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Epigenetics Aug 2021N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate...
N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate network architecture by which m6A epitranscriptome impacts on immune response and function. However, it was only until recently that the mechanisms underlying the involvement of m6A modification in immune system were uncovered. Here, we systematically review the m6A involvement in the regulation of innate and adaptive immune cells. Further, the interplay between m6A modification and anti-inflammatory, anti-viral and anti-tumour immunity is also comprehensively summarized. Finally, we focus on the future prospects of m6A modification in immune modulation. A better understanding of the crosstalk between m6A modification and immune system is of great significance to reveal new pathogenic pathways and to develop promising therapeutic targets of diseases.
Topics: Adenosine; DNA Methylation; Immune System; Logic
PubMed: 33070685
DOI: 10.1080/15592294.2020.1827722 -
BMC Cardiovascular Disorders Oct 2020This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS).
METHODS
Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR).
RESULTS
Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = - 32.26; 95% CI: - 56.48 to - 8.76; P < 0.01; VASP-PRI: WMD = - 9.61; 95% CI: - 14.63 to - 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12-0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08-1.81; P = 0.01).
CONCLUSIONS
Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.
Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cell Adhesion Molecules; Female; Humans; Male; Microfilament Proteins; Middle Aged; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome
PubMed: 33004000
DOI: 10.1186/s12872-020-01603-0 -
The Cochrane Database of Systematic... Jul 2020Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that can develop in pregnancy. It occurs when there is a build-up of bile acids in the maternal blood. It has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been largely empiric. As ICP is an uncommon condition (incidence less than 2% a year), many trials have been small. Synthesis, including recent larger trials, will provide more evidence to guide clinical practice. This review is an update of a review first published in 2001 and last updated in 2013.
OBJECTIVES
To assess the effects of pharmacological interventions to treat women with intrahepatic cholestasis of pregnancy, on maternal, fetal and neonatal outcomes.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 December 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials, including cluster-randomised trials and trials published in abstract form only, that compared any drug with placebo or no treatment, or two drug intervention strategies, for women with a clinical diagnosis of intrahepatic cholestasis of pregnancy.
DATA COLLECTION AND ANALYSIS
The review authors independently assessed trials for eligibility and risks of bias. We independently extracted data and checked these for accuracy. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 26 trials involving 2007 women. They were mostly at unclear to high risk of bias. They assessed nine different pharmacological interventions, resulting in 14 different comparisons. We judged two placebo-controlled trials of ursodeoxycholic acid (UDCA) in 715 women to be at low risk of bias. The ten different pharmacological interventions were: agents believed to detoxify bile acids (UCDA) and S-adenosylmethionine (SAMe); agents used to bind bile acids in the intestine (activated charcoal, guar gum, cholestyramine); Chinese herbal medicines (yinchenghao decoction (YCHD), salvia, Yiganling and Danxioling pill (DXLP)), and agents aimed to reduce bile acid production (dexamethasone) Compared with placebo, UDCA probably results in a small improvement in pruritus score measured on a 100 mm visual analogue scale (VAS) (mean difference (MD) -7.64 points, 95% confidence interval (CI) -9.69 to -5.60 points; 2 trials, 715 women; GRADE moderate certainty), where a score of zero indicates no itch and a score of 100 indicates severe itching. The evidence for fetal distress and stillbirth were uncertain, due to serious limitations in study design and imprecision (risk ratio (RR) 0.70, 95% CI 0.35 to 1.40; 6 trials, 944 women; RR 0.33, 95% CI 0.08 to 1.37; 6 trials, 955 women; GRADE very low certainty). We found very few differences for the other comparisons included in this review. There is insufficient evidence to indicate if SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with intrahepatic cholestasis of pregnancy.
AUTHORS' CONCLUSIONS
When compared with placebo, UDCA administered to women with ICP probably shows a reduction in pruritus. However the size of the effect is small and for most pregnant women and clinicians, the reduction may fall below the minimum clinically worthwhile effect. The evidence was unclear for other adverse fetal outcomes, due to very low-certainty evidence. There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, YCHD, DXLP, Salvia, Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy. There are no trials of the efficacy of topical emollients. Further high-quality trials of other interventions are needed in order to identify effective treatments for maternal itching and preventing adverse perinatal outcomes. It would also be helpful to identify those women who are mostly likely to respond to UDCA (for example, whether bile acid concentrations affect how women with ICP respond to treatment with UDCA).
Topics: Charcoal; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Dexamethasone; Drugs, Chinese Herbal; Female; Fetal Distress; Galactans; Glucocorticoids; Humans; Mannans; Plant Gums; Pregnancy; Pregnancy Complications; Pruritus; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Stillbirth; Ursodeoxycholic Acid
PubMed: 32716060
DOI: 10.1002/14651858.CD000493.pub3 -
International Journal of Molecular... May 2020Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant... (Meta-Analysis)
Meta-Analysis
Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Female; Humans; Male; Meta-Analysis as Topic; Oxidative Stress; Smoking
PubMed: 32466448
DOI: 10.3390/ijms21113743 -
British Journal of Clinical Pharmacology Aug 2020We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of clopidogrel versus prasugrel and ticagrelor for coronary artery disease treatment in patients with CYP2C19 LoF alleles: a systemic review and meta-analysis.
AIM
We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19 reduced-metabolizers.
METHODS
PubMed, Cochrane and Web of Science were systematically searched for randomized controlled trials or cohort studies up to January 2020. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stent thrombosis and stroke. The secondary endpoint was bleeding. Pooled effects were measured by relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated with Egger's regression test and adjusted by trim and fill method.
RESULTS
Twelve studies comprising 5829 CV patients with CYP2C19 loss-of-function alleles were included. Patients who received ticagrelor or prasugrel showed a lower risk of MACE than those who received clopidogrel (RR 0.524; 95% CI: 0.375, 0.731). The former also had lower risks of CV death (RR 0.409; 95% CI: 0.177, 0.946), all-cause death (RR 0.441; 95% CI: 0.263, 0.739), MI (RR 0.554; 95% CI: 0.414, 0.741) and stent thrombosis (RR 0.587; 95% CI: 0.348, 0.988) than the latter patient group. The risk of stroke was not significantly different between patients receiving the alternatives and those receiving clopidogrel (RR 0.605; 95% CI: 0.257, 1.425). Major and minor bleeding risk was not significantly different between patients treated with alternatives and clopidogrel (RR 1.019; 95% CI: 0.827, 1.260 and RR 1.235; 95% CI: 0.581, 2.628, respectively).
CONCLUSION
CYP2C19 reduced-metabolizers can expect better clinical outcome on using prasugrel or ticagrelor rather than clopidogrel.
Topics: Acute Coronary Syndrome; Alleles; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome
PubMed: 32320492
DOI: 10.1111/bcp.14317 -
British Journal of Haematology Jun 2020Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete...
Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.
Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).
Topics: Adult; Age of Onset; Aged, 80 and over; Antimetabolites; Cladribine; Dose-Response Relationship, Drug; Female; France; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Proportional Hazards Models; Remission Induction; Retrospective Studies; Sepsis; Virus Diseases
PubMed: 32191819
DOI: 10.1111/bjh.16449 -
BMC Cardiovascular Disorders Mar 2020Ticagrelor and prasugrel are two third-generation oral P2Y inhibitors which are more commonly used in clinical practice. However, dyspnea has been consecutively reported... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ticagrelor and prasugrel are two third-generation oral P2Y inhibitors which are more commonly used in clinical practice. However, dyspnea has been consecutively reported in patients using third-generation oral P2Y inhibitors. This study aims to compare the risk of dyspnea in patients treated with third-generation P2Y inhibitors compared with clopidogrel.
METHODS
We systematically searched the PubMed, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov and Web of Science for randomized control trials (RCTs) comparing ticagrelor or prasugrel with clopidogrel until July 2019. The primary outcome was the incidence of dyspnea. The risk ratios (RR) and 95% confidence intervals (CI) were estimated using meta-analysis.
RESULTS
We included 25 RCTs involving 63,484 patients in this meta-analysis, including 21 studies on ticagrelor and 4 studies on prasugrel. Compared to the clopidogrel group, third-generation oral P2Y inhibitors were associated with an increased risk of dyspnea compared with clopidogrel (RR 2.15, 95% CI 1.59-2.92), which was consistent in the analysis of ticagrelor (RR 2.65, 95% CI 1.87-3.76). However, the adverse effect was not found among patients receiving prasugrel therapy (RR 1.03, 95% CI 0.86-1.22). The increased dyspnea risk of ticagrelor was consistent in subgroups with different follow-up durations (≤ 1 month RR 1.87, 95% CI 1.56-2.24; 1-6 months RR 4.19, 95% CI 1.99-8.86; > 6 months 2.45, 95% CI 1.13-5.34).
CONCLUSIONS
Ticagrelor has a higher risk of dyspnea than clopidogrel, which was not observed in patients using prasugrel.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Clopidogrel; Dyspnea; Female; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Ticagrelor; Young Adult
PubMed: 32183711
DOI: 10.1186/s12872-020-01419-y -
BMC Cardiovascular Disorders Mar 2020For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y... (Meta-Analysis)
Meta-Analysis
Prasugrel or ticagrelor relative to clopidogrel in triple-antiplatelet treatment combined with glycoprotein IIb/IIIa inhibitor for patients with STEMI undergoing PCI: a meta-analysis.
BACKGROUND
For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y antagonists, including prasugrel or ticagrelor, has not been established relative to that of the clopidogrel-based triple-antiplatelet treatments (TAPTs; in combination with glycoprotein IIb/IIIa inhibitor). The present meta-analysis evaluated the efficacy and safety of prasugrel- or ticagrelor-based TAPTs relative to that of clopidogrel TAPTs in patients with STEMI undergoing PCI.
METHODS
The databases PubMed, Embase, and Cochrane's Library were systematically searched for relevant randomized controlled trials concerning prasugrel or ticagrelor (test) relative to clopidogrel (control). Depending on heterogeneity, studies were pooled with a random effects or a fixed effects model. Outcomes of blood flow after PCI were evaluated, including TIMI (thrombolysis in myocardial infarction), bleeding events, and major adverse cardiovascular events (MACEs).
RESULTS
Seven studies comprising 11,874 patients conformed to the inclusion criteria. The pooled results with the fixed effects model indicated that after PCI patients in the prasugrel or ticagrelor groups were as likely as those treated with clopidogrel to achieve TIMI grade 3 flow or experience bleeding events. However, compared with the control, the test groups had significantly less risk of MACE (OR: 0.81, 95% CI: 0.70-0.94, P = 0.004), especially at the 1-year follow-up (OR: 0.79, 95% CI: 0.66-0.95, P = 0.01).
CONCLUSIONS
A prasugrel- or ticagrelor-based TAPT may reduce the rate of MACEs, without increasing bleeding in STEMI patients undergoing PCI. However, due to the limited RCT studies and variations in study weight, results of this meta-analysis should be confirmed in a large RCT with adequate sample size and follow-up duration.
Topics: Aged; Aged, 80 and over; Clopidogrel; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome
PubMed: 32164560
DOI: 10.1186/s12872-020-01403-6 -
Journal of the American Heart... Feb 2020Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of High Potent P2Y Inhibitors Prasugrel and Ticagrelor in Patients With Coronary Heart Disease Treated With Dual Antiplatelet Therapy: A Sex-Specific Systematic Review and Meta-Analysis.
Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex-specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow-up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80-1.00; men: RR, 0.84 [95% CI, 0.79-0.91) ( for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high-potency dual antiplatelet therapy (RR, 1.18 [95% CI, 0.98-1.41] versus RR, 1.03 [95% CI, 0.93-1.14]) ( for interaction=0.20). Conclusions The small and statistically insignificant difference in efficacy and safety estimates of high-potency dual antiplatelet therapy between women and men following percutaneous coronary intervention/acute coronary syndrome do not justify differential dual antiplatelet therapy treatment for both sexes.
Topics: Aspirin; Clopidogrel; Coronary Disease; Dual Anti-Platelet Therapy; Female; Humans; Male; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Sex Factors; Ticagrelor; Treatment Outcome
PubMed: 32063118
DOI: 10.1161/JAHA.119.014457 -
BMC Cancer Oct 2019High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear.
METHODS
A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value.
RESULTS
A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses.
CONCLUSIONS
This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; DNA Damage; Disease-Free Survival; Humans; Neoplasms; Oxidative Stress; Prognosis; Proportional Hazards Models; Reactive Oxygen Species
PubMed: 31651287
DOI: 10.1186/s12885-019-6189-9