scholarly journals Retraction of: Involvement of the TLR4/NF-κB Signaling Pathway in the Repair of Esophageal Mucosa Injury in Rats with Gastroesophageal Reflux Disease

2021 ◽  
Vol 55 (5) ◽  
pp. 676-676
2018 ◽  
Vol 51 (4) ◽  
pp. 1645-1657 ◽  
Author(s):  
Hai-Xiang Yu ◽  
Xiao-Long Wang ◽  
Le-Ning Zhang ◽  
Ji Zhang ◽  
Wei Zhao

Background/Aims: Numerous studies have highlighted the activation of NF-κB in the esophageal mucosa during the early stages of gastroesophageal reflux disease (GERD). The present study aimed to investigate the role of the TLR4/NF-κB signaling pathway in GERD rat models. Methods: Wistar rats (n = 60) were recruited to establish a GERD animal model. Distal esophageal pH was assessed, followed by determination of the contents of thiobarbituric acid-reactive species (TBARS) and reactive oxygen species (ROS) in esophageal mucosa homogenate. ELISA was employed to detect the levels of inflammatory factors (IL-6, IL-8, IL-10 and TNF-α) in esophageal mucosa. The expression of MMP-3, MPP-9, Cldn1 and Cldn4 was determined by immunohistochemistry. RT-qPCR and western blot analysis were applied to evaluate the protein expressions in TLR4/NF-κB signaling pathway, while TUNEL staining was utilized to examine the apoptosis rate in the esophageal mucosal tissues. Results: Distal esophageal pH of the rats was higher in the GERD + PDTC group than in other groups. Levels of inflammatory factors in esophageal mucosal tissues were downregulated with the inhibition of NF-κB, which was determined to be associated with the decreased contents of TBARS and ROS. Moreover, decreased MMP-3 and MPP-9 in addition to elevated Cldn1 and Cldn4 were detected in the esophageal mucosa as a result of the inactivation of NF-κB. The TLR4/NF-κB signaling pathway-related proteins (TLR4, NF-κB and IκBα); the rate of apoptosis was demonstrated to be suppressed in the GERD + PDTC group, while inactivating NF-κB was found to alleviate the tissue damage observed in the esophageal mucosa. Conclusion: The key findings of the current study demonstrate that the inactivation of the TLR4/NF-κB signaling pathway alleviates oxidative stress injury and promotes the repair of esophageal mucosal injury among rats with GERD, highlighting a potential novel GERD mechanism.


Peptides ◽  
2009 ◽  
Vol 30 (6) ◽  
pp. 1082-1087 ◽  
Author(s):  
Thomas Wex ◽  
Klaus Mönkemüller ◽  
Doerthe Kuester ◽  
Lucia Fry ◽  
Arne Kandulski ◽  
...  

2021 ◽  
pp. 30-37
Author(s):  
D. N. Andreev ◽  
A. V. Zaborovsky ◽  
E. G. Lobanova

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.


2019 ◽  
Vol 91 (8) ◽  
pp. 4-11 ◽  
Author(s):  
I V Maev ◽  
D N Andreev ◽  
Yu A Kucheryavyy ◽  
R I Shaburov

Gastroesophageal reflux disease (GERD) is characterized by high morbidity and a significant decrease in the quality of life of patients, and is a major risk factor for esophageal adenocarcinoma. Nowadays, antisecretory therapy with proton pump inhibitors (PPI) is the "gold standard" of conservative treatment of GERD, but in some cases this therapy is unsuccessful. According to various studies, the prevalence of refractory GERD can reach 30-40%. The latest scientific data in the field of genetics and pathophysiology of GERD demonstrate that a disruption of the barrier function of the esophageal mucosa and an increase of its permeability can be the leading causes of refractoriness. Thus, the optimal therapy for patients with GERD should not only suppress the secretion of hydrochloric acid, but also restore the barrier function of the mucous membrane, providing an esophagoprotective effect. To achieve these goals, Alfasoxx was developed, which consists of a mixture of low molecular weight hyaluronic acid and low molecular weight chondroitin sulfate dissolved in a bioadhesive carrier (poloxamer 407). The clinical efficacy of this product has been confirmed by three prospective, randomized, placebo - controlled trials. Alfasoxx has a healing and restorative effect towards the esophageal epithelium and due to high ability for bioadhesion provides long - term protection of the mucous membrane of the esophagus. Combination therapy for GERD with the use of PPI and an esophagoprotector offers new perspectives for the treatment of patients with GERD.


2021 ◽  
Vol 17 (4) ◽  
pp. 34-39
Author(s):  
I.V. Matoshina ◽  
◽  
M.M. Fedorin ◽  
M.A. Livzan ◽  
S.I. Mozgovoy

Gastroesophageal reflux disease (GERD) is the most common of all acid-related diseases, it is recognized as the leading cause of esophageal adenocarcinoma. The natural factor of protection against aggressive refluxate components is the integrity of the esophageal mucosa, which performs a barrier function with the participation of a number of mechanical, chemical and immunological mechanisms. Their damage under the regular influence of acidic or mixed reflux causes the development of the pathological process. The review was prepared to systematize knowledge of the main components of mucosal barrier of the esophagus providing resistance of mucosa under conditions of GERD. The literature was searched in Embase, PubMed, and Google Scholar using the keywords: gastroesophageal reflux disease, mucosal protection, esophageal mucosa epithelium, dense contact proteins, epithelial protection, esophagoprotection. The main structural and functional components of esophageal mucosal protection were emphasized


2010 ◽  
Vol 134 (6) ◽  
pp. 815-825
Author(s):  
Muriel Genevay ◽  
Laura Rubbia-Brandt ◽  
Anne-Laure Rougemont

Abstract Context.—Although the healthy esophageal mucosa contains no eosinophils, eosinophilic infiltration is observed in 2 major clinicopathologic settings: gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EE). The prevalence of EE is increasing in many countries, and this increase seems only partly to be due to a better awareness of the pathology, following the relatively recent description of EE. Gastroesophageal reflux disease and EE represent 2 entities that do not respond to the same treatment modalities and, thus, need to be distinguished. However, diagnostic criteria of EE have been defined arbitrarily, and the more recent articles tend to prove that the overlap with GERD is probably greater than initially believed, leading the authors to advise strict exclusion of GERD before considering the diagnosis of EE. Objectives.—To provide pathologists with the currently proposed histologic criteria of GERD and EE, to stress the need to combine these criteria with clinical data and endoscopic findings, and to outline the remaining controversies. Data Sources.—This review is based on selected articles identified by a PubMed (US National Library of Medicine, Bethesda, Maryland) search of the literature in English for GERD and EE, a recent review by the American Gastroenterological Association (Bethesda), the Proceedings of the First International Gastrointestinal Eosinophil Research Symposium, and the authors' experience. Conclusions.—Proper identification of the etiology of eosinophilic infiltration of the esophagus allows accurate medical or surgical treatment and follow-up. Eosinophilic esophagitis and GERD diagnoses require integration of the histologic findings with the clinical and endoscopic data.


Author(s):  
Mirvasit Karimov ◽  
Abdujabar Akhmatkhodjaev

Comparative assessment of clinical efficiency of omeprazole and rabeprazole in treating gastroesophageal reflux disease (GERD). 65 patients with a verified diagnosis GERD were examined. Comparative clinical investigations of using ofomeprazole and rabeprazole have revealed effectiveness of both drugs in the therapy of GERD. However, rabeprazoleshowed antisecretory action in the earlier periods, providing stable clinical remission of GERD and early scarring of erosivelesions of the esophageal mucosa, compared with omeprazole


2014 ◽  
Vol 146 (5) ◽  
pp. S-859
Author(s):  
Arne Kandulski ◽  
Sybille Pohnert ◽  
Dominique Danielewicz ◽  
Jochen Weigt ◽  
Thomas Wex ◽  
...  

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