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Frontiers in Bioscience (Landmark... Jan 2009The balance between production and clearance of reactive species is essential for cell survival. Antioxidant cellular systems evolved to maintain a redox homeostasis... (Review)
Review
The balance between production and clearance of reactive species is essential for cell survival. Antioxidant cellular systems evolved to maintain a redox homeostasis under different physiological and pathological conditions. Therefore, many authors aim at better understanding the mechanisms and functions of cellular antioxidant components and their relationships between each other and with more general cell functions. Nonetheless, the definition of an "antioxidant system" is a wide and sometimes relative concept, and there is no consensus regarding the necessary requisites for classifying a cell functional component into such category. Here, we suggest a list of human antioxidant genes comprehending all gene products fulfilling specific inclusion criteria, such as antioxidant enzymatic function, participation in redox reactions and other molecular interactions directly related to antioxidant activity. The criteria are discussed and the gene-protein-substrate associations between the components of the list are presented. In addition, at http://www.ufrgs.br/icbs/hag we provide a network-based model of human antioxidant genes, which can be used as reference tool to access several database resources (e.g., RefSeq, Ensembl, HGNC and the NCBI Entrez database).
Topics: Antioxidants; Humans; Oxidation-Reduction; Peroxidase; Sulfhydryl Compounds; Superoxide Dismutase
PubMed: 19273363
DOI: 10.2741/3541 -
World Journal of Gastroenterology Jan 2023Ferroptosis is a newly discovered type of cell-regulated death. It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished... (Review)
Review
Ferroptosis is a newly discovered type of cell-regulated death. It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished from other forms of cell-regulated death by different morphology, biochemistry, and genetics. Recently, studies have shown that ferroptosis is associated with a variety of diseases, including liver, kidney and neurological diseases, as well as cancer. Ferroptosis has been shown to be associated with colorectal epithelial disorders, which can lead to cancerous changes in the gut. However, the potential role of ferroptosis in the occurrence and development of colorectal cancer (CRC) is still controversial. To elucidate the underlying mechanisms of ferroptosis in CRC, this article systematically reviews ferroptosis, and its cellular functions in CRC, for furthering the understanding of the pathogenesis of CRC to aid clinical treatment.
Topics: Humans; Ferroptosis; Cell Death; Iron; Kidney; Lipid Peroxidation; Colorectal Neoplasms
PubMed: 36688016
DOI: 10.3748/wjg.v29.i3.469 -
Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
The Cochrane Database of Systematic... Jun 2019Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.
OBJECTIVES
To assess the effects of ALC for the treatment of DPN.
SEARCH METHODS
On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods.
MAIN RESULTS
We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P = 0.17). The other two placebo-controlled studies reported no dropouts due to adverse events, and more pain, paraesthesia, and hyperaesthesias in the placebo group than the 3000 mg/day ALC group, but provided no numerical data. The overall certainty of adverse event evidence for the comparison of ALC versus placebo was low.The study comparing ALC with methylcobalamin reported that 34/117 participants (29.1%) experienced adverse events in the ALC group versus 33/115 (28.7%) in the methylcobalamin group (P = 0.95). Nine participants discontinued treatment due to adverse events (ALC: 4 participants, methylcobalamin: 5 participants), which were most commonly gastrointestinal symptoms. The certainty of the adverse event evidence for ALC versus methylcobalamin was low.Two studies were funded by the manufacturer of ALC and the other two studies had at least one co-author who was a consultant for an ALC manufacturer.
AUTHORS' CONCLUSIONS
We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.
Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12
PubMed: 31201734
DOI: 10.1002/14651858.CD011265.pub2 -
International Journal of Molecular... Apr 2021Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the...
Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against . Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.
Topics: Copper; Humans; Osteoblasts; Oxidation-Reduction; Porosity; Prostheses and Implants; Silver; Staphylococcal Infections; Staphylococcus aureus; Stem Cells; Titanium; Zinc
PubMed: 33917615
DOI: 10.3390/ijms22073800 -
Acta Ophthalmologica Feb 2022To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in dry eye disease (DED) compared with healthy subject. (Meta-Analysis)
Meta-Analysis
PURPOSE
To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in dry eye disease (DED) compared with healthy subject.
METHOD
The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 10 January 2021 for studies reporting oxidative and antioxidative stress markers in DED and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, conjunctival cells or biopsies), Sjögren's syndrome (SS) (patients with or without SS) and by geographical zones (Asia or Europe).
RESULTS
We included nine articles, for a total of 333 patients (628 eye samples) with DED and 165 healthy controls (451 eye samples). There is an overall increase in oxidative stress markers in DED compared with healthy controls (standard mean deviation = 2.39, 95% confidence interval 1.85-2.94), with a significant increase in lipid peroxide (1.90, 0.69-3.11), myeloperoxidase (2.17, 1.06-3.28), nitric oxide synthase 3 (2.52, 0.95-4.08), xanthine oxidase/oxidoreductase (2.41, 1.40-5.43), 4-hydroxy-2-nonenal (4HNE) (4.75, 1.67-7.84), malondialdehyde (3.00, 2.55-3.45) and reactive oxygen species (1.31, 0.94-1.68). Oxidative stress markers were higher in tears, conjunctival cells and conjunctival biopsies of DED than controls. Even if small number of studies were included for antioxidants, catalase seemed to be decreased in DED compared with healthy controls (-2.17, -3.00 to -1.34), with an increase of antioxidants in tears of DED patients without SS (1.13, 0.76-1.49).
CONCLUSION
Oxidative stress markers, and probably antioxidants, were dysregulated in DED, establishing a local oxidative environment in tears, conjunctival cells and tissues.
Topics: Biomarkers; Dry Eye Syndromes; Humans; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 33938134
DOI: 10.1111/aos.14892 -
Oxidative Medicine and Cellular... 2016Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue... (Review)
Review
Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD.
Topics: Animals; Antioxidants; Humans; Kidney; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Prognosis; Protein Carbonylation; Reactive Oxygen Species; Renal Insufficiency, Chronic
PubMed: 27563376
DOI: 10.1155/2016/8598253 -
World Journal of Microbiology &... Jul 2023Tellurium is a super-trace metalloid on Earth. Owing to its excellent physical and chemical properties, it is used in industries such as metallurgy and manufacturing,... (Review)
Review
Tellurium is a super-trace metalloid on Earth. Owing to its excellent physical and chemical properties, it is used in industries such as metallurgy and manufacturing, particularly of semiconductors and - more recently - solar panels. As the global demand for tellurium rises, environmental issues surrounding tellurium have recently aroused concern due to its high toxicity. The amount of tellurium released to the environment is increasing, and microorganisms play an important role in the biogeochemical cycling of environmental tellurium. This review focuses on novel developments on tellurium transformations driven by microbes and includes the following sections: (1) history and applications of tellurium; (2) toxicity of tellurium; (3) microbial detoxification mechanisms against soluble tellurium anions including uptake, efflux and methods of reduction, and reduced ability to cope with oxidation stress or repair damaged DNA; and (4) the characteristics and applications of tellurium nanoparticles (TeNPs) produced by microbes. This review raises the awareness of microorganisms in tellurium biogeochemical cycling and the growing applications for microbial tellurium nanoparticles.
Topics: Trace Elements; Tellurium; Nanoparticles
PubMed: 37507604
DOI: 10.1007/s11274-023-03704-2 -
The ISME Journal Jan 2024Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing... (Review)
Review
Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.
Topics: Methane; Oxidation-Reduction; Aerobiosis; Metabolic Networks and Pathways; Models, Biological
PubMed: 38861460
DOI: 10.1093/ismejo/wrae102 -
The Cochrane Database of Systematic... Oct 2006L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity, and acidifies the solution, thereby increasing calcium and phosphate solubility, and potentially improving bone mineralization.
OBJECTIVES
To determine the effects of supplementing parenteral nutrition with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes.
SEARCH STRATEGY
The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE (1966-December 2005), EMBASE (1974-December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and recent abstracts (until December 2005) from the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were searched.
SELECTION CRITERIA
All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed. Predetermined outcome variables included growth, nitrogen retention, mortality, morbidity secondary to oxidation injury, bone accretion, acidosis, liver disease, and cysteine levels.
DATA COLLECTION AND ANALYSIS
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD).
MAIN RESULTS
Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (< or = 1000 grams).
PRIMARY OUTCOMES
Growth was not significantly affected by cysteine supplementation (evaluated in one quasi-randomized trial) or by N-acetylcysteine supplementation (evaluated in one RCT). Nitrogen retention was significantly increased by cysteine supplementation (studied in four trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants).
SECONDARY OUTCOMES
Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH. No data were available on other outcomes.
AUTHORS' CONCLUSIONS
Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance.However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants. A large RCT would be required to assess whether routine prolonged cysteine supplementation of cysteine-free PN affects growth and short and long-term neonatal outcomes in very low birth weight infants.
Topics: Acetylcysteine; Cysteine; Cystine; Dietary Supplements; Humans; Infant, Newborn; Infant, Premature; Parenteral Nutrition; Randomized Controlled Trials as Topic
PubMed: 17054219
DOI: 10.1002/14651858.CD004869.pub2