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Current Atherosclerosis Reports Nov 2014Oxidative stress due to an excess of reactive oxygen species (ROS) may play a role in the development and progression of cardiovascular disease (CVD).... (Review)
Review
Oxidative stress due to an excess of reactive oxygen species (ROS) may play a role in the development and progression of cardiovascular disease (CVD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a marker of oxidative DNA damage caused by ROS. This review aimed to assess the association between 8-OHdG and CVD by reviewing the literature. Studies in human subjects using either plasma or urine to determine 8-OHdG concentrations were surveyed. Eighteen relevant studies were found, of which 13 were case-control studies and five had a prospective design. Without exception, the case-control studies showed significant positive associations between 8-OHdG and CVD. In agreement, two prospective studies showed a significant association of 8-OHdG and heart failure. Furthermore, two prospective studies found a significant association between 8-OHdG and stroke, and finally, one prospective study showed a borderline significant (p = 0.08) association between coronary artery disease (CAD) patients developing a cardiac event and 8-OHdG concentrations. In conclusion, high levels of 8-OHdG in blood and urine are associated with atherosclerosis and heart failure, but further large prospective studies are needed to investigate 8-OHdG as a predictor for cardiovascular diseases.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Cardiovascular Diseases; Clinical Trials as Topic; DNA Damage; Deoxyguanosine; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 25252787
DOI: 10.1007/s11883-014-0452-y -
Frontiers in Immunology 2022Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases.
OBJECTIVES
The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group.
METHODS
We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups.
RESULTS
A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls.
CONCLUSION
Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.
Topics: Humans; Kynurenine; Kynurenic Acid; Tryptophan; Hydroxyindoleacetic Acid; Alzheimer Disease; Parkinson Disease; Huntington Disease; 3-Hydroxyanthranilic Acid; NAD; Adenosine; Niacinamide
PubMed: 36263032
DOI: 10.3389/fimmu.2022.997240 -
Journal of Cardiothoracic Surgery Dec 2022Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA... (Review)
Review
Despite the rise in morbidity and mortality associated with vascular diseases, the underlying pathophysiological molecular mechanisms are still unclear. RNA N6-methyladenosine modification, as the most common cellular mechanism of RNA regulation, participates in a variety of biological functions and plays an important role in epigenetics. A large amount of evidence shows that RNA N6-methyladenosine modifications play a key role in the morbidity caused by vascular diseases. Further research on the relationship between RNA N6-methyladenosine modifications and vascular diseases is necessary to understand disease mechanisms at the gene level and to provide new tools for diagnosis and treatment. In this study, we summarize the currently available data on RNA N6-methyladenosine modifications in vascular diseases, addressing four aspects: the cellular regulatory system of N6-methyladenosine methylation, N6-methyladenosine modifications in risk factors for vascular disease, N6-methyladenosine modifications in vascular diseases, and techniques for the detection of N6-methyladenosine-methylated RNA.
Topics: Humans; Methylation; RNA; Adenosine; Vascular Diseases
PubMed: 36536469
DOI: 10.1186/s13019-022-02077-1 -
Multiple Sclerosis and Related Disorders Mar 2023The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low- to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.
METHODS
We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.
RESULTS
Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.
DISCUSSION
EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
Topics: Adult; Humans; Multiple Sclerosis; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Cladribine
PubMed: 36848839
DOI: 10.1016/j.msard.2023.104581 -
Clinical Pharmacokinetics May 2023Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in... (Review)
Review
Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5-15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associated with increased hospital admission, length, costs, and poor prognosis. Although the effects of other antithrombotic therapies, such as direct oral anticoagulants, can be reversed by approved specific agents, there are no approved reversal agents for any antiplatelet drugs. The fact that many antiplatelet agents, such as aspirin and thienopyridines (i.e., clopidogrel and prasugrel), bind irreversibly to their targets represents a challenge for the development of a drug-specific reversal agent. In contrast, ticagrelor is a non-thienopyridine with a plasma half-life of 7-9 h that reversely binds the P2Y receptor producing potent signaling blockage. In 2015, bentracimab (also known as PB2452 or MEDI2452), a neutralizing monoclonal antibody fragment that binds free plasma ticagrelor and its major active metabolite, was identified. This systematic overview provides a comprehensive summary of the drug development program of bentracimab, focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.
Topics: Humans; Acute Coronary Syndrome; Antibodies, Monoclonal; Clopidogrel; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor
PubMed: 37118383
DOI: 10.1007/s40262-023-01245-3 -
Molecules (Basel, Switzerland) Sep 2021We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models.... (Review)
Review
We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.
Topics: Animals; Antineoplastic Agents; Brain Diseases; Deoxyadenosines; Humans; Inflammation; Metabolic Diseases; Neoplasms; Signal Transduction
PubMed: 34641429
DOI: 10.3390/molecules26195886 -
Biomedical Papers of the Medical... Mar 2024Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation... (Meta-Analysis)
Meta-Analysis Review
Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.
Topics: Child; Animals; Humans; Aged; 8-Hydroxy-2'-Deoxyguanosine; Creatinine; DNA Damage; Comet Assay; Hypertension
PubMed: 37916467
DOI: 10.5507/bp.2023.044 -
Heart, Lung & Circulation May 2018Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We performed a systematic review and meta-analysis to assess the impact of adenosine administration in patients undergoing PVI for AF.
METHODS
Meta-analysis of 22 studies was performed to assess the rates of freedom from AF in 1) patients with dormant PV conduction versus patients without dormant PV conduction, and 2) patients given routine adenosine post PVI versus patients not given adenosine. Relative-risks (RR) were calculated using random effects modelling.
RESULTS
In 18 studies, 3038 patients received adenosine and freedom from AF in those patients with dormant PV reconnection was significantly lower (62.9%) compared to patients without PV reconnection (67.2%) (RR 0.87; 95% CI: 0.78-0.98). In seven studies with 3049 patients, the freedom from AF was significantly higher in patients who received adenosine (67%) versus those patients who did not receive adenosine (63%) (RR: 1.11; 95% CI: 1.01-1.22).
CONCLUSIONS
The present study showed clear benefits of adenosine testing for freedom from AF recurrence. Adenosine-guided dormant conduction is associated with higher AF recurrence despite further ablation. Future studies should investigate the optimal methodology, including dosage and waiting time between PVI and adenosine administration.
Topics: Adenosine; Atrial Fibrillation; Catheter Ablation; Heart Conduction System; Heart Rate; Humans; Postoperative Period; Vasodilator Agents
PubMed: 28655535
DOI: 10.1016/j.hlc.2017.04.020 -
Medicine Dec 2023A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic coronary syndromes patients.
METHODS
Electronic databases (Pubmed, Embase and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different antiplatelet or anticoagulation drugs (aspirin, aspirin + clopidogrel, aspirin + clopidogrel + cilostazol, clopidogrel/prasugrel + aspirin, aspirin + rivaoxaban 2.5 mg, aspirin + ticagrelor 60 mg, aspirin + ticagrelor 90 mg, clopidogrel or rivroxaban 5 mg) versus placebo for treatment chronic coronary syndromes patients. Outcomes included major adverse cardiovascular events, all cause death, major bleeding and myocardial infarction. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking probabilities.
RESULTS
Ten randomized controlled trials met criteria for inclusion and finally included in this NMA. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to primary endpoint of major adverse cardiovascular events. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to all cause death. Clopidogrel/prasugrel + aspirin (OR = 3.8, 95% credible intervals [CrI]: 1.3-12.0, P < .05) and aspirin + rivaroxaban 2.5 mg (OR = 3.1, 95%CrI: 1.1-9.5, P < .05) was associated with an increase of the major bleeding. Compared with aspirin alone, aspirin + clopidogrel (OR = 0.42, 95%CrI: 0.22-0.76, P < .05) and aspirin + ticagrelor 90 mg (OR = 0.42, 95%CrI: 0.17-0.95, P < .05) was associated with a decrease of the myocardial infarction.
CONCLUSIONS
Myocardial infarction was significantly lower when adding clopidogrel or ticagrelor 90 mg to aspirin than those in the aspirin alone group. However, clopidogrel/prasugrel and rivaroxaban 2.5 mg was associated with an increase of the major bleeding than aspirin alone.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Ticagrelor; Prasugrel Hydrochloride; Rivaroxaban; Network Meta-Analysis; Bayes Theorem; Fibrinolytic Agents; Aspirin; Myocardial Infarction; Hemorrhage; Anticoagulants; Acute Coronary Syndrome; Treatment Outcome
PubMed: 38050293
DOI: 10.1097/MD.0000000000036429 -
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