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Diabetes obesity and metabolism a journal of pharmacology and therapeutics, ‪Margit Solymár‬ - ‪Google Tudós‬

Go to: 5. Therapeutic Benefits of Avenanthramides There is compelling evidence that oxidative stress plays a major role in the pathogenesis and progression of major human diseases, including atherosclerosis, diabetes, inflammatory diseases, cardiovascular diseases, cancer, and neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's AD and Parkinson's PD diseases [ 63 ], and is also implicated in aging [ 64 ]. Oxidative stress occurs either when excess ROS are produced in cells, which could overwhelm the normal antioxidant capacity, or upon impairment of antioxidant defense mechanisms.

ROS toxicity contributes to protein, lipid and DNA damage, inflammation, cell and tissue injury, and apoptosis.

 - Он подал едва заметный знак, и ворота распахнулись. Проехав еще полмили, Сьюзан подверглась той же процедуре перед столь же внушительной оградой, по которой был пропущен электрический ток. «Давайте же, ребята… уже миллион раз вы меня проверяли». Когда она приблизилась к последнему контрольно-пропускному пункту, коренастый часовой с двумя сторожевыми псами на поводке и автоматом посмотрел на номерной знак ее машины и кивком разрешил следовать. Она проехала по Кэнин-роуд еще сотню метров и въехала на стоянку «С», предназначенную для сотрудников.

Nevertheless, ROS also play important physiological functions, whereas emerging evidence demonstrates that the biological impact of ROS depends not only on their intracellular levels and rate of formation and decay but also on their chemical nature and subcellular localization [ 6566 ]. Thus, inappropriate removal of ROS by antioxidants may cause paradoxical reductive stress and thereby induce or promote disease [ 636768 diabetes obesity and metabolism a journal of pharmacology and therapeutics.

Due to their capacity to scavenge ROS and prevent oxidative stress, antioxidants including natural and synthetic phenolic compounds have long been credited with helping to live longer and stay healthier, and looked upon as effective therapeutic options for prevention and treatment of various oxidative stress-related diseases.

Natural antioxidants are primarily phenolics that may occur in all parts of plants [ 69 ].

Specifically, beneficial effects on human health of phenolic compounds with high antioxidant properties obtained from oats have been reported in many studies and shown to protect cells against oxidative damage [ 2370 ]. Furthermore, several compositions containing oat Avns or derivatives have been described in pharmaceutical patents for use in cosmetic, nutraceutical, and therapeutic preparations due to their antioxidant, anti-inflammatory, anti-itching, antiallergic, antihistaminic, antiasthmatic, and antiaging activities.

In particular, the synthetic drug Tranilast has been approved since in Japan and South Korea and, as mentioned above, is currently used as an antihistamine to treat bronchial asthma, atopic dermatitis, allergic conjunctivitis, allergic rhinitis, and other allergic disorders, with indications for keloids and hypertrophic scars, scleroderma, and other skin disease related to excessive fibrosis [ 36 ].

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In addition, it was proposed for treatment of autoimmune diseases, such as arthritis and multiple sclerosis, and as an inhibitor of angiogenesis [ 3771 ]. Moreover, the high potential of Tranilast in inhibiting pathological cellular growth processes, such as tumor-related ones, was investigated with promising results [ 375872 — 81 ].

On the other hand, a randomized, placebo-controlled, double-blind pilot study, vércukor és koleszterin mérő egyben to determine whether the Avn-enriched bran reduces biomarkers diabetes obesity and metabolism a journal of pharmacology and therapeutics inflammation, demonstrated that consuming Avns in a whole food form, that is, Avn-enriched oat bran, may affect specific biomarkers of inflammation in older, overweight, or obese adults [ 82 ].

Bartfai, Tamas

Considering the anti-inflammatory properties of Avns and their capacity to inhibit smooth muscle cell proliferation and increase NO production, these compounds were proposed for prevention or therapy of atherosclerosis and associated cardiovascular diseases.

Data also pointed to the potential benefit of including oats and oat bran in daily meals over the long term [ 26 ]. Interestingly, recent ujjbetegség diabetes kezelés highlighted the combined antioxidant, anti-inflammatory, and anticancer effects of individual synthetized Avns and a mixture of natural Avns on CaCo-2 and Hep3B cancer legjobb édesítőszer cukorbetegeknek, showing that both natural and synthetic Avns activate caspases 2, 8, and 3 and downregulate hTERT, MDR1, and COX-2 genes, and suggesting that oat-based foods fortified with Avns could be an alternative to produce functional foods with major health benefits [ 83 ].

Furthermore and importantly, recent findings demonstrated that both Tranilast and YAvns were effective in rescuing prooxidant and proinflammatory phenotypes associated with CCM disease, a cerebrovascular disorder associated with altered redox homeostasis and signaling and enhanced susceptibility to oxidative stress and inflammatory insults, thus widening the therapeutic potential of these compounds [ 41 ].

Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats

Go to: 6. Avenanthramides as Potential Therapeutics for Cerebral Cavernous Malformation Disease CCM, also known as cavernous angioma or cavernoma, is a major cerebrovascular disease characterized by clusters of abnormally dilated and leaky capillaries occurring in brain, spinal cord, and retina, with a prevalence of 0.

These vascular anomalies, referred to as CCM lesions, can be single or multiple up to hundredsas detected by magnetic resonance imaging, and may result in severe clinical symptoms at any age, including recurrent headaches, focal neurological deficits, seizures, stroke, and intracerebral hemorrhage ICH [ 84 ]. It may arise sporadically or is inherited as autosomal dominant condition with incomplete penetrance and highly variable expressivity even among members of the same family, including wide differences in lesion number, size, and susceptibility to ICH [ 84 — 86 ].

Despite significant recent advances in our understanding of the pathophysiology of CCM disease, no direct therapeutic approaches are available so far, besides the surgical removal of accessible lesions [ 8487 ]. Accumulated evidence demonstrates that loss-of-function mutations of CCM genes have pleiotropic effects on several redox-sensitive molecules and mechanisms that control cellular homeostasis and defenses against oxidative stress and inflammation, thereby sensitizing cells to local oxidative stress and inflammatory events [ 848688 — 95 ].

In particular, KRIT1 loss-of-function has been shown to affect major antioxidant pathways and mechanisms, including the FOXO1-SOD2 axis and the Nrf2 antioxidant pathway [ 8994 ], and the autophagic degradation of dysfunctional, ROS-generating mitochondria [ 8991 ]. On the other hand, there is emerging evidence that Avns, including YAvns, can enhance cellular defenses against oxidative stress by inhibiting the activity of prooxidant and proinflammatory proteins, such as NADPH oxidase and NF-κB [ 41 ], and stimulating the upregulation of antioxidant molecules, such as GSH and SOD2 [ 2140 ].

Furthermore, both YAvns and Tranilast were able to induce a rescue of major phenotypic signatures in a mouse model of CCM disease, including altered redox homeostasis diabetes obesity and metabolism a journal of pharmacology and therapeutics signaling, destabilized endothelial cell-cell junctions and blood-brain barrier, enhanced vascular permeability, and reduced susceptibility to oxidative stress and inflammatory insults, suggesting potential therapeutic benefits for CCM disease [ 41 ].

Copyright © Andrea Kurucz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Alzheimer's disease AD is a neurodegenerative disorder with cognitive impairment.

Further studies aimed at a comprehensive characterization of the pleiotropic effects and mechanisms of action of natural and recombinant Avns will provide useful insights into these and other promising therapeutic benefits. Go to: 7. Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses.

diabetes obesity and metabolism a journal of pharmacology and therapeutics dairy szérum cukorbetegség kezelésének

Today, it is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams, and has been approved as a skin protectant by the US Food and Drug Administration FDA [ 27 ].

Among oat constituents, Avns are known to suppress histamine release at very low doses, helping to plump up the skin, reduce wrinkles, and restore the skin natural barrier. Indeed, oat Avns have been shown to represent the main group of active polyphenolic antioxidants responsible for oatmeal anti-inflammatory, antierythema antirednessantipruritic anti-itchingand antihistaminic properties.

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Consistently, several studies have demonstrated their benefits in reducing eczema and other inflammatory skin conditions [ 16 ]. Another health and antiaging benefit of oat Avns is their antigenotoxic activity, which can protect the DNA of epidermal cells against environmental insults, including UV irradiation [ 21 ]. In hair care, oat Avns have been shown to prevent lipid peroxidation in human hair follicles and alleviate scalp itchiness and tenderness, indicating Avns as an ideal active ingredient for scalp care formulations [ 25 ].

Furthermore, Avns have been shown to prevent oxidation of LDL cholesterol and inhibit the first stages of atherosclerosis, gaining the reputation of being able to protect the aging cardiovascular system. In addition, as also described in this review, several studies in the past few years have suggested that oat Avns may be beneficial in the treatment of various aging-related human diseases associated with chronic oxidative stress and inflammation [ 96 ].

Notably, Avns exert their strong antioxidant and anti-inflammatory properties even at very low doses.

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Taken together, the established beneficial effects of Avns in skin protection and treatment of dermatological diseases, and their emerging potentiality to prevent and treat chronic oxidative stress and inflammation associated with onset, progression and severity of aging-related diseases, including metabolic, cardiovascular, cerebrovascular and neurodegenerative diseases, point to these compounds as promising new elixir of youth with both cosmetic and pharmaceutical applications.

Go to: 8. Foodomics for Elucidating Molecular Pathways Underlying Biological Effects of Avenanthramides in Chronic Diseases Nutrition research has traditionally explored the functional importance of diverse food categories through a careful evaluation of various physiological phenomena and molecular markers characterizing a group of individuals fed with a defined diet.

Hence, not only genetic factors but also homeostatic alterations related to the environment may be crucial in disease onset, progression, and severity.

diabetes obesity and metabolism a journal of pharmacology and therapeutics a cukorbetegség kezelése a hazai

In the last few years, nutrition research has moved from classical physiology and epidemiology to chemical biology, molecular biology, and genetics [ 97 ].

In this context, foodomics has emerged as a novel and multidisciplinary research field in nutrition science, which aims at elucidating how diet can influence organism health []. The study of these complex interactions requires the integration of different analytical approaches generating various dataset, which then are interpreted according to a system biology perspective by dedicated bioinformatic methods [ ].

Integration of all information according to a multiomic elaboration allows simultaneously deciphering gene expression pathways, protein levels, and metabolite concentrations that are affected in healthy individuals experiencing a certain diet; the same information can be obtained for subjects suffering a certain pathological condition.

Thus, it is possible to formulate dietary recommendations based on a system biology perspective to ensure a healthy condition or to prevent and treat chronic diseases, such as CVDs, obesity, and cancer [ ]. Due to the complexity of these studies, their results were often published in different articles.

diabetes obesity and metabolism a journal of pharmacology and therapeutics wolfram szindróma

In the next future, it is desirable that advanced foodomics studies, analogous to those reported above for other foods, will also be performed on organisms or animal models of human diseases fed with oat compounds, including isolated Avns and their recombinant derivatives, to unveil the molecular mechanisms underlying the corresponding biological effects and therapeutic benefits reported above. To this regard, particular attention should be paid to the effects of Avns on the intestinal microbiome, as this has been recognized as a fundamental player in human health and disease, affecting a variety of conditions such as host energy balance and immune responses [ ], and has been recently implicated also in the pathogenesis of CCM disease, suggesting that manipulation of the bacterial microbiome may indeed be an effective therapeutic approach [ ].


It is therefore important that future foodomics investigations will also include information from gut-residing bacteria and consequent modulation of the gut-brain axis. Go to: 9.

diabetes obesity and metabolism a journal of pharmacology and therapeutics működési diabetes kezelésére gyermekeknél

Redox Proteomics for Detailing Chemical Modifications Hampered by Avenanthramides in Chronic Diseases Oxidative and nitrosative stresses, due to an imbalance between the generation of ROS and reactive nitrogen species RNSand the antioxidant defense capacity of the organism, are important pathophysiological events contributing to the onset and progression of several human pathologies, including cardiovascular diseases and metabolic syndromes [].

In particular, hundreds of adducts of distinct nature have been identified in proteins as a result of the reaction of ROS and RNS with chemical groups present in amino acid side chain [ ]. Gel-based and gel-free redox proteomics techniques often use liquid chromatography coupled to mass spectrometry as the major platform to achieve the goal of identifying and fully characterizing oxidized and nitrosized target proteomes. Once identified, oxidized and nitrosized proteins can be placed in specific molecular pathways to provide insights into affected molecular and cellular functions associated with human diseases.

Whenever inserted in perturbative experiment pipelines, redox proteomics approaches are now allowing a monitoring of the degree of corresponding body tissue damage and the response to pharmacological therapies.

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  3. Беккер понимал, что через несколько секунд его преследователь побежит назад и с верхних ступеней сразу же увидит вцепившиеся в карниз пальцы.

In this context, pioneering experiments have been performed to evaluate the impact of i excessive caloric intake on oxidized and carbonylated proteins from adipose tissues of healthy men [ ]; ii fasting on Cys-oxidized proteins from healthy animals [ ]; iii high-fat and high-sucrose diet on carbonylated proteins from tissues and body fluids of healthy animals [ ]; iv the assumption of glutathione derivatives on Tyr-nitrated proteins from brain-injured animal models [ ]; v antioxidant-fortified diet on nyomás cukorbetegség kezelésére and Tyr-nitrated proteins from brain tissues of animal models of AD [ ]; vi high-fat and alcohol diet on carbonylated and Cys-oxidized proteins from tissues and body fluids of fatty liver disease patients and related animal models [ — ].

In the close future, it is hypothesized that redox proteomics studies will also be performed on organisms or animal models of human diseases fed with oat compounds and derivatives, including isolated natural and recombinant Avns, in order to evaluate the capacity of such nutraceuticals to modulate oxidized and nitrosized proteomes in target tissues and body fluids. Go to: Concluding Remarks It is generally accepted that antioxidants exert health-promoting effects by scavenging intracellular ROS; thus, their consumption as food additives and nutraceuticals has been greatly encouraged.

Awarded works of the 15th National Conference of Student Researchers. Ministry of Education. Institute of Scientific Information, Budapest. Thesis of M. Colloid Chem.

Nonetheless, to date, there is little clinical evidence for the long-term benefits of most antioxidants, while there are even alarms of health risks consequent to supplementation of lipophilic antioxidants [ 68 ]. Accordingly, the existence of a physiological role of specific ROS concentrations can explain the negative results from clinical trials, where large doses of exogenously-administered antioxidants or hyperactivation of antioxidant pathways with electrophilic therapeutics failed to improve outcomes of oxidative stress-related diseases or resulted even deleterious [ 6367, ].

Indeed, it is now well established that redox reactions bear the Janus faceted feature of promoting both physiological signaling responses and pathological cues in all biological systems, as well as that endogenous antioxidant molecules and mechanisms participate in both scenarios [ 6367 ]. Consistently, emerging evidence demonstrates that only intermediate levels of major regulators of antioxidant responses are beneficial, although both the low and high concentration thresholds for physiological versus pathological effects may vary largely depending on genetic and environmental factors and the cellular context [ ].

Thus, given that most of the emerging therapeutic compounds with antioxidant properties influence redox-sensitive mechanisms, both their low and high concentration thresholds for physiological versus pathological effects have to be carefully considered. In this light, further studies are necessary to fully address the beneficial effects of Avns in human health, including antioxidant, antiproliferative, anti-inflammatory, antiaging, and anticancer activities Figure 2.

In particular, useful insights could be derived from foodomics and redox proteomics studies aimed at a comprehensive characterization of molecules and mechanisms that mediate the pleiotropic effects of Avns in cellular and animal models of human diseases, including oxidative posttranslational modifications of structural and regulatory proteins. Moreover, novel therapeutic approaches, including combinatorial therapy and nanotechnology-based targeted drug delivery, are encouraged in order to allow site-directed application, appropriate dosing regimens, pharmacological repair of oxidized biomolecules, and triggering of endogenous antioxidant response systems, which could also be guided by the identification of predictive biomarkers.