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Cephalalgia : An International Journal... Jul 2022To systematically review clinical studies investigating the involvement of adenosine and its receptors in migraine pathophysiology.
OBJECTIVE
To systematically review clinical studies investigating the involvement of adenosine and its receptors in migraine pathophysiology.
BACKGROUND
Adenosine is a purinergic signaling molecule, clinically used in cardiac imaging during stress tests. Headache is a frequent adverse event after intravenous adenosine administration. Migraine headache relief is reported after intake of adenosine receptor antagonist, caffeine. These findings suggest a possible involvement of adenosine signaling in migraine pathophysiology and its potential as a drug target.
METHODS
A search through PubMed and EMBASE was undertaken for clinical studies investigating the role of adenosine and its receptors in migraine, published until September 2021.
RESULTS
A total of 2510 studies were screened by title and abstract. Of these, seven clinical studies were included. The main findings were that adenosine infusion induced headache, and plasma adenosine levels were elevated during ictal compared to interictal periods in migraine patients.
CONCLUSION
The present systematic review emphasizes a potentially important role of adenosine signaling in migraine pathogenesis. Further randomized and placebo-controlled clinical investigations applying adenosine receptors modulators in migraine patients are needed to further understand the adenosine involvement in migraine.
Topics: Adenosine; Headache; Humans; Migraine Disorders; Signal Transduction
PubMed: 35301855
DOI: 10.1177/03331024221077665 -
The Indian Journal of Tuberculosis Jan 2022Tuberculosis (TB) is one of the most important infectious diseases and is accounted for as the second most common cause of death due to infectious agents after HIV. It... (Meta-Analysis)
Meta-Analysis
Tuberculosis (TB) is one of the most important infectious diseases and is accounted for as the second most common cause of death due to infectious agents after HIV. It is estimated that a quarter of the world's population is infected with Mycobacterium tuberculosis (Mtb), and 5-10% of whom will be infected with active TB. Introducing a biomarker to predict TB can help control the disease and reduces the burden of mortality from this infectious disease. P2X7/P2X7R is one of the most important axes of the innate immune system, which its activity increases the clearance of the residual bacteria in macrophages. Numerous studies have shown the association between rs3751143 polymorphism and susceptibility to TB. The present study aimed to evaluate the diagnostic value of this polymorphism in predicting TB. In the current quantitative analysis, we studied the data from twenty relevant case-control studies, consisting of 10,544 volunteers. We found that, although rs3751143 polymorphism causes susceptibility to TB, but based on statistical analysis, it cannot be considered as a reliable biomarker for the diagnosis of TB.
Topics: Biomarkers; Humans; Mycobacterium tuberculosis; Polymorphism, Genetic; Receptors, Purinergic P2X7; Reproducibility of Results; Tuberculosis
PubMed: 35074157
DOI: 10.1016/j.ijtb.2021.04.004 -
Frontiers in Pharmacology 2021The role of purinergic P2X7 receptor (P2X7R) is of interest due to its involvement in inflammation and mediating immune cell responses. P2X7R is particularly implicated... (Review)
Review
The role of purinergic P2X7 receptor (P2X7R) is of interest due to its involvement in inflammation and mediating immune cell responses. P2X7R is particularly implicated in the development of inflammatory bowel disease (IBD). However, the extent of the actions of P2X7R in the gastrointestinal (GI) system under physiological and pathophysiological conditions remains to be elucidated. This systematic review aimed to identify, summarize and evaluate the evidence for a critical role of P2X7R in the GI system. We searched PubMed, Embase and Scopus with search terms pertained to P2X7R in the GI system in disease or physiological state, including "P2X7 or P2X7 receptor or purinergic signaling" in combination with any of the terms "intestine or colon or gut or gastrointestinal," "pathology or inflammation or disease or disorder," and "physiology or expression." Titles and abstracts were screened for potentially eligible full texts, and animal and human studies published in English were included in this study. Data were extracted from papers meeting inclusion criteria. Meta-analysis was not feasible given the study diversity. There were 48 papers included in this review. We identified 14 experimental colitis models, three sepsis models and one ischemia-reperfusion injury model. Among them, 11 studies examined P2X7R in GI infections, six studies on immune cell regulation, four studies on GI inflammation, two studies on GI malignancies, three studies involving intestinal injury due to various causes, two studies on ATP-activated P2X7R in the GI system and two studies on metabolic regulation. Evidence supports P2X7R mediating inflammation and immune cell responses in GI inflammation, infections and injury due to IBD and other challenges to the intestinal wall. P2X7R inhibition by gene knockout or by application of P2X7R antagonists can reduce tissue damage by suppressing inflammation. P2X7R is also implicated in GI malignancies and glucose and lipid homeostasis. P2X7R blockade, however, did not always lead to beneficial outcomes in the various pathological models of study.
PubMed: 34987401
DOI: 10.3389/fphar.2021.786579 -
JAMA Network Open Nov 2021The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved... (Meta-Analysis)
Meta-Analysis
Assessment of Pretreatment With Oral P2Y12 Inhibitors and Cardiovascular and Bleeding Outcomes in Patients With Non-ST Elevation Acute Coronary Syndromes: A Systematic Review and Meta-analysis.
IMPORTANCE
The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved cardiovascular outcomes is unclear.
OBJECTIVE
To assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS.
DATA SOURCES
On March 20, 2021, PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for Controlled Trials were searched from database inception.
STUDY SELECTION
Randomized clinical trials of patients with NSTEACS randomized to either oral P2Y12 inhibitor pretreatment (defined as prior to angiography) or no pretreatment (defined as following angiography, once coronary anatomy was known) among patients undergoing an invasive strategy.
DATA EXTRACTION AND SYNTHESIS
This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data on publication year, sample size, clinical characteristics, revascularization strategy, P2Y12 inhibitor type and dosage, time from pretreatment to angiography, and end point data were independently extracted by 2 authors. A random-effects model was used, including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site.
MAIN OUTCOMES AND MEASURES
The primary end point was 30-day major adverse cardiac events (MACEs). Secondary end points were 30-day myocardial infarction (MI) and cardiovascular death. The primary safety end point was 30-day major bleeding (defined according to individual studies).
RESULTS
A total of 7 trials randomizing 13 226 patients to either pretreatment (6603 patients) or no pretreatment (6623 patients) were included. The mean age of patients was 64 years and 3598 (27.2%) were female individuals. Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention. Pretreatment was not associated with a reduction in 30-day MACE (odds ratio [OR], 0.95; 95% CI, 0.78-1.15; I2 = 28%), 30-day MI (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%). The risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51; 95% CI, 1.16-1.97; I2 = 41%). The number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients.
CONCLUSIONS AND RELEVANCE
In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study.
Topics: Acute Coronary Syndrome; Aged; Female; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Preoperative Care; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Treatment Outcome
PubMed: 34797371
DOI: 10.1001/jamanetworkopen.2021.34322 -
Archives of Biochemistry and Biophysics Oct 2021Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly...
Mechanical environments were associated with alterations in bone metabolism. Ion channels present on bone cells are indispensable for bone metabolism and can be directly or indirectly activated by mechanical stimulation. This review aimed to discuss the literature reporting the mechanical regulatory effects of ion channels on bone cells and bone tissue. An electronic search was conducted in PubMed, Embase and Web of Science. Studies about mechanically induced alteration of bone cells and bone tissue by ion channels were included. Ion channels including TRP family channels, Ca release-activated Ca channels (CRACs), Piezo1/2 channels, purinergic receptors, NMDA receptors, voltage-sensitive calcium channels (VSCCs), TREK2 potassium channels, calcium- and voltage-dependent big conductance potassium (BK) channels, small conductance, calcium-activated potassium (SK) channels and epithelial sodium channels (ENaCs) present on bone cells and bone tissue participate in the mechanical regulation of bone development in addition to contributing to direct or indirect mechanotransduction such as altered membrane potential and ionic flux. Physiological (beneficial) mechanical stimulation could induce the anabolism of bone cells and bone tissue through ion channels, but abnormal (harmful) mechanical stimulation could also induce the catabolism of bone cells and bone tissue through ion channels. Functional expression of ion channels is vital for the mechanotransduction of bone cells. Mechanical activation (opening) of ion channels triggers ion influx and induces the activation of intracellular modulators that can influence bone metabolism. Therefore, mechanosensitive ion channels provide new insights into therapeutic targets for the treatment of bone-related diseases such as osteopenia and aseptic implant loosening.
Topics: Animals; Bone and Bones; Cell Line; Humans; Ion Channels; Mechanotransduction, Cellular; Receptors, Purinergic
PubMed: 34461086
DOI: 10.1016/j.abb.2021.109020 -
Biomedicines Jul 2021Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.
PubMed: 34440069
DOI: 10.3390/biomedicines9080865 -
Bioscience Reports Feb 2021Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer.
MATERIALS AND METHODS
The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel-Haenszel) or random-effects (DerSimonian-Laird) models were selected to summarise the collective effects.
RESULTS
Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models.
CONCLUSIONS
Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.
Topics: Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Genetic; Receptors, Purinergic P2X7
PubMed: 33501930
DOI: 10.1042/BSR20193877 -
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 -
Clinical Cardiology Mar 2020The optimal antiplatelet therapy after percutaneous coronary intervention (PCI) remains to be elucidated. Monotherapy with a P2Y12 inhibitor may be inferior to dual... (Meta-Analysis)
Meta-Analysis
The optimal antiplatelet therapy after percutaneous coronary intervention (PCI) remains to be elucidated. Monotherapy with a P2Y12 inhibitor may be inferior to dual antiplatelet therapy in patients after PCI. PubMed, EMBASE (by Ovidsp), Web of Science, and The Cochrane Library were searched from database inception to 2 October 2019. The composite of cardiovascular outcomes, all-cause mortality, myocardial infarction (MI), stroke, stent thrombosis, and major bleeding were evaluated. Pooled outcomes were presented as relative risk (RR) and 95% confidence intervals (CIs). A total of four trials randomizing 29 089 participants were included. Compared with the dual antiplatelet therapy group (n = 14 559), the P2Y12 inhibitor monotherapy group (n = 14 530) significantly decreased the incidence of bleeding events (2.0% vs 3.1%; RR: 0.60; 95% CI: 0.43-0.84; P = .005). There were no significant differences in all-cause mortality (1.3% vs 1.5%; RR: 0.87; 95% CI, 0.71-1.06; P = .16), myocardial infarction (2.1% vs 1.9%; RR, 1.06; 95% CI, 0.90-1.25; P = .46), stroke (0.6% vs 0.5%; RR, 1.18; 95% CI, 0.67-2.07; P = .57), or stent thrombosis (0.5% vs 0.4%; RR, 1.14; 95% CI, 0.81-1.61; P = .44) between the two groups. P2Y12 inhibitor monotherapy did not show any significant difference in the adverse cardiac and cerebrovascular events, but markedly decreased the risk of bleeding among patients after PCI vs dual antiplatelet therapy. However, it still needs to be further confirmed due to limited data.
Topics: Aged; Blood Platelets; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Stents; Stroke; Time Factors; Treatment Outcome
PubMed: 31777973
DOI: 10.1002/clc.23305 -
Journal of Thrombosis and Thrombolysis Jan 2020The optimal duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is subject to debate. A short-duration DAPT (one month to three... (Comparative Study)
Comparative Study Meta-Analysis
Short-term dual antiplatelet therapy (DAPT) followed by P2Y12 monotherapy versus traditional DAPT in patients undergoing percutaneous coronary intervention: meta-analysis and viewpoint.
The optimal duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is subject to debate. A short-duration DAPT (one month to three months) followed by P2Y monotherapy instead of standard 6 to 12 months DAPT followed by aspirin monotherapy after PCI has been suggested. We meta-analyzed studies comparing short-term (≤ 3 months) DAPT followed by P2Y monotherapy versus standard DAPT in patients after PCI. In total, 2304 studies were screened at title and abstract level. The primary endpoint was major bleeding. Secondary endpoints included myocardial infarction, stent thrombosis, stroke, and all-cause mortality. Study level data were analyzed. Heterogeneity was assessed using the I statistic. Risk rates (RR) were calculated using a random-effects model (DerSimonian and Laird) for clinical outcomes for each individual study and consecutive pooling. In total, 21970 patients from three studies were analyzed. Between P2Y inhibitor monotherapy versus DAPT, there were similar rates of major bleeding (RR 0.67 95%CI 0.34-1.32; p = 0.25; I 75%), mortality (RR 0.92 95%CI 0.78-1.09; p = 0.33; I 0%) and stroke (RR 0.97 95%CI 0.52 - 0.18; p = 0.92; I 57%). Endpoints assessing thrombotic events showed no statistically significant difference including myocardial infarction (RR 0.99 95%CI 0.85-1.15; p = 0.86; I 0%) and stent thrombosis (RR 1.03 95%CI 0.74-1.44; p = 0.87; I 0%). The experimental treatment with P2Y monotherapy after very short-term DAPT was not superior to standard DAPT. Our meta-analysis adds insight that DAPT might be safely shortened in selected patient strategies. However, DAPT remains the gold standard for antithrombotic treatment after PCI.
Topics: Aspirin; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12
PubMed: 31686298
DOI: 10.1007/s11239-019-01985-9