of this study was to evaluate the effectiveness of vonoprazan in artificial ulcer healing following ESD. METHODS: Patients with gastric tumors were randomly assigned to the vonoprazan group (group V) or lansoprazole group (group L) after ESD. Patients received intravenous lansoprazole (30 mg) twice on the day of ESD. Thereafter, patients were treated with vonoprazan (20 mg/day) in group V or lansoprazole (30 mg/day) in group L. Esophagogastroduodenoscopy was performed 4 and 8 weeks after the ESD. RESULTS: A total of 168 patients were analyzed. The 4-week healing rate for artificial ulcer was not significantly higher in group V versus group L (17/85, 20.0% vs. 14/83, 16.9%, respectively). In addition, there were no significant differences between the 4-week shrinkage rates between the two groups. Postoperative bleeding occurred in none of the patients in group V and three in group L. One patient in group V presented delayed perforation 2 days after ESD. CONCLUSIONS: Vonoprazan might not be superior to lansoprazole in the healing of artificial gastric ulcer after ESD. TRIAL REGISTRATION: University hospital Medical Information Network (registration number: UMIN000016642), Registered 27 February 2015, https://www.umin.ac.jp/ctr/index-j.htm.