Critical role of an endogenous gastric peroxidase in controlling oxidative damage in H. pylori-mediated and nonmediated gastric ulcer

Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

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Colonization and Inflammation Deficiencies in Mongolian Gerbils Infected by Helicobacter pylori Chemotaxis Mutants

Infection and Immunity ◽

10.1128/iai.73.3.1820-1827.2005 ◽

2005 ◽

Vol 73 (3) ◽

pp. 1820-1827 ◽

Cited By ~ 78

Author(s):

David J. McGee ◽

Melanie L. Langford ◽

Emily L. Watson ◽

J. Elliot Carter ◽

Yu-Ting Chen ◽

...

Keyword(s):

Helicobacter Pylori ◽

Immune Cell ◽

Response Regulator ◽

Critical Role ◽

Mongolian Gerbils ◽

Wild Type ◽

In The Wild ◽

H Pylori

ABSTRACT Helicobacter pylori causes disease in the human stomach and in mouse and gerbil stomach models. Previous results have shown that motility is critical for H. pylori to colonize mice, gerbils, and other animal models. The role of chemotaxis, however, in colonization and disease is less well understood. Two genes in the H. pylori chemotaxis pathway, cheY and tlpB, which encode the chemotaxis response regulator and a methyl-accepting chemoreceptor, respectively, were disrupted. The cheY mutation was complemented with a wild-type copy of cheY inserted into the chromosomal rdxA gene. The cheY mutant lost chemotaxis but retained motility, while all other strains were motile and chemotactic in vitro. These strains were inoculated into gerbils either alone or in combination with the wild-type strain, and colonization and inflammation were assessed. While the cheY mutant completely failed to colonize gerbil stomachs, the tlpB mutant colonized at levels similar to those of the wild type. With the tlpB mutant, there was a substantial decrease in inflammation in the gerbil stomach compared to that with the wild type. Furthermore, there were differences in the numbers of each immune cell in the tlpB-mutant-infected stomach: the ratio of lymphocytes to neutrophils was about 8 to 1 in the wild type but only about 1 to 1 in the mutant. These results suggest that the TlpB chemoreceptor plays an important role in the inflammatory response while the CheY chemotaxis regulator plays a critical role in initial colonization. Chemotaxis mutants may provide new insights into the steps involved in H. pylori pathogenesis.

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Age and Dietary Vitamin C Intake Affect Brain Physiology in Genetically Modified Mice Expressing Human Lipoprotein(A) and Unable to Synthesize Vitamin C

Current Aging Science ◽

10.2174/1874609814666210706170326 ◽

2021 ◽

Vol 14 ◽

Author(s):

Lei Shi ◽

Aleksandra Niedzwiecki ◽

Matthias Rath

Keyword(s):

Vitamin C ◽

Oxidative Damage ◽

Critical Role ◽

Cholesterol Homeostasis ◽

Dietary Vitamin ◽

Brain Health ◽

Lipoprotein A ◽

Vitamin C Deficiency ◽

The Brain

Aims: Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a “repair factor” in vascular walls weakened by vitamin C deficiency. Background: Humans depend on dietary vitamin C as an important antioxidant, and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, due to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases. Objective: Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human Lipoprotein(a). Method: This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and Lipoprotein(a) deposition in the brain. Result: The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain Lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix. Conclusion: Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Other: Our findings show that optimal vitamin C intake from early life to old age is important in brain health to prevent oxidative stress damage and to maintain cholesterol homeostasis in the brain. More importantly, negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.

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Increased prevalence of precancerous changes in relatives of gastric cancer patients: Critical role of H. pylori

Gastroenterology ◽

10.1016/s0016-5085(00)70410-0 ◽

2000 ◽

Vol 118 (1) ◽

pp. 22-30 ◽

Cited By ~ 202

Author(s):

Emad M. El–Omar ◽

Karin Oien ◽

Lilian S. Murray ◽

Adil El–Nujumi ◽

Angela Wirz ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Critical Role ◽

H Pylori ◽

Gastric Cancer Patients

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Critical Role of NADPH Oxidase in Neuronal Oxidative Damage and Microglia Activation following Traumatic Brain Injury

PLoS ONE ◽

10.1371/journal.pone.0034504 ◽

2012 ◽

Vol 7 (4) ◽

pp. e34504 ◽

Cited By ~ 119

Author(s):

Quan-Guang Zhang ◽

Melissa D. Laird ◽

Dong Han ◽

Khoi Nguyen ◽

Erin Scott ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Oxidative Damage ◽

Nadph Oxidase ◽

Critical Role ◽

Microglia Activation

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Identification of a d-glycero-d-manno-Heptosyltransferase Gene from Helicobacter pylori

Journal of Bacteriology ◽

10.1128/jb.187.15.5156-5165.2005 ◽

2005 ◽

Vol 187 (15) ◽

pp. 5156-5165 ◽

Cited By ~ 32

Author(s):

Koji Hiratsuka ◽

Susan M. Logan ◽

J. Wayne Conlan ◽

Vandana Chandan ◽

Annie Aubry ◽

...

Keyword(s):

Helicobacter Pylori ◽

Critical Role ◽

Outer Core ◽

Core Region ◽

Wild Type ◽

Core Oligosaccharide ◽

Detailed Structural Analysis ◽

Insertional Inactivation ◽

H Pylori

ABSTRACT We have identified a Helicobacter pylori d-glycero-d-manno-heptosyltransferase gene, HP0479, which is involved in the biosynthesis of the outer core region of H. pylori lipopolysaccharide (LPS). Insertional inactivation of HP0479 resulted in formation of a truncated LPS molecule lacking an α-1,6-glucan-, dd-heptose-containing outer core region and O-chain polysaccharide. Detailed structural analysis of purified LPS from HP0479 mutants of strains SS1, 26695, O:3, and PJ1 by a combination of chemical and mass spectrometric methods showed that HP0479 likely encodes α-1,2-d-glycero-d-manno-heptosyltransferase, which adds a d-glycero-d-manno-heptose residue (DDHepII) to a distal dd-heptose of the core oligosaccharide backbone of H. pylori LPS. When the wild-type HP0479 gene was reintegrated into the chromosome of strain 26695 by using an “antibiotic cassette swapping” method, the complete LPS structure was restored. Introduction of the HP0479 mutation into the H. pylori mouse-colonizing Sydney (SS1) strain and the clinical isolate PJ1, which expresses dd-heptoglycan, resulted in the loss of colonization in a mouse model. This indicates that H. pylori expressing a deeply truncated LPS is unable to successfully colonize the murine stomach and provides evidence for a critical role of the outer core region of H. pylori LPS in colonization.

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Survey of Current Practices among Members of CAG in the Follow-Up of Patients Diagnosed with Gastric Ulcer

Canadian Journal of Gastroenterology ◽

10.1155/1999/738907 ◽

1999 ◽

Vol 13 (6) ◽

pp. 489-493 ◽

Cited By ~ 8

Author(s):

Niall P Breslin ◽

Lloyd R Sutherland

Keyword(s):

Gastric Ulcer ◽

Gastric Ulcers ◽

Benign Gastric Ulcer ◽

Canadian Association ◽

Repeat Endoscopy ◽

Risk Of Malignancy ◽

Benign Nature ◽

H Pylori

INTRODUCTION: Guidelines recommend a policy of endoscopic follow-up of all gastric ulcers until healing. Analysis of data from the Alberta Endoscopy Project indicates that fewer than 50% of patients diagnosed with benign gastric ulcer had undergone a repeat procedure. The practice and attitudes of physician members of the Canadian Association of Gastroenterology (CAG) on the follow-up of such patients were assessed.METHODS: A self-administered questionnaire was mailed to members of CAG. Respondents were asked to indicate their practice setting and to estimate the proportion of gastric ulcer patients in whom they perform follow-up endoscopy. They were also asked to indicate factors influencing this choice, including the role ofHelicobacter pylori.RESULTS: Fifty-seven per cent of 220 respondents indicated that they perform repeat endoscopy in 95% to 100% of individuals with benign gastric ulcer. The most common reasons influencing this choice were to ensure healing (86.3%) and to confirm the benign nature of the lesion (79.5%). Nonsteroidal anti-inflammatory drug (NSAID) use (83.2%) and patient ill health (62.9%) were the most common reasons for not repeating the endoscopy. Twenty per cent of individuals indicated thatH pylorihad influenced a change in their practice.DISCUSSION: Physicians vary widely in their follow-up of benign gastric ulcer. Studies on the occurrence of gastric cancer in this setting are not unanimous in their conclusions. Subgroups of patients with NSAID exposure and successfully eradicatedH pyloriinfection may have a lower risk of malignancy. Studies to confirm this are warranted, and modified guidelines may be appropriate.

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Dimethyl fumarate accelerates wound healing under diabetic conditions

Journal of Molecular Endocrinology ◽

10.1530/jme-18-0102 ◽

2018 ◽

Vol 61 (4) ◽

pp. 163-172 ◽

Cited By ~ 4

Author(s):

Ying Li ◽

Fuzhe Ma ◽

Huimin Li ◽

Yuguo Song ◽

Huan Zhang ◽

...

Keyword(s):

Wound Healing ◽

Oxidative Damage ◽

Critical Role ◽

Dimethyl Fumarate ◽

Related Factor ◽

Diabetic Wound ◽

Diabetic Mice ◽

Impaired Wound Healing ◽

Diabetic Wound Healing

Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) – a master of cellular antioxidants scavenging excessive DM-induced free radicals – in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation and accelerated wound closure in diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG) or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) – inducible in DM – in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing.

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