A Rapid Self-Assembling Peptide Hydrogel for Delivery of TFF3 to Promote Gastric Mucosal Injury Repair.

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable ß-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.

[A Giant Gastric Perforation Occurring in the Normal Mucosa during Endoscopy in a Patient with Advanced Gastric Cancer].

The incidence of giant gastric perforation occurring during upper gastrointestinal endoscopy is exceedingly rare. Gastric perforation can arise from excessive air insufflation and is more prevalent in elderly patients with atrophic gastritis. Although giant gastric mucosal lacerations during diagnostic endoscopy have occasionally been reported, there are few reports of giant gastric perforation. The authors experienced a giant gastric perforation occurring in the normal mucosa during endoscopy in an 81-year-old woman with advanced gastric cancer. The patient had reduced gastric extensibility due to the advanced gastric cancer surrounding the entire lower part of her stomach. During continuous air insufflation, only the upper part of the stomach became overdistended, resulting in mucosal rupture and perforation. In addition, old age and the presence of atrophic gastritis contributed to the increased risk of mucosal rupture. The patient was treated successfully with endoscopic clips. This paper reports this case with a review of the relevant literature.

ANKRD22 is a novel therapeutic target for gastric mucosal injury.

Ankyrin repeat domain 22 (ANKRD22) is a nuclear-encoded mitochondrial membrane protein that is highly expressed in normal gastric mucosal epithelial cells and activated macrophages. As a regulator of mitochondrial Ca2+, ANKRD22 could help repair damaged gastric mucosa by promoting the mobilization of LGR5+ gastric epithelial cells via the upregulation of Wnt/ß-catenin pathway activity in a mouse model. Furthermore, the inhibition of ANKRD22 alleviated the macrophage activation-mediated inflammatory response by reducing the phosphorylation of nuclear factor of activated T cells (NFAT). ANKRD22 plays a significant role in the repair of gastric mucosal damage and may become an ideal novel target for the treatment of gastric mucosal injury. However, there is no systematic introduction to ANKRD22 targeting. Therefore, we wrote this review to elaborate the functional mechanism of ANKRD22 in gastric mucosal injury and to analyze its potential application value in clinical therapy.

Gastric acid-response chitosan/alginate/tilapia collagen peptide composite hydrogel: Protection effects on alcohol-induced gastric mucosal injury.

Long-term excessive alcohol intake can easily lead to gastritis, gastric ulcer, and gastric bleeding. In this paper, the gastric acid-responsive hydrogel of CS-NAC/alginate/tilapia collagen peptide (CS-NAC/ALG/TCP) was developed. Its structure and properties were determined. The alcohol-induced gastric mucosal injury models in mice were established to evaluate the protective effects of CS-NAC/ALG/TCP. The results showed that CS-NAC/ALG/TCP was successfully fabricated, and it showed a sustained release of TCP, strong mucoadhesion, and excellent biodegradability in vitro. In the animal experiments, CS-NAC/ALG/TCP improved the oxidative stress status of the gastric mucosa by increasing the levels of SOD, GSH, and CAT in tissues. It also down-regulated the expression of MPO, TNF-α, IL-1ß, and IL-6, and increased the production of gastric protective factors such as PGE2 and NO in mouse stomach, thereby reducing the alcohol-induced inflammation and protecting the gastric mucosal injury. Besides, CS-NAC/ALG/TCP can also increase the activities of alcohol metabolism enzymes to improve alcohol metabolism, thereby reducing alcoholic damage. In conclusion, CS-NAC/ALG/TCP is a promising candidate for the treatment of alcohol-induced gastric injury.

Amelioration of alcohol­induced gastric mucosa damage by oral administration of food­polydeoxyribonucleotides.

Gastritis refers to inflammation caused by injury to the gastric epithelium, which is usually due to excessive alcohol consumption and prolonged use of nonsteroidal anti­inflammatory drugs. Millions of individuals worldwide suffer from this disease. However, the lack of safe and promising treatments makes it urgent to explore and develop leads from natural resources. Therefore, food as medicine may be the best approach for the treatment of these disorders. The present study described the protective effects of food­polydeoxyribonucleotides (f­PDRNs) in a rat model of gastric mucosal injury induced by HCl­EtOH. Administration of f­PDRN was performed with low­PRF002 (26 mg/kg/day), medium­PRF002 (52 mg/kg/day) and high­PRF002 (78 mg/kg/day) on the day of autopsy. The site of damage to the mucous membrane was also analysed. In addition, an increase in gastric juice pH, total acidity of gastric juice and decrease in gastric juice secretion were confirmed, and gastric juice secretion­related factors corresponding to the administration of f­PDRN were analysed. Administration of f­PDRN reduced the mRNA expression of histamine H2 receptor, muscarinic acetylcholine receptor M3, cholecystokinin 2 receptor and H+/K+ ATPase related to gastric acid secretion and downregulation of histamine, myeloperoxidase and cyclic adenosine monophosphate. In addition, it was histologically confirmed that the loss of epithelial cells and the distortion of the mucosa were recovered in the group in which f­PDRN was administered compared to the model group with gastric mucosa damage. In summary, the present study suggested that f­PDRN has therapeutic potential and may have beneficial effects if taken regularly as a food supplement.

ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase.

Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.

Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice.

The transient receptor potential vanilloid channel 4 (TRPV4) is associated with the development of several pathologies, particularly gastric disorders. However, there are no studies associating this receptor with the pathophysiology of gastric erosions. The aim of this study was to investigate the role of TRPV4 in the development of ethanol-induced gastric damage in vivo. Gastric lesions were induced by ethanol in Swiss mice pretreated with TRPV4 antagonists, GSK2193874 (0.1; 0.3 and 0.9 mg/kg) or Ruthenium red (0.03; 0.1 or 0.3 mg/kg) or its agonist, GSK1016790A (0.9 mg/kg). Gastric mucosal samples were taken for histopathology, immunohistochemistry, atomic force microscopy and evaluation of antioxidant parameters. The gastric mucus content and TRPV4 mRNA expression were analyzed. Ethanol exposure induced upregulation of gastric mRNA and protein expression of TRPV4. TRPV4 blockade promoted gastroprotection against ethanol-induced injury on macro- and microscopic levels, leading to reduced hemorrhage, cell loss and edema and enhanced gastric mucosal integrity. Moreover, an increase in superoxide dismutase (SOD) and glutathione (GSH) activity was observed, followed by a decrease in malondialdehyde (MDA) levels. TRPV4 blockade during alcohol challenge reestablished gastric mucus content. The combination of TRPV4 agonist and ethanol revealed macroscopic exacerbation of gastric damage area. Our results confirmed the association of TRPV4 with the development of gastric injury, showing the importance of this receptor for further investigations in the field of gastrointestinal pathophysiology and pharmacology.

Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model.

The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1 ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-κß) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) genes in gastric tissues was determined by real-time PCR; and TNF-α, IL-10, and IL-1ß levels were determined. RJ was found to inhibit iNOS and Nf-κß activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-α and IL-1ß levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.

C-phycocyanin protects against ethanol-induced gastric ulcers in rats: Role of HMGB1/NLRP3/NF-κB pathway.

Gastric ulcer is a widespread inflammatory disease with high socio-economic burden. C-phycocyanin is one of the active constituents of Spirulina microalgae, and although it is well known for its antioxidant and anti-inflammatory properties, its protective effects against gastric ulcer have not yet been identified. High-mobility group box 1 (HMGB1) is a nuclear protein that, once secreted extracellularly, initiates several inflammatory reactions, and it is involved in the pathogenesis of gastric ulcer. The aim of the present study was to investigate the anti-inflammatory and anti-ulcerogenic effects of C-phycocyanin against ethanol-induced gastric ulcer targeting HMGB1/NLRP3/NF-κB pathway. Ulcer induction showed increase in HMGB1 expression through activation of nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome and nuclear factor kappa p65 (NF-κB p65). Moreover, oxidative stress and inflammatory markers were elevated in the ulcer-treated group compared to the normal control group. However, pre-treatment with C-phycocyanin significantly reduced HMGB1 expression via suppression of NLRP3/NF-κB, oxidative markers, IL-1ß, tumour necrosis factor-α (TNF-α) and ulcer index value. These results were consistent with histopathological and immunohistochemistry examination. Thus, C-phycocyanin is a potential therapeutic strategy with anti-inflammatory and anti-ulcerogenic effects against ethanol-induced gastric ulcer.

Antioxidant activity and absorption of cyanidin-3-O-glucoside liposomes in GES-1 cells in vitro.

The use of anthocyanins are limited by their chemical properties. Recent evidence suggests Cyanidin-3-O-glucoside (C3 G) liposomes via the ethanol injection method exhibit improved stability. In the current study, the characterization and cell absorption of C3 G liposomes were explored via transmission electron microscopy and flow cytometry. The internalization of the C3 G liposomes across the gastric epithelial cell monolayer (GES-1 cells) were investigated. Results showed that the particle size and encapsulation efficiency were 234 ± 9.35 nm and 75.0% ± 0.001, respectively. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content were used to evaluate the antioxidant activity of C3 G liposomes. The C3 G liposomes can obviously increased T-AOC and decreased the MDA content.Collectively, C3 G liposomes protected human GES-1 cells from gastric mucosal injury induced by H2O2 by activating the related antioxidant pathway. Our research could provide a new effective treatment strategy for the absorption of stomach drugs.Abbreviations: C3G: Cyanidin-3-O-glucoside; LP: Liposome; GES-1 cells: Human gastric epithelial cell lines; FBS: Fetal Bovine Serum; PBS: Phosphate-buffered saline; PC: Phosphatidylcholine; CH: Cholesterol; MDA: Malondialdehyde; TEM: Transmission electron microscope; FCM: Flow cytometry; FITC: Fluorescein isothiocyanate; DAPI: 4', 6-diamidino-2phenylidole; FT-IR: Fourier Transform infrared spectroscopy; PFA: Paraformaldehyde.

Anti-ulcerogenic activity of Gum Arabic in gastric mucosal injury induced by ethanol in male albino rats.

The present study was performed to evaluate the anti-ulcerogenic activity of Acacia senegal (Gum Arabic) against ethanol-induced gastric mucosal injury in rats. Thirty-six adult male albino rats were divided into 4 groups: group 1 served as a control; group 2 consisted of rats that received 15% of gum in drinking water for 2 weeks; group 3 comprised ulcerated animals administered 5 mL of ethanol/kg body weight by gavage; and group 4 consisted of rats received 15% of gum in drinking water for 2 weeks before ethanol administration. Superoxide dismutase (SOD) glutathione peroxidase (GPx), malondialdehyde (MDA), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin (IL)-B1), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, and albumin were assayed in addition to histological study. The results revealed that ethanol decreased SOD, GPx, and PGE2 in tissue and serum total protein and albumin, while increased MDA in tissue, serum TNF-α, IL-B1, PGE2, ALT, AST, and ALP. Histological findings showed less edema and leucocytes infiltration compared with ulcer group. Furthermore, gum administration elevated PGE2, SOD, and GPx and significantly reduced MDA, TNF-α, and IL-B2. In conclusion, Gum Arabic can enhance gastric protection and sustain the integrity of the gastric mucosa. Novelty The selected dose of Gum Arabic has the ability to decrease the pro-inflammatory cytokines in plasma and gastric tissue, thus enhancing gastric protection and maintaining the integrity of the gastric mucosa. Gum Arabic can compensate for the loss of antioxidants.

Successful treatment of gastric necrosis after ingestion of hydrochloric acid: a two-stage minimally invasive surgical procedure.

Caustic ingestion may cause devastating injuries of the upper gastrointestinal tract and the respiratory system. We report here the successful treatment of a 37-year-old patient who ingested hydrochloric acid (100 mL; 24%) in suicidal intention. An oesophagogastroduodenoscopy revealed extensive necrosis of the gastric mucosa. A diagnostic laparoscopy was performed and confirmed the suspected transmural necrosis which resulted in a discontinuous laparoscopic gastrectomy. During the next days, the oesophageal stump was monitored through frequent oesophagoscopies and showed a good recovery. Thus, it was possible to restore continuity as early as by the sixth postoperative day performing a roux-en-y oesophagojejunostomy using the da Vinci Xi surgical robot. The patient underwent all procedures without any surgical complications and was discharged almost 1 month after initial presentation in good general condition.

[HpaA promotes gastric mucosa injury via stimulating IL-21 secretion of T cells].

Objective To demonstrate HpaA can intensify the inflammatory response and gastric mucosa injury by IL-21 from induced T cell. Methods Biopsy specimens were taken from gastric mucosa of 56 patients with H.pylori infection before and after H.pylori radical elimination by endoscope. The levels of IL-21, matrix metalloproteinase-2 (MMP2) and MMP9 from the biopsy were detected by reverse transcription PCR and Western blot analysis. Meanwhile, the recombinant HpaA was cloned, expressed and purified to stimulate the magnetic cell sorting CD3+ T cells from healthy donors' peripheral blood mononuclear cells (PBMCs), and the level of IL-21 in the supernatant fluid was detected by ELISA. Thereafter, AGS cells were cultured and Western blot analysis was performed to detect the levels of MMP2 and MMP9 in the AGS cells with human IL-21 and anti-IL-21 antibody treatment for 24 hours. Results The protein levels of IL-21 and MMP2 and MMP9 in gastric mucosa infected with H. pylori was significantly higher than that in gastric mucosa after radical treatment of H. pylori. Meanwhile, the recombinant HpaA promoted IL-21 secretion by induced CD3+T cells in vitro. IL-21 stimulated the expression of MMP2 and MMP9 in AGS cells. When IL-21 was blocked by the antibody, the levels of MMP2 and MMP9 in AGS cells decreased significantly. Conclusion HpaA plays a significant role in the gastric mucosa injury caused by H.pylori infection through IL-21 from induced T cells.

Management of early PEG tube dislodgement: simultaneous endoscopic closure of gastric wall defect and PEG replacement.

A 53-year-old man with dysphagia underwent uneventful placement of a percutaneous endoscopic gastrostomy (PEG) tube for long-term enteral feeding access. 11 hours after the procedure, it was discovered that he had accidentally dislodged the feeding tube. On physical examination, he was found to have a benign abdomen without evidence of peritonitis or sepsis. He was observed overnight with serial abdominal examinations and nasogastric decompression. In the morning, he was taken back to the endoscopy suite where endoscopic clips were employed to close the gastric wall defect and a PEG tube was replaced at an adjacent site. The patient was fed 24 hours thereafter and discharged from the hospital 48 hours after the procedure. Early accidental removal of a PEG tube in patients without sepsis or peritonitis can be safely treated with simultaneous endoscopic closure of the gastrotomy and PEG tube replacement, resulting in earlier enteral feeding and shorter hospital stay.

The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats.

The aim of this study is an investigation the protective effects of vitamin C (Vit C), vitamin E (Vit E), ß-carotene, sodium selenate combination in indomethacin-induced gastric mucosal damage in rats. Rats were divided into 6 groups. Group I: Intact animals (control). Group II: Control animals receiving Vit C (100 mg/kg/day), Vit E (100 mg/kg/day), ß-carotene (15 mg/kg/day) and sodium selenate (0.2 mg/kg/day) for 3 days. Group III: Animals receiving 25 mg/kg indomethacin. Group IV: Animals receiving Vit C, Vit E, ß-carotene and sodium selenate (in same doses) for 3 days 2 h before the administration of indomethacin. Group V: Animals receiving ranitidine (150 mg/kg) for 3 days. Group VI: Animals receiving ranitidine for 3 days 2 h before to the administration of indomethacin (in same dose and time). The administration of indomethacin caused a decrease in the levels of glutathione, mucus, hexosamine and in the activities of glutathione-S-transferase, sodium-potassium ATPase, thromboplastic activity and an increase in the aspartate and alanine amino transferase, alkaline phosphatase, catalase, lactate dehydrogenase, myeloperoxidase activities and sialic acid, lipid peroxidation and protein carbonyl levels.  Stomach caspase-8 immun+ cell numbers showed a slight increase while caspase-9 immun+ cell numbers reduced in indomethacin given group compared to control animals. Our results findings suggest that the combination of Vit C, Vit E, ß-carotene, sodium selenate and ranitidine has a protective effect on indomethacin-induced gastric mucosal injury of rats.

Lanthanum phosphate binder-induced iron deficiency anaemia.

Lanthanum carbonate is a phosphate binder that is used to reduce serum phosphate levels in patients with end-stage renal disease (ESRD). Lanthanum forms insoluble lanthanum phosphate complexes that are supposed to pass through the gastrointestinal (GI) tract unabsorbed. Phosphate binders have been reported to deposit in the GI tract and can cause mucosal injury. There are few case reports of GI bleeding associated with phosphate binder deposits. This case report presents a patient with iron deficiency anaemia secondary to biopsy-proven lanthanum deposits in the upper GI tract. There were no overt signs of active GI bleeding. Patient's anaemia improved with discontinuation of the phosphate binder. Lanthanum could be a hidden cause of resistant anaemia among patients with ESRD through asymptomatic GI blood loss.