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Background: Saliva has a high nitrite concentration, derived from the enterosalivary recirculation of dietary nitrate, and is the main source of nitrite entering the acidic stomach. Acidification of nitrite in [...]

Background: Bacteria in the oral cavity reduce 25% of the nitrate, absorbed from the diet and secreted into the mouth by the salivary glands to nitrite. Nitrite can be converted [...]

High concentrations of nitric oxide are generated at the gastro-oesophageal (GO) junction due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice containing ascorbic acid. Salivary nitrite is derived from the enterosalivary recirculation of dietary nitrate. Aims: To determine whether nitric oxide generated in the above way will exert nitrosative stress on the adjacent epithelium. Methods: A benchtop model was constructed reproducing the chemistry occurring at the GO junction and incorporating an epithelial compartment maintained at pH 7.4 separated from the lumen by a thin hydrophobic barrier. The secondary amine morpholine was added to each compartment and N-nitrosomorpholine formation at 15 min measured. Results: Adding 100µM nitrite to the acidic (pH 1.5) luminal compartment in the absence of ascorbic acid generated 6.2±2.0 (mean±SE) N-nitrosomorpholine in that compartment and 2.2±0.1 µM in the epithelial compartment. When 100µM nitrite was added to the acidic luminal compartment (pH 1.5) containing ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused into the adjacent epithelial compartment (pH 7.4) where it generated very high concentrations of N-nitrosomorpholine (137±5.6µM). The addition of ascorbic acid or glutathione to the epithelial compartment only reduced this nitric oxide induced nitrosation within the epithelial compartment by 40%. Conclusion: Ascorbic acid in gastric juice prevents acid-catalysed nitrosation within the gastric lumen. However, in doing so it generates nitric oxide which exerts a far higher nitrosative stress on the adjacent epithelium. This mechanism may be relevant to the aetiology of mutagenesis at the GO junction. [ABSTRACT FROM AUTHOR]

Gene flow can have rapid effects on adaptation and is an important evolutionary tool available when undertaking biological conservation and restoration. This tool is underused partly because of the perceived risk of outbreeding depression and loss of mean fitness when different populations are crossed. In this article, we briefly review some theory and empirical findings on how genetic variation is distributed across species ranges, describe known patterns of gene flow in nature with respect to environmental gradients, and highlight the effects of gene flow on adaptation in small or stressed populations in challenging environments (e.g., at species range limits). We then present a case study involving crosses at varying spatial scales among mountain populations of a trigger plant (Stylidium armeria: Stylidiaceae) in the Australian Alps to highlight how some issues around gene flow effects can be evaluated. We found evidence of outbreeding depression in seed production at greater geographic distances. Nevertheless, we found no evidence of maladaptive gene flow effects in likelihood of germination, plant performance (size), and performance variance, suggesting that gene flow at all spatial scales produces offspring with high adaptive potential. This case study demonstrates a path to evaluating how increasing sources of gene flow in managed wild and restored populations could identify some offspring with high fitness that could bolster the ability of populations to adapt to future environmental changes. We suggest further ways in which managers and researchers can act to understand and consider adaptive gene flow in natural and conservation contexts under rapidly changing conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting., Methods: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared., Results: Serum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)]., Conclusion: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear., Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach., Methods: Nested case-control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin., Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1)., Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer.

High luminal concentrations of nitric oxide are generated at the human gastro-oesophaegal junction and within Barrett's oesophagus due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice. Salivary nitrite is derived from the entero-salivary recirculation of dietary nitrate. Our aim was to determine whether nitric oxide generated within the lumen will exert nitrosative stress on the adjacent epithelium. A benchtop model was constructed reproducing the nitrite chemistry occurring within the lumen of the upper gastrointestinal tract where saliva encounters acidic gastric juice. It incorporated an epithelial compartment maintained at pH 7.4 and separated from the lumen by a hydrophobic barrier with the properties of the epithelial lipid cell membrane. The secondary amine morpholine was used to measure N-nitroso compound formation in both the lumen and epithelial compartment. Adding 100 micro M nitrite to the acidic (pH 1.5) luminal compartment depleted of ascorbic acid generated 6.2 +/- 2.0 micro M (mean +/- SE) N-nitrosomorpholine in that compartment and 2.2 +/- 0.1 micro M nitrosomorpholine in the epithelial compartment at 30 min. When 100 micro M nitrite was added to the acidic luminal compartment containing physiological concentrations of ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused from the luminal compartment into the epithelial compartment and there generated very high concentrations of N-nitrosomorpholine (137 +/- 5.6 micro M at 30 min). The addition of ascorbic acid or glutathione to the epithelial compartment could only reduce nitric oxide-induced nitrosation within that compartment by 40%. The nitrate-derived nitric oxide generated within the lumen where saliva encounters gastric acid is likely to exert substantial nitrosative stress on the adjacent epithelium. This may contribute to the high prevalence of mutagenesis at this anatomical site.