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Main antioxidant enzymes and their substrates. These enzymes have altered functions in Crohn’s disease.
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Crohn’s disease (CD) is an inflammatory disorder characterised by a transmural inflammation of the intestinal wall. Although the physiopathology of the disease is not yet fully understood, it is clear that the immune response plays an important role in it. This hyperreactive immune system is accompanied by the presence of unregulated reactive oxyge...
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Background
Inflammatory bowel disease (IBD) is commonly divided into 2 entities: Crohn’s disease (CD) and ulcerative colitis (UC). Differentiating between these entities when dealing with IBD confined to the colon is important, especially when planning surgical treatment. Due to ambiguous histological or endoscopic findings, accurate diagnosis is n...
Citations
... Inflammatory bowel disease (IBD) is a complex and multifactorial relapsing gastrointestinal inflammatory condition with a continuously increasing incidence and can involve the entire gastrointestinal tract [1,2]. Crohn's disease (CD) and ulcerative colitis (UC), the two main types of IBD, affect up to 1% of the population, negatively influencing the quality of life of patients and their relatives [3,4]. ...
... The CASP9 gene rs4645983 polymorphism has been associated with short-term non-response to ADA [42]. Therefore, CASP9 variants could be the underlying factors influencing the imbalanced apoptosis in peripheral blood lymphocytes in patients with CD [2,3]. ...
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn’s disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual’s drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
... ROS increases gradually with the inflammation production and promotes the inflammation development by expending antioxidant substances. 76 Therefore, L d CaP d NPs and Dsp inhibited the inflammatory factors production by regulating macrophage polarization, thereby reducing the ROS production, and recovering the activity of SOD to improve the antioxidant capacity. Since L d CaP d NPs could comprehensively regulate the macrophage polarization by creating a microenvironment conducive to M2 polarization and directly regulating macrophage polarization, their inhibitory ability on inflammatory factors and oxidative stress was stronger than that of Dsp. ...
Background
The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms.
Purpose
A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects.
Methods
Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model.
Results
The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy.
Conclusion
The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.
... These ROS promote cell damage and harm tissue integrity by preventing the accumulation of antioxidant defenses in host cells. For example, oxidative damage is observed in the intestinal tissues and peripheral blood leukocytes of patients with CD (72). Moreover, CD patients have lower levels of antioxidant vitamins A, C, E, and beta-carotene in their blood and intestinal mucosa, as well as reduced activity of key cellular AOEs such as glutathione peroxidase and SOD (73). ...
Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-kB) and nuclear factor erythroid 2-related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.
... Epigenetics includes chemical modifications to DNA (methylation and demethylation) without changing the underlying DNA sequence; modifications to histone proteins, which are components of the nucleosomes that DNA wraps around; and the action of noncoding RNAs such as microRNAs [12]. Epigenetics is therefore considered a regulator of the complex machinery behind inflammatory disorders, contributing to the expression of inflammation-associated genes [10] and is therefore associated with IBD pathogenesis [7,19,20]. ...
... Due to its complexity, it is an interesting factor that needs to be explored in detail in other specific reviews. On the other hand, noncoding RNAs, especially microRNAs, represent the most studied epigenetic mechanism in IBD, and many reviews have dealt with this topic [6,19]. Therefore, we have focused on describing in detail other more novel and less studied epigenetic mechanisms in IBD. ...
... chemical modifications to DNA (methylation and demethylation) without changin underlying DNA sequence; modifications to histone proteins, which are componen the nucleosomes that DNA wraps around; and the action of noncoding RNAs su microRNAs [12]. Epigenetics is therefore considered a regulator of the complex mach behind inflammatory disorders, contributing to the expression of inflammation-as ated genes [10] and is therefore associated with IBD pathogenesis [7,19,20]. ...
The immune system and environmental factors are involved in various diseases, such as inflammatory bowel disease (IBD), through their effect on genetics, which modulates immune cells. IBD encompasses two main phenotypes, Crohn’s disease, and ulcerative colitis, which are manifested as chronic and systemic relapse-remitting gastrointestinal tract disorders with rising global incidence and prevalence. The pathophysiology of IBD is complex and not fully understood. Epigenetic research has resulted in valuable information for unraveling the etiology of this immune-mediated disease. Thus, the main objective of the present review is to summarize the current findings on the role of epigenetic mechanisms in IBD to shed light on their potential clinical relevance. This review focuses on the latest evidence regarding peripheral blood mononuclear cells and epigenetic changes in histone modification, DNA methylation, and telomere shortening in IBD. The various identified epigenetic DNA profiles with clinical value in IBD could be used as biomarkers for more accurately predicting disease development, treatment response, and therapy-related adverse events. Ultimately, the information presented here could be of potential relevance for future clinical practice in developing more efficient and precise medicine to improve the quality of life for patients with IBD.
... Of note, we found a significant difference in 4 out of the 14 CAT-gene SNPs evaluated (rs7943316, rs475043, rs769217, and rs525938) between the CD patients and the control group (Table 3). Some of these four polymorphisms have been previously implicated with the pathogenesis of inflammatory bowel disease (IBD) [16,18,19]. ...
Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.
... The complex etiology of CD is unclear; nevertheless, numerous features, including the immunological system of the host and genetics, may act a key part in disrupting intestinal homeostasis, resulting in a deregulated inflammatory response of the G.I.T. (58). Several investigations have found an increase in reactive oxygen species and a reduction in antioxidant levels in CD patients' intestinal mucosa and plasma (59). Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are two key intracellular antioxidant enzymes that protect cells from the damaging effects of ROS (60). ...
Background: Saliva is the first defense system of the body
through its antioxidant status (total antioxidant capacity),
which is either enzymatic or non-enzymatic antioxidants,
which block the process of oxidation by neutralizing free
radicals; therefore, the objective of this review is to evaluate
the role of salivary antioxidant biomarkers in the diagnosis
and monitoring of many oral and periodontal diseases and
related systemic disorders. Method: We searched for articles
published on PubMed and Google Scholar in the last 20 years
and then filtered the mints 60 papers according to the
following keywords: saliva, total antioxidant capacity (TAC)
and oxidative stress (OS). Conclusion: Saliva samples can be
beneficial in demonstrating oxidant-antioxidant balance in
oral and systemic illnesses and may be a suitable sample type
in the diagnosis and monitoring of many pathologies in the
body
... MicroRNAs (miRs) are noncoding, single-stranded RNAs that regulate gene expression at the post-transcriptional level [9]. MiRs base-pair with target messenger RNAs (mRNAs) to silence complexes and degrade mRNAs or block translation, thus influencing protein synthesis [10]. ...
Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.
... Кроме перечисленных факторов, одним из механизмов, вовлеченных в развитие ВЗК, является окислительный стресс [8,9,10]. Окислительный стресс при ВЗК способствует повреждению не только слизистой оболочки, но и более глубоких слоев кишечной стенки, развитию ишемии и, таким образом, усугублению воспаления [11]. ...
Aim. To study the level of oxidative stress and the state of antioxidant protection of blood in children with inflammatory bowel diseases before and after a course of hyperbaric oxygenation Materials and methods. Markers of oxidative stress (malondialdehyde of blood plasma and erythrocytes, ischemia-modified blood plasma albumin) and indicators of antioxidant blood defense (catalase and reduced erythrocyte glutathione) were studied in 16 patients with Crohn’s disease and 11 patients with ulcerative colitis aged 6 to 17 years, thiol groups of blood plasma). Similar indicators were studied after a course of hyperbaric oxygenation, carried out in a single-seat air-oxygen pressure chamber “BaroOx 1.0”. The course consisted of 5-8 daily sessions in the 1.3-1.4 ata regimen for 40 minutes. Results. In pediatric patients with Crohn’s disease and ulcerative colitis, a significant development of oxidative stress (an increase in the level of malondialdehyde in blood plasma and erythrocytes, ischemia-modified blood plasma albumin) and changes in antioxidant protection indicators were revealed. After a course of hyperbaric oxygenation, a significant decrease in the concentration of markers of oxidative stress and an increase in the antioxidant defense of the blood were noted. Conclusion. The use of hyperbaric oxygenation in children with inflammatory bowel diseases significantly reduces the manifestations of oxidative stress and intensifies the antioxidant defense of the blood.
... ROS promote cell damage by preventing the accumulation of antioxidant defenses in cells. For example, oxidative damage is observed in CD patients' intestinal mucosa as well as their peripheral blood leukocytes [14]. Immune cells that enter the mucosa produce a number of ROS that can be harmful to tissue integrity. ...
Chronic intestinal disorders (CID) are characterized by persistent, or recurrent gastrointestinal (GI) signs present for at least three weeks. In human medicine, inflammatory bowel disease (IBD) is a group of chronic GI diseases and includes Crohn’s disease (CD) and ulcerative colitis (UC). On the other hand, the general term chronic enteropathies (CE) is preferred in veterinary medicine. Different therapeutic approaches to these diseases are used in both humans and pets. This review is focused on the use of traditional therapies and nutraceuticals with specific antioxidant properties, for the treatment of CID in humans and animal patients. There is strong evidence of the antioxidant properties of the nutraceuticals included in this review, but few studies report their use for treating CID in humans and none in animals. Despite this fact, the majority of the nutraceuticals described in the present article could be considered as promising alternatives for the regular treatment of CID in human and veterinary medicine.
... The complex etiology of CD is unclear; nevertheless, numerous features, including the immunological system of the host and genetics, may act a key part in disrupting intestinal homeostasis, resulting in a deregulated inflammatory response of the G.I.T. (58). Several investigations have found an increase in reactive oxygen species and a reduction in antioxidant levels in CD patients' intestinal mucosa and plasma (59). Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are two key intracellular antioxidant enzymes that protect cells from the damaging effects of ROS (60). ...
Background: Saliva is the first defense system of the body
through its antioxidant status (total antioxidant capacity),
which is either enzymatic or non-enzymatic antioxidants,
which block the process of oxidation by neutralizing free
radicals; therefore, the objective of this review is to evaluate
the role of salivary antioxidant biomarkers in the diagnosis
and monitoring of many oral and periodontal diseases and
related systemic disorders. Method: We searched for articles
published on PubMed and Google Scholar in the last 20 years
and then filtered the mints 60 papers according to the
following keywords: saliva, total antioxidant capacity (TAC)
and oxidative stress (OS). Conclusion: Saliva samples can be
beneficial in demonstrating oxidant-antioxidant balance in
oral and systemic illnesses and may be a suitable sample type
in the diagnosis and monitoring of many pathologies in the
body.
