4-Hydroxynonenal in Redox Homeostasis of Gastrointestinal Mucosa: Implications for the Stomach in Health and Diseases

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense, and activity of detoxifying systems within the cells, as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular, second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling, but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE, and its protein adducts, in response to stressors during acute and chronic gastric injury, are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM, still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques, such as HNE determination by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), as well as modern mass-spectroscopy methods

A marked decrease in heart rate variability in Marfan syndrome patients with confirmed FBN1 mutations

Background: The studies on heart rate variability (HRV), a key predictor of all-cause mortality, in Marfan syndrome (MS), up to now have not been reported, especially in patients with FBN1 mutations. Methods: Among 18 MS patients with the phenotype of MS meeting inclusion criteria 15 have had a FBN1 gene mutation. Short electrocardiography records were taken in the supine position and during orthostatic tests. The control group consisted of 30 apparently healthy nonathletes matched by age and gender. Results: Heart rates in MS patients with the FBN1 mutation were increased in both the supine position and orthostatic test (p < 0.001). Most of the time-domain (standard deviation, pNN50) and frequency-domain (total power, very low, low, and high frequency) parameters of HRV were significantly reduced in the MS patients (p < 0.001). Conclusions: A marked decrease in HRV, documented in the study, may be an important clinical feature in MS patients with confirmed FBN1 gene mutations.

Persistent accumulation of 4-hydroxynonenal-protein adducts in gastric mucosa after Helicobacter pylori eradication [Povećano nakupljanje 4-hidroksinonenal-proteinskih konjugata u želučanoj sluznici zaostaje nakon izlječenja Helicobacter pylori]

Recent studies indicate that oxidative stress caused by Helicobacter pylori and insufficient host antioxidant defense could play important role in pathogenesis of gastrointestinal ulcerations. By specific monoclonal antibodies we have detected weak presence of the major lipid peroxidation bioactive marker 4-hydroxynonenal (HNE) in healthy human gastric mucosa, which strongly increased in case of H. pylori-associated peptic ulcer. Considering physiological presence of HNE on one hand, and high prevalence of H. pylori associated disorders on the other, evaluation of oxidative stress after treatment is important. Therefore, in current study immunohistochemical accumulation and distribution of HNE-protein adducts in gastric mucosa was evaluated with 21 patients having H. pylori-associated duodenal peptic ulcer (DPU) before and one month after eradication of H. pylori. Although dramatic decrease in histological manifestations of inflammation was demonstrated after eradication of H. pylori, initially high immunopositivity for the HNE-protein adducts remained elevated in antrum and even increased in stomach corpus. The observed accumulation and redistribution to higher grades of HNE-immunopositivity in nuclei of glandular cells in gastric corpus indicate augmentation of oxidative stress after treatment and open possibilities for adjuvant antioxidant treatments to protect gastric mucosa from progressive oxidative stress after eradication of H. pylori infection

Synthesis, Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-<i>b</i>][1,2,4]triazole-6(5<i>H</i>)-ones as Possible Anticancer Agents

The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 μM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds

A study of the role of oxidative stress and low-grade inflammation in development of Helicobacter pylori-induced insulin resistance in asymptomatic sedentary young men

A study of the role of oxidative stress and low-grade inflammation in development of [i]Helicobacter[/i] pylori-induced insulin resistance in asymptomatic sedentary young men. OCC World Congress / Annual SFRR-E Conferenc

Helicobacter pylori in sedentary men is linked to higher heart rate, sympathetic activity, and insulin resistance but not inflammation or oxidative stress

Aim To compare anthropometric parameters, body composition, hormonal and inflammatory profiles, oxidative stress indices, and heart rate variability (HRV) in Heliobacter pylori (H.pylori) positive and negative healthy sedentary participants. Methods Among 30 recruited apparently healthy male participants (age between 20 and 40) enrolled in this cross-sectional study, 18 were H.pylori negative and 12 were positive (stool antigen test). Participants underwent routine physical examination and body composition determination. The following biochemical parameters were determined in blood: fasting whole blood glucose, glycated hemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, tumor necrosis factor-alpha, and the urinary level of 1,4-dihydroxynonane mercapturic acid. For HRV evaluation, electrocardiogram in supine position and in orthostatic test was performed. Results H.pylori contamination was not significantly associated with any changes in anthropometric parameters, body composition, blood pressure, fasting glucose, or glycated hemoglobin levels. No significant difference was found for inflammatory markers as well as 1,4-dihydroxynonane mercapturic acid. H.pylori-positive participants, however, had significantly higher heart rate (P=0.009), sympathetic/parasympathetic balance in orthostatic test (P=0.029), fasting insulin level (P=0.037), and HOMA-index (P=0.047). Conclusions H.pylori contamination is linked to a significantly higher heart rate, sympathetic activation, and increased insulin resistance, while inflammatory and oxidative stress markers remain unaffected in healthy sedentary male subjects