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1.
Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases.
Bernatoniene, J, Kazlauskaite, JA, Kopustinskiene, DM
International journal of molecular sciences. 2021;(11)
Abstract
Isoflavones are phytoestrogens of plant origin, mostly found in the members of the Fabaceae family, that exert beneficial effects in various degenerative disorders. Having high similarity to 17-β-estradiol, isoflavones can bind estrogen receptors, scavenge reactive oxygen species, activate various cellular signal transduction pathways and modulate growth and transcription factors, activities of enzymes, cytokines, and genes regulating cell proliferation and apoptosis. Due to their pleiotropic activities isoflavones might be considered as a natural alternative for the treatment of estrogen decrease-related conditions during menopause. This review will focus on the effects of isoflavones on inflammation and chronic degenerative diseases including cancer, metabolic, cardiovascular, neurodegenerative diseases, rheumatoid arthritis and adverse postmenopausal symptoms.
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2.
Bisphenol A and Male Fertility: Myths and Realities.
Castellini, C, Totaro, M, Parisi, A, D'Andrea, S, Lucente, L, Cordeschi, G, Francavilla, S, Francavilla, F, Barbonetti, A
Frontiers in endocrinology. 2020;:353
Abstract
Bisphenol A (BPA) represents the main chemical monomer of epoxy resins and polycarbonate plastics. The environmental presence of BPA is widespread, and it can easily be absorbed by the human body through dietary and transdermal routes, so that more than 90% of the population in western countries display detectable BPA levels in the urine. As BPA is qualified as an endocrine disruptor, growing concern is rising for possible harmful effects on human health. This review critically discusses the available literature dealing with the possible impact of BPA on male fertility. In rodent models, the in vivo exposure to BPA negatively interfered with the regulation of spermatogenesis throughout the hypothalamic-pituitary-gonadal axis. Furthermore, in in vitro studies, BPA promoted mitochondrial dysfunction and oxidative/apoptotic damages in spermatozoa from different species, including humans. To date, the claimed clinical adverse effects on male fertility are largely based on the results from studies assessing the relationship between urinary BPA concentration and conventional semen parameters. These studies, however, produced controversial evidence due to heterogeneity in the extent of BPA exposure, type of population, and enrollment setting. Moreover, the cause-effect relationship cannot be established due to the cross-sectional design of the studies as well as the large spontaneous between- and within-subject variability of semen parameters. The best evidence of an adverse effect of BPA on male fertility would be provided by prospective studies on clinically relevant endpoints, including natural or medically assisted pregnancies among men either with different exposure degrees (occupational/environmental) or with different clinical conditions (fertile/subfertile).
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3.
Antioxidant treatments for schizophrenia.
Magalhães, PV, Dean, O, Andreazza, AC, Berk, M, Kapczinski, F
The Cochrane database of systematic reviews. 2016;(2):CD008919
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Abstract
BACKGROUND There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. OBJECTIVES To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. SEARCH METHODS We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. DATA COLLECTION AND ANALYSIS We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. AUTHORS' CONCLUSIONS Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.
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4.
Treatment of Severe Alcoholic Hepatitis.
Thursz, M, Morgan, TR
Gastroenterology. 2016;(8):1823-34
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Abstract
Alcoholic hepatitis (AH) is a syndrome of jaundice and liver failure that occurs in a minority of heavy consumers of alcohol. The diagnosis usually is based on a history of heavy alcohol use, findings from blood tests, and exclusion of other liver diseases by blood and imaging analyses. Liver biopsy specimens, usually collected via the transjugular route, should be analyzed to confirm a diagnosis of AH in patients with an atypical history or presentation. The optimal treatment for patients with severe AH is prednisolone, possibly in combination with N-acetyl cysteine. At present, only short-term increases in survival can be expected-no treatment has been found to increase patient survival beyond 3 months. Abstinence is essential for long-term survival. New treatment options, including liver transplantation, are being tested in trials and results eagerly are awaited.
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5.
Pharmacologic neuroprotective strategies in neonatal brain injury.
Juul, SE, Ferriero, DM
Clinics in perinatology. 2014;(1):119-31
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Abstract
This article explains the mechanisms underlying choices of pharmacotherapy for hypoxic-ischemic insults of both preterm and term babies. Some preclinical data are strong enough that clinical trials are now underway. Challenges remain in deciding the best combination therapies for each age and insult.
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6.
Molecular mechanisms of production and scavenging of reactive oxygen species by photosystem II.
Pospíšil, P
Biochimica et biophysica acta. 2012;(1):218-31
Abstract
Photosystem II (PSII) is a multisubunit protein complex in cyanobacteria, algae and plants that use light energy for oxidation of water and reduction of plastoquinone. The conversion of excitation energy absorbed by chlorophylls into the energy of separated charges and subsequent water-plastoquinone oxidoreductase activity are inadvertently coupled with the formation of reactive oxygen species (ROS). Singlet oxygen is generated by the excitation energy transfer from triplet chlorophyll formed by the intersystem crossing from singlet chlorophyll and the charge recombination of separated charges in the PSII antenna complex and reaction center of PSII, respectively. Apart to the energy transfer, the electron transport associated with the reduction of plastoquinone and the oxidation of water is linked to the formation of superoxide anion radical, hydrogen peroxide and hydroxyl radical. To protect PSII pigments, proteins and lipids against the oxidative damage, PSII evolved a highly efficient antioxidant defense system comprising either a non-enzymatic (prenyllipids such as carotenoids and prenylquinols) or an enzymatic (superoxide dismutase and catalase) scavengers. It is pointed out here that both the formation and the scavenging of ROS are controlled by the energy level and the redox potential of the excitation energy transfer and the electron transport carries, respectively. The review is focused on the mechanistic aspects of ROS production and scavenging by PSII. This article is part of a Special Issue entitled: Photosystem II.
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7.
Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics.
Villamena, FA, Das, A, Nash, KM
Future medicinal chemistry. 2012;(9):1171-207
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Abstract
Nitrone therapeutics has been employed in the treatment of oxidative stress-related diseases such as neurodegeneration, cardiovascular disease and cancer. The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. However, the specific mechanism of nitrone bioactivity remains unclear. In this review, we present a variety of nitrone chemistry and biological activity that could be implicated for the nitrone's pharmacological activity. The chemistries of spin trapping and spin adduct reveal insights on the possible roles of nitrones for altering cellular redox status through radical scavenging or nitric oxide donation, and their biological effects are presented. An interdisciplinary approach towards the development of novel synthetic antioxidants with improved pharmacological properties encompassing theoretical, synthetic, biochemical and in vitro/in vivo studies is covered.
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Micronutrients, N-acetyl cysteine, probiotics and prebiotics, a review of effectiveness in reducing HIV progression.
Hummelen, R, Hemsworth, J, Reid, G
Nutrients. 2010;(6):626-51
Abstract
Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use.
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Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis.
Brien, S, Prescott, P, Bashir, N, Lewith, H, Lewith, G
Osteoarthritis and cartilage. 2008;(11):1277-88
Abstract
OBJECTIVE Conventional treatment of osteoarthritis (OA) with non-steroidal anti-inflammatory drugs is associated with serious gastrointestinal side effects and in view of the recent withdrawal of some cyclo-oxygenase-2 inhibitors, identifying safer alternative treatment options is needed. The objective of this systematic review is to evaluate the existing evidence from randomised controlled trials of two chemically related nutritional supplements, dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of OA to determine their efficacy and safety profile. METHODS The electronic databases [Cochrane Library, Medline, Embase, Amed, Cinahl and NeLH (1950 to November 2007)] were searched. The search strategy combined terms: osteoarthritis, degenerative joint disorder, dimethyl sulfoxide, DMSO, methylsulfonylmethane, MSM, clinical trial; double-blind, single blind, RCT, placebo, randomized, comparative study, evaluation study, control. Inclusion and exclusion criteria were applied. Data were extracted and quality was assessed using the JADAD scale. RESULTS Six studies were included [evaluating a total of 681 patients with OA of the knee for DMSO (N=297 on active treatment); 168 patients for MSM (N=52 on active treatment)]. Two of the four DMSO trials, and both MSM trials reported significant improvement in pain outcomes in the treatment group compared to comparator treatments, however, methodological issues and concerns over optimal dosage and treatment period, were highlighted. CONCLUSION No definitive conclusion can currently be drawn for either supplement. The findings from all the DMSO studies need to be viewed with caution because of poor methodology including; possible unblinding, and questionable treatment duration and dose. The data from the more rigorous MSM trials provide positive but not definitive evidence that MSM is superior to placebo in the treatment of mild to moderate OA of the knee. Further studies are now required to identify both the optimum dosage and longer-term safety of MSM and DMSO, and definitive efficacy trials.
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10.
Primary antioxidant free radical scavenging and redox signaling pathways in higher plant cells.
Shao, HB, Chu, LY, Lu, ZH, Kang, CM
International journal of biological sciences. 2007;(1):8-14
Abstract
Antioxidants in plant cells mainly include glutathione, ascorbate, tocopherol, proline, betaine and others, which are also information-rich redox buffers and important redox signaling components that interact with cellular compartments. As an unfortunate consequence of aerobic life for higher plants, reactive oxygen species (ROS) are formed by partial reduction of molecular oxygen. The above enzymatic and non-enzymatic antioxidants in higher plant cells can protect their cells from oxidative damage by scavenging ROS. In addition to crucial roles in defense system and as enzyme cofactors, antioxidants influence higher plant growth and development by modifying processes from miotosis and cell elongation to senescence and death. Most importantly, they provide essential information on cellular redox state, and regulate gene expression associated with biotic and abiotic stress responses to optimize defense and survival. An overview of the literature is presented in terms of primary antioxidant free radical scavenging and redox signaling in plant cells. Special attention is given to ROS and ROS-anioxidant interaction as a metabolic interface for different types of signals derived from metabolisms and from the changing environment. This interaction regulates the appropriate induction of acclimation processes or execution of cell death programs, which are the two essential directions for higher plant cells.