American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · May 2021
Heartburn sensation in nonerosive reflux disease: pattern of superficial sensory nerves expressing TRPV1 and epithelial cells expressing ASIC3 receptors.
The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. ⋯ Superficial localization of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 coexpression on epithelial cells in NERD and ERD, suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in patients with NERD, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option. NEW & NOTEWORTHY We demonstrate for the first time that increased pain perception in patients with nonerosive reflux disease likely results from expression of acid-sensitive channels on superficial mucosal afferents and esophageal epithelial cells, raising the potential for topical therapy.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Sep 2020
microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3.
Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In this context, we, thus, aimed to explore the mechanism of miR-382 in epithelial mesenchymal transition (EMT) and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. Gene expression data sets GSE16515, GSE71989, and GSE32676 were screened out, with the findings showing the significance of miR-382 and annexin A3 (Anxa3) in PC. ⋯ Thus, this study provides promising therapeutic targets for PC treatment. NEW & NOTEWORTHY This study focused on the mechanism of miR-382 in epithelial mesenchymal transition and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. We found the inhibitory role of miR-382 in PC in vitro and in vivo.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Aug 2020
ReviewThe mechanism and treatment of gastrointestinal symptoms in patients with COVID-19.
In addition to the typical respiratory response, new coronavirus disease 2019 (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS). If not treated in time, coma and circulatory failure may ensue. ⋯ Indeed, after cells in the lungs become infected by SARS-CoV-2, effector CD4+ T cells reach the small intestine through the gut-lung axis, causing intestinal immune damage and diarrhea; early extensive use of antibacterial and antiviral drugs can also lead to diarrhea in patients. Thus, treatment options for COVID-19 patients should be promptly adjusted when they have gastrointestinal symptoms. As SARS-CoV-2 has been detected in the feces of COVID-19 patients, future prevention and control efforts must consider the possibility of fecal-oral transmission of the virus.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Aug 2020
Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids.
Antibiotic treatment is a standard therapy for Clostridioides difficile infection, but dysbiosis of the gut microbiota due to antibiotic exposure is also a major risk factor for the disease. Following an initial episode of C. difficile infection, a relentless cycle of recurrence can occur, where persistent treatment-related dysbiosis predisposes the patient to subsequent relapse. This study uses a longitudinal study design to compare the effects of a narrow-spectrum (ridinilazole) or broad-spectrum antibiotic (vancomycin) on intestinal bile acid profiles and their associations with gut bacteria over the course of C. difficile infection treatment. ⋯ These results indicate that a narrow-spectrum antibiotic maintains an intestinal bile acid profile associated with a lowered risk of recurrence. NEW & NOTEWORTHY This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent's favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment.
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Am. J. Physiol. Gastrointest. Liver Physiol. · May 2020
Gut leakage enhances sepsis susceptibility in iron-overloaded β-thalassemia mice through macrophage hyperinflammatory responses.
Iron overload induces intestinal-permeability defect (gut leakage), and gut translocation of organismal molecules might enhance systemic inflammation and sepsis severity in patients with thalassemia (Thal). Hence, iron administration in Hbbth3/+ mice, heterozygous β-globin-deficient Thal mice, was explored. Oral iron administration induced more severe secondary hemochromatosis and gut leakage in Thal mice compared with wild-type (WT) mice. ⋯ Preexisting hyperinflammatory cytokines in iron-overloaded Thal enhanced susceptibility toward infection. NEW & NOTEWORTHY Although the impact of iron accumulation in several organs of patients with thalassemia is well known, the adverse effect of iron accumulation in gut is not frequently mentioned. Here, we demonstrated iron-induced gut-permeability defect, impact of organismal molecules from gut translocation of, and macrophage functional defect upon the increased sepsis susceptibility in thalassemia mice.