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1.
Structural insights into the mechanism of oxidative activation of heme-free H-NOX from Vibrio cholerae.
Mukhopadhyay, R, Chacón, KN, Jarvis, JM, Talipov, MR, Yukl, ET
The Biochemical journal. 2020;(6):1123-1136
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Abstract
Bacterial heme nitric oxide/oxygen (H-NOX) domains are nitric oxide (NO) or oxygen sensors. This activity is mediated through binding of the ligand to a heme cofactor. However, H-NOX from Vibrio cholerae (Vc H-NOX) can be easily purified in a heme-free state that is capable of reversibly responding to oxidation, suggesting a heme-independent function as a redox sensor. This occurs by oxidation of Cys residues at a zinc-binding site conserved in a subset of H-NOX homologs. Remarkably, zinc is not lost from the protein upon oxidation, although its ligation environment is significantly altered. Using a combination of computational and experimental approaches, we have characterized localized structural changes that accompany the formation of specific disulfide bonds between Cys residues upon oxidation. Furthermore, the larger-scale structural changes accompanying oxidation appear to mimic those changes observed upon NO binding to the heme-bound form. Thus, Vc H-NOX and its homologs may act as both redox and NO sensors by completely separate mechanisms.
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Polyphenols: Potential Beneficial Effects of These Phytochemicals in Athletes.
D'Angelo, S
Current sports medicine reports. 2020;(7):260-265
Abstract
An athlete's dietary requirements depend on several aspects, including the environment, the sport, and the athlete's goals. Although it is recognized that regular exercise improves muscle performance and energy metabolism, unaccustomed or excessive exercise may cause cell damage and impair muscle function by triggering tissue inflammation and oxidative stress. Supplement use among athletes is widespread and recently new attention has been applied to polyphenols. Polyphenols are a class of organic chemical compounds, mainly found in plants, characterized by the presence of multiples of phenol structural units, and over recent decades, special attention has been paid to the healthy role of fruit-derived polyphenols in the human diet. This article will summarize latest knowledge on polyphenolic compounds that have been demonstrated both to exert an effect in exercise-induced muscle damage and to play a biological/physiological role in improving physical performance.
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Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life.
Baldan Ferrari, G, Coelho França Quintanilha, J, Berlofa Visacri, M, Oliveira Vaz, C, Cursino, MA, Sampaio Amaral, L, Brito Bastos, , Pereira, TT, de Oliveira Guarnieri, JP, de Godoy Torso, N, et al
Anti-cancer drugs. 2020;(5):523-527
Abstract
The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.
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The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial.
Heshmati, J, Golab, F, Morvaridzadeh, M, Potter, E, Akbari-Fakhrabadi, M, Farsi, F, Tanbakooei, S, Shidfar, F
Diabetes & metabolic syndrome. 2020;(2):77-82
Abstract
BACKGROUND & AIMS Curcumin is a biologically active phytochemical ingredient found in turmeric and has antioxidant pharmacologic actions that may benefit patients with polycystic ovarian syndrome (PCOS). The aim in this trial was to evaluate the efficacy of curcumin supplementation on oxidative stress enzymes, sirtuin-1 (SIRT1) and Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) gene expression in PCOS patients. METHODS Seventy-two patients with PCOS were recruited for this randomized, double-blinded, clinical trial. Thirty-six patients received curcumin, 1500 mg (three times per day), and 36 patients received placebo for 3 months. Gene expression of SIRT1, PGC1α and serum activity of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) enzymes were evaluated at the beginning of trial and at 3-month follow-up. RESULTS Sixty-seven patients with PCOS completed the trial. Curcumin supplementation significantly increased gene expression of PGC1α (p = 0.011) and activity of the Gpx enzyme (p = 0.045). Curcumin also non-significantly increased gene expression of SIRT1 and activity of the SOD enzyme. CONCLUSIONS Curcumin seems to be an efficient reducer of oxidative stress related complications in patients with PCOS. Further studies on curcumin should strengthen our findings.
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Mechanisms of sensing and response to proteotoxic stress.
Santiago, AM, Gonçalves, DL, Morano, KA
Experimental cell research. 2020;(2):112240
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Abstract
Cells are continuously subject to various stresses, battling both exogenous insults as well as toxic by-products of normal cellular metabolism and nutrient deprivation. Throughout the millennia, cells developed a core set of general stress responses that promote survival and reproduction under adverse circumstances. Past and current research efforts have been devoted to understanding how cells sense stressors and how that input is deciphered and transduced, resulting in stimulation of stress management pathways. A prime element of cellular stress responses is the increased transcription and translation of proteins specialized in managing and mitigating distinct types of stress. In this review, we focus on recent developments in our understanding of cellular sensing of proteotoxic stressors that impact protein synthesis, folding, and maturation provided by the model eukaryote the budding yeast, Saccharomyces cerevisiae, with reference to similarities and differences with other model organisms and humans.
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The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta-analysis of clinical trials.
Jalali, M, Mahmoodi, M, Moosavian, SP, Jalali, R, Ferns, G, Mosallanezhad, A, Imanieh, MH, Mosallanezhad, Z
Phytotherapy research : PTR. 2020;(8):1723-1733
Abstract
The present systematic review and meta-analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C-reactive protein), TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random-effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full-text articles that included 25 separate studies were included to the meta-analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF-α, IL-6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.
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A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, clinical trial.
Hariri, M, Gholami, A, Mirhafez, SR, Bidkhori, M, Sahebkar, A
Complementary therapies in medicine. 2020;:102447
Abstract
BACKGROUND The enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes. MATERIAL AND METHODS in this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2' -deoxyguanosine (8-OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively. RESULT Analysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8-OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group. CONCLUSION Curcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.
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Cardioprotective Effects of Dietary Phytochemicals on Oxidative Stress in Heart Failure by a Sex-Gender-Oriented Point of View.
Komici, K, Conti, V, Davinelli, S, Bencivenga, L, Rengo, G, Filippelli, A, Ferrara, N, Corbi, G
Oxidative medicine and cellular longevity. 2020;:2176728
Abstract
Dietary phytochemicals are considered an innovative strategy that helps to reduce cardiovascular risk factors. Some phytochemicals have been shown to play a beneficial role in lipid metabolism, to improve endothelial function and to modify oxidative stress pathways in experimental and clinical models of cardiovascular impairment. Importantly, investigation on phytochemical effect on cardiac remodeling appears to be promising. Nowadays, drug therapy and implantation of devices have demonstrated to ameliorate survival. Of interest, sex-gender seems to influence the response to HF canonical therapies. In fact, starting by the evidence of the feminization of world population and the scarce efficacy and safety of the traditional drugs in women, the search of alternative therapeutic tools has become mandatory. The aim of this review is to summarize the possible role of dietary phytochemicals in HF therapy and the evidence of a different sex-gender-oriented response.
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Adjunct N-Acetylcysteine Treatment in Hospitalized Patients With HIV-Associated Tuberculosis Dampens the Oxidative Stress in Peripheral Blood: Results From the RIPENACTB Study Trial.
Safe, IP, Amaral, EP, Araújo-Pereira, M, Lacerda, MVG, Printes, VS, Souza, AB, Beraldi-Magalhães, F, Monteiro, WM, Sampaio, VS, Barreto-Duarte, B, et al
Frontiers in immunology. 2020;:602589
Abstract
Tuberculosis (TB) still causes significant morbidity and mortality worldwide, especially in persons living with human immunodeficiency virus (HIV). This disease is hallmarked by persistent oxidative stress and systemic inflammation. N-acetylcysteine (NAC), a glutathione (GSH) precursor, has been shown in experimental models to limit Mycobacterium tuberculosis infection and disease both by suppression of the host oxidative response and through direct antimicrobial activity. In a recent phase II randomized clinical trial (RIPENACTB study), use of NAC as adjunct therapy during the first two months of anti-TB treatment was safe. Whether adjunct NAC therapy of patients with TB-HIV coinfection in the context of anti-TB treatment could directly affect pro-oxidation and systemic inflammation has not been yet formally demonstrated. To test this hypothesis, we leveraged existing data and biospecimens from the RIPENACTB trial to measure a number of surrogate markers of oxidative stress and of immune activation in peripheral blood of the participants at pre-treatment and at the day 60 of anti-TB treatment. Upon initiation of therapy, we found that the group of patients undertaking NAC exhibited significant increase in GSH levels and in total antioxidant status while displaying substantial reduction in lipid peroxidation compared to the control group. Only small changes in plasma concentrations of cytokines were noted. Pharmacological improvement of the host antioxidant status appears to be a reasonable strategy to reduce TB-associated immunopathology.
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A Double-Blind, Cross-Over Study to Examine the Effects of Maritime Pine Extract on Exercise Performance and Postexercise Inflammation, Oxidative Stress, Muscle Soreness, and Damage.
Aldret, RL, Bellar, D
Journal of dietary supplements. 2020;(3):309-320
Abstract
The purpose of the present study was to examine whether 14 days of supplementation with maritime pine extract leading up to and following an exercise test would increase performance and reduce biomarkers associated with muscle damage, inflammation, and oxidative stress. The study used a double-blind, placebo-controlled, cross-over design. Twenty apparently healthy young male participants ingested either 800 mg pine bark extract or placebo for 14 days prior to the first exercise trial and for 2 days postexercise. On the exercise day, participants submitted a pre-exercise blood sample then completed a VO2 peak test until volitional failure. A postexercise blood sample was collected 1 hour after completion of exercise. Participants returned at 24 and 48 hours after the exercise testing for measures of muscle pain in the lower body using an algometer. Participants then had a 7-day washout period before beginning to cross over to the alternate treatment. Analysis via ordinal regression demonstrated a significant difference in oxidative stress in the maritime pine extract group compared to placebo (ChiSq = 2.63; p = 0.045). Maritime pine extract was effective at affording protection from oxidative stress postexercise. Further work should be undertaken to evaluate the findings with other exercise modes or in participants with known metabolic syndrome.