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Volume 21, Issue 2,
, Pages 270-276
Author links open overlay panelThomas H.JukesPh.D.
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- HM EvansThe pioneer history of vitamin E
- HM Evans et al.
J Biol Chem
- TH JukesHistorical perspectives: The prevention and conquest of scurvy, beri-beri, and pellagra
- A Comfort et al.
Effect of ethoxyquin on the longevity of C3H mice
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- Selenocysteine in mammalian thioredoxin reductase and application of ebselen as a therapeutic
2018, Free Radical Biology and Medicine
Thioredoxin system is a ubiquitous disulfide reductase system evolutionarily conserved through all living organisms. It contains thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH. TrxR can use NADPH to reduce Trx which passes the reducing equivalent to its downstream substrates involved in various biomedical events, such as ribonucleotide reductase for deoxyribonucleotide and DNA synthesis, or peroxiredoxins for counteracting oxidative stress. Obviously, TrxR stays in the center of the system to maintain the electron flow. Mammalian TrxR contains a selenocysteine (Sec) in its active site, which is not present in the low molecular weight prokaryotic TrxRs. Due to the special property of Sec, mammalian TrxR employs a different catalytic mechanism from prokaryotic TrxRs and has a broader substrate-spectrum. On the other hand, Sec is easily targeted by electrophilic compounds which inhibits the TrxR activity and may turn TrxR into an NADPH oxidase. Ebselen, a synthetic seleno-compound containing selenazol, has been tested in several clinical studies. In mammalian cells, ebselen works as a GSH peroxidase mimic and mainly as a peroxiredoxin mimic via Trx and TrxR to scavenge hydrogen peroxide and peroxynitrite. In prokaryotic cells, ebselen is an inhibitor of TrxR and leads to elevation of reactive oxygen species (ROS). Recent studies have made use of the difference and developed ebselen as a potential antibiotic, especially in combination with silver which enables ebselen to kill multi-drug resistant Gram-negative bacteria. Collectively, Sec is important for the biological functions of mammalian TrxR and distinguishes it from prokaryotic TrxRs, therefore it is a promising drug target.
- Vitamin E, antioxydants and atherosclerosis
1994, La Revue de medecine interne
L'athérosclérose est un processus dans lequel les facteurs lipidiques et cellulaires sont intriqués. Les LDL, lorsqu'elles sont oxydées, sont catabolisées par la voie des macrophages conduisant aux cellules spumeuses constitutives de la strie lipidique, lésion initiale de l'athérome, et ont des effets cytotoxiques, chimiotactiques… De nombreux systèmes de protection contre les radicaux libres et les processus d'oxydation existent, en particulier les antioxydants vitaminiques et d'autres antioxydants naturels. Après un rappel de leurs mécanismes d'action, les données épidémiologiques, expérimentales et cliniques sont passées en revue. Il apparaît aujourd'hui indispensable de prendre en compte ces facteurs dans la prévention et le traitement de l'athérosclérosclérose et des dyslipidémies. De nombreuses questions persistent, concernant notamment l'appréciation de la susceptibilité à l'oxydation. Des essais d'intervention sont attendus pour conclure définitivement sur les indications thérapeutiques, nutritionnelles et médicamenteuses.See Also21st Century | Latest News, Photos & VideosRadiators Vs. Forced Air: The Great Heating DebateAll You Need to Know about Applying for UK Visa from UAEThe 5 Biggest Problems with Fiber Cement Siding
Atherosclerosis is a process in which lipid and factors are mixed. When LDL are oxydized, they are catabolized by the macrophage's pathway, leading to foam cells which constitute the fatty streak, the earliest lesion in atherogenesis, and they have cytotoxic, chemotactic effects. Many protective devices against free radicals and oxydation mechanisms exist, particularly antioxydant vitamins and other natural dietary antioxydants. After a brief recall of their mechanisms, epidemiological, experimental and clinical data are reviewed. To day it seems necessary to take into consideration these factors in prevention and therapeutic of atherosclerosis and dylipidaemia. Many inquiries keep going, particularly about susceptibly of LDL to oxydation. One is waiting for intervention surveys in order to conclude about nutritional and medical treatments.
Why Nature Chose Selenium
2016, ACS Chemical Biology
Chemical compositions and effects of aqueous extract of Cissus multistriata on some biochemical parameters in albino rats
2009, International Journal of PharmTech Research
Oxidative stress status in patients with diabetes mellitus: Relationship to diet
2003, European Journal of Clinical Nutrition
Identification and production of local carotene-rich foods to combat vitamin A malnutrition
1997, European Journal of Clinical Nutrition(Video) The New Evolution Diet - Episode 2
Research articleCarotenes and xanthophylls as antioxidants
Handbook of Antioxidants for Food Preservation, 2015, pp. 17-50
The major carotenes and xanthophylls, their occurrence in foods, commercial production, application, and health effects are discussed. The antioxidant activity in carotenoids is the most cited mode of action in reducing the risk of chronic degenerative diseases, but other mechanisms are increasingly being reported. β-Carotene, lycopene, lutein, and zeaxanthin are the most investigated carotenoids in terms of human health, followed by astaxanthin and β-cryptoxanthin. The scientific evidence is strongest for the effects of lutein and zeaxanthin in retinal macular degeneration and cataracts, and for tomato and tomato products in prostate cancer. The latter is widely attributed to lycopene, but other tomato phytochemicals may also be involved.
Research articlePINK1-Parkin signaling in Parkinson’s disease: Lessons from Drosophila
Neuroscience Research, Volume 159, 2020, pp. 40-46
The mitochondrial protein kinase PINK1 activates Parkin ubiquitin ligase by phosphorylating Parkin and ubiquitin, which are required for mitochondrial maintenance in dopaminergic (DA) neurons whose degeneration leads to the development of Parkinson’s disease (PD). Loss of PINK1 and Parkin leads to mitochondrial degeneration and abnormal wing posture in Drosophila. Modifier screening using the Drosophila wing phenotype showed that the inactivation of Miro, a mitochondrial adaptor protein, suppresses the phenotype caused by mitochondrial degeneration. When activated by PINK1, Parkin suppresses mitochondrial transport by reducing Miro levels in Drosophila DA neurons. In human DA neurons, PINK1-Parkin signaling also regulates axonal mitochondrial re-distribution in response to reduced mitochondrial membrane potential, which is impaired in the DA neurons of patients with PINK1 and Parkin mutations. Phospho-ubiquitin signals amplified by PINK1 and Parkin are stronger in DA neurons than other neurons, suggesting that PINK1-Parkin signaling is particularly important for DA neuron activity. Moreover, the recently identified PD-associated protein CHCHD2 may ensure proper electron transfer during mitochondrial respiration. The genetic interaction between PINK1/Parkin and CHCHD2 in Drosophila indicates that they are not directly associated and CHCHD2-linked PD exhibits a very different pathology to PINK1/Parkin PD. I suggest a complex pathogenesis for mitochondrial dysregulation in PD.
Research articleAntioxidants with two faces toward cancer
Life Sciences, Volume 258, 2020, Article 118186
Antioxidants are essential in preventing the formation and suppressing the activities of reactive nitrogen and oxygen species. The aim of this study was to review the role of antioxidants in cancer development or prevention. Antioxidants are believed to prevent and treat various types of malignancies. Currently, natural antioxidant compounds have been generally consumed to prevent and treat cancers. Certainly, phenolic compounds extracted from medicinal plants have opened a new prospect with respect to the prevention and treatment of cancers due to having antioxidant characteristics. However, some recently published studies have revealed that antioxidant compounds do not indicate absolute anti-tumor properties. Some antioxidants are helpful in cancer initiation and progression. Taken together, antioxidants demonstrate a two-faced nature toward cancer. However, it is required to conduct further cell culture and in vivo studies to confirm the exact role of antioxidants and then use them for efficient cancer treatments.
Research articleAdministration of antioxidants in cancer: debate of the decade
Drug Discovery Today, Volume 23, Issue 4, 2018, pp. 763-770(Video) Scientist Explains: Food and Evolution; how our diet made us human!
Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal models opposing human clinical trials discourage the concurrent administration of antioxidants ostensibly owing to the possibility of tumor protection and reduced survival.
Research articleImproved biological activity of a single chain antibody fragment against human epidermal growth factor receptor 2 (HER2) expressed in the periplasm of Escherichia coli
Protein Expression and Purification, Volume 116, 2015, pp. 66-74
A novel monoclonal antibody against human epidermal growth factor receptor 2 (HER2), i.e., pertuzumab (Perjeta®) developed by Genentech, has been verified to be effective in treating metastatic HER2-overexpressing breast cancer. The fact that the presence of the Fc region of the anti-HER2 is uncritical for growth inhibition of tumor cells suggests the potential biological activity of the associated antibody fragments. In the present study, we report functional expression of anti-HER2his-scFv, a single-chain variable fragment (scFv) derived from pertuzumab, in the periplasm of Escherichia coli and its purification. Biological activity of the soluble scFv produced in this manner was characterized using immunofluorescent staining, immunocytochemistry, flow cytometry and cytotoxicity assay. The effect of anti-HER2his-scFv on HER2 dimerization was also assessed by tyrosine kinase assay. It was observed that the purified scFv had a high specificity and affinity to HER2 receptors expressed on the surface of tumor cells with a selective cytotoxic effect on HER2-overexpressing SK-OV-3 cells. In addition, anti-HER2his-scFv was able to suppress phosphorylation of HER2 in the presence of heregulin. The results suggest that anti-HER2his-scFv can be a potential candidate for various therapeutic and diagnosis applications.
Research articlePhosphodiesterase-5 Inhibitor PF-03049423 Effect on Stroke Recovery: A Double-Blind, Placebo-Controlled Randomized Clinical Trial
Journal of Stroke and Cerebrovascular Diseases, Volume 25, Issue 3, 2016, pp. 642-649
The therapeutic potential of phosphodiesterase-5 inhibitor PF-03049423 was evaluated in a phase 2, multicenter, randomized, double-blind, placebo-controlled study of subjects with acute ischemic stroke (Clinical Trial Registration Information: http://www.clinicaltrials.gov, unique identifier: NCT01208233; http://www.clinicaltrialsregister.eu, EudraCT number: 2010-021414-32).
Subjects (N = 70) received PF-03049423 6 mg (or placebo, N = 67) once daily, orally, commencing between 24 and 78 hours of stroke onset, and continuing for 90 days. Postbaseline efficacy assessments were performed on Days 7, 14, 30, 60, and 90. Modified Rankin Scale (mRS), Barthel Index, National Institutes of Health Stroke Scale, Box and Blocks Test, Hand-Grip Strength Test, 10-Meter Walk Test, Repeatable Battery Assessment of Neuropsychological Status Naming and Coding Subtests, Line Cancellation Test, and Recognition Memory Test were administered to evaluate poststroke recovery. The primary endpoint was the mRS responder rate (score 0-2 at Day 90). The study included a planned interim analysis of efficacy data.
The primary efficacy analysis using logistic regression showed no statistically significant difference between PF-03049423 6 mg and placebo (responder rate of 42.6% and 46.2%, respectively). Although PF-03049423 showed a satisfactory safety and tolerability profile, no signal of efficacy emerged from any of the outcome measures.
PF-03049423 showed no therapeutic potential for acute ischemic stroke.
Copyright © 1992 Published by Elsevier Inc.
Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Diets high in vegetables and fruits, which are good sources of antioxidants, have been found to be healthy; however, research has not shown antioxidant supplements to be beneficial in preventing diseases.Is there any science behind antioxidants? ›
Epidemiological prospective studies show that higher intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of chronic oxidative stress-related diseases like cardiovascular diseases, cancer, and deaths from all causes.Which nutrients are the 4 antioxidants? ›
Antioxidants are found in certain foods and may prevent some of the damage caused by free radicals by neutralising them. These include the nutrient antioxidants, vitamins A, C and E, and the minerals copper, zinc and selenium.What is antioxidants and its function? ›
Antioxidants are substances that may protect your cells against free radicals, which may play a role in heart disease, cancer and other diseases. Free radicals are molecules produced when your body breaks down food or when you're exposed to tobacco smoke or radiation.What are the three types of antioxidants? ›
Antioxidants can be divided into three groups by their mechanism: (1) primary antioxidants, which function essentially as free radical terminators (scavengers); (2) secondary antioxidants, which are important preventive antioxidants that function by retarding chain initiation; and (3) tertiary antioxidants, which are ...What is the most powerful antioxidant? ›
As mentioned above, a-tocopherol is well recognized and accepted as the nature's most effective lipid-soluble, chain-breaking antioxidant, protecting cellular membranes from being attacked by lipid peroxyl radicals. Vitamin E prevents the propagation of lipid peroxyl radicals in cellular membranes.Does the body absorb antioxidants? ›
Intestine does not easily absorb antioxidants
“The concentration of polyphenols and other antioxidants in the blood are often so low that they don't have an effect,” he says. “Many [antioxidants] have difficulty passing through fat-loving membranes because they are relatively polar.
Answer. Yes they do. If we take, for example, vitamin C, which is actually ascorbic acid, which in theory shouldn't be broken down in an acid environment. We do rely on absorbing vitamins to remain healthy, so the body must have evolved mechanisms to absorb these without them being broken down.Can too much antioxidants be harmful? ›
Taking antioxidants in excess can overwhelm free radicals that cells use to talk to one another and function properly, which Kehrer said is probably part of the reason why taking too many isn't as good as taking the right amount.What is another name for antioxidants? ›
- rust inhibitor.
- glutathione peroxidase.
Broccoli, spinach, carrots and potatoes are all high in antioxidants, and so are artichokes, cabbage, asparagus, avocados, beetroot, radish, lettuce, sweet potatoes, squash, pumpkin, collard greens and kale.What are antioxidants in simple terms? ›
(AN-tee-OK-sih-dent) A substance that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging.What foods are highest in antioxidants? ›
Broccoli, spinach, carrots and potatoes are all high in antioxidants, and so are artichokes, cabbage, asparagus, avocados, beetroot, radish, lettuce, sweet potatoes, squash, pumpkin, collard greens and kale.What are natural antioxidants? ›
Natural antioxidants are primarily phenolics that may occur in all parts of plants , such as fruits, vegetables, nuts, seeds, leaves, roots, and barks. In the recent past, some toxicological studies regarding the use of synthetic antioxidants have shown their unwanted or adverse effects.Where antioxidants are found? ›
Antioxidants are found in many foods, including fruits and vegetables. They are also available as dietary supplements. Examples of antioxidants include: Beta-carotene.