-
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 -
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 -
Journal of Orthopaedic Surgery and... Mar 2024The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical... (Review)
Review
BACKGROUND
The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma.
OBJECTIVE
This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD).
METHODS
We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: "McCune-Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase", as well as other keywords were systematically searched. Papers published between January 2018 and May 2023 were selected for finding. Initial screening was performed by reading the titles and abstracts, and available literature was screened against the inclusion and exclusion criteria.
RESULTS
In this review, we systematically analyzed the cutting-edge advances in this disease, synthesized the findings, and discussed the differences. With regard to the complete mechanistic understanding of the pain condition in FD/MAS, in particular, we collated new findings on new pathways, neurotrophic factor receptors, purinergic receptors, interferon-stimulating factors, potassium channels, protein kinases, and corresponding hormonal modulation and their respective strengths and weaknesses.
CONCLUSION
This paper focuses on basic research to explore FD/MAS pain mechanisms. New nonneuronal and molecular mechanisms, mechanically loaded responsive neurons, and new targets for potential clinical interventions are future research directions, and a large number of animal experiments, tissue engineering techniques, and clinical trials are still needed to verify the effectiveness of the targets in the future.
Topics: Animals; Fibrous Dysplasia, Polyostotic; Fibrous Dysplasia of Bone; Pain; Bone Remodeling; China
PubMed: 38515135
DOI: 10.1186/s13018-024-04687-y -
Epilepsy & Behavior : E&B Jun 2024Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small... (Review)
Review
BACKGROUND
Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small non-coding RNAs known to play a crucial role in post-transcriptional regulation of gene expression.
METHODS
The present review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, employing a comprehensive search strategy to identify and extract data from published research articles. Keywords suchas epilepsy, micro RNA (micro RNAs, miRNA, miRNAs, miR), neurotransmitters (specific names), and neurotransmitter receptors (specific names) were used to construct the query.
RESULTS
A total of 724 articles were identified using the keywords epilepsy, microRNA along with select neurotransmitter and neurotransmitter receptor names. After exclusions, the final selection consisted of 17 studies, most of which centered on glutamate and gamma-aminobutyric acid (GABA) receptors. Singular studies also investigated miRNAs affecting cholinergic, purinergic, and glycine receptors.
CONCLUSION
This review offers a concise overview of the current knowledge on miRNA-mediated regulation of neurotransmitter receptors in epilepsy and highlights their potential for future clinical application.
PubMed: 38924965
DOI: 10.1016/j.yebeh.2024.109912 -
Platelets 2020Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its... (Meta-Analysis)
Meta-Analysis
Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its influence on platelet ADP-P2Y12 receptor inhibitors lack consistency. Thus, we conducted a systematic review and meta-analysis of already existing data/studies to further explore this issue. PubMed, Web of science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception to March 2018. Studies investigating the residual platelet reactivity categorized by smoking status and patients treated with platelet ADP-P2Y12 receptor inhibitors qualified the inclusion criteria. The primary outcome was P2Y12 reaction unit (PRU) value measured by VerifyNow P2Y12 assay, compared with different smoking status in ADP-P2Y12 receptor inhibitors treatment groups. Secondary outcome was post-treatment with 5 μmol/L ADP-inhibition of platelet aggregation (ADP-IPA) measured by light transmittance aggregometry (LTA). Of the 4954 citations retrieved, 12 studies involving 16 296 patients with acute coronary syndrome and/or stent deployment using platelet ADP-P2Y12 receptor inhibitors were included for meta-analysis. Pooled analysis revealed that PRU values of current smokers were 25.70 lower than nonsmokers (95% CI -38.81 to -12.60, = 0.0001), getting better effects of antiplatelet treatment. In the smoking extent subgroup analysis, patients smoking >10 cigarettes/day shown about 46.49 lower of PRU values than patients smoking <10 cigarettes/day ( < 0.00001). Racial subgroup analyses found that smokers had increased platelet inhibition in the Caucasian population. Further, pooled analysis of ADP-IPA values for 1658 patients from five studies showed a significantly lower residual platelet reactivity in current smokers compared to that in nonsmokers (MD = -4.19; 95% CI -6.55 to -1.83; = 0.0005). This systematic review and meta-analysis suggested that smokers have increased platelet inhibition and lower aggregation in response to clopidogrel than nonsmokers. These residual platelet reactivity observations may help to explain differential clinical outcomes in smokers vs. nonsmokers in large scale clinical trials.
Topics: Adult; Aged; Biomarkers; Blood Platelets; Clopidogrel; Humans; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Publication Bias; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Smoking
PubMed: 30744477
DOI: 10.1080/09537104.2019.1572878 -
Purinergic Signalling Dec 2023Transactivation of receptor tyrosine kinases (RTK) is a crosstalk mechanism exhibited by G-protein-coupled receptors (GPCR) to activate signaling pathways classically...
Transactivation of receptor tyrosine kinases (RTK) is a crosstalk mechanism exhibited by G-protein-coupled receptors (GPCR) to activate signaling pathways classically associated with growth factors. The discovery of RTK transactivation was a breakthrough in signal transduction that contributed to developing current concepts in intracellular signaling. RTK transactivation links GPCR signaling to important cellular processes, such as cell proliferation and differentiation, and explains the functional diversity of these receptors. Purinergic (P2Y and adenosine) receptors belong to class A of GPCR; in the present work, we systematically review the experimental evidence showing that purinergic receptors have the ability to transactivate RTK in multiple tissues and physiopathological conditions resulting in the modulation of cellular physiology. Of particular relevance, the crosstalk between purinergic receptors and epidermal growth factor receptor is a redundant pathway that participates in multiple pathophysiological processes. Specific and detailed knowledge of purinergic receptor-regulated pathways advances our understanding of the complexity of GPCR signal transduction and opens the way for pharmacologic intervention in the pathological context.
Topics: Receptor Protein-Tyrosine Kinases; Receptors, G-Protein-Coupled; Receptors, Purinergic P1; Signal Transduction; Transcriptional Activation; Tyrosine
PubMed: 36529846
DOI: 10.1007/s11302-022-09913-y -
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 Laryngoscope Jul 2020P2RX2 encoding P2X purinoreceptor 2 has been identified as the gene responsible for autosomal dominant deafness-41 (DFNA41) as well as mediating vulnerability to...
OBJECTIVES/HYPOTHESIS
P2RX2 encoding P2X purinoreceptor 2 has been identified as the gene responsible for autosomal dominant deafness-41 (DFNA41) as well as mediating vulnerability to noise-induced hearing loss (NIHL). The objective of this study was to investigate the audiological and molecular characteristics of P2RX2-related deafness, with emphasis on its role in NIHL by determining the audiological characteristics of a previously reported six-generation DFNA41 family with a 10-year follow-up. We have also summarized phenotype-genotype correlations of P2RX2-related deafness in human and mouse models.
STUDY DESIGN
We describe clinical longitudinal follow-up in the DFNA41 family with P2RX2 (p.Val60Leu) mutation and perform a systematic literature search in PubMed and poster presentations on meeting/conference websites to identify current insights into P2RX2-mediated NIHL.
METHODS
Clinical and physical examinations of the family members were performed, and audiograms were obtained to assess the hearing thresholds. Clinical follow-up features in this DFNA41 family are presented along with correlation analyses of phenotype-genotype in all reported families with P2RX2-related deafness.
RESULTS
Progressive hearing impairment was confirmed by history and by audiological follow-up testing in all the patients. The onset of hearing loss was between age 25 and 35 years. All affected subjects had bilateral sensorineural hearing loss involving all frequencies with some significant gender differences.
CONCLUSIONS
Our study and the review of the literature suggest that P2RX2 plays a crucial role in predisposition to noise-induced and age-related hearing loss. A better knowledge about the P2RX2-associated genetic variants can help in developing novel therapeutic strategies.
LEVEL OF EVIDENCE
2b Laryngoscope, 130:1657-1663, 2020.
Topics: Adult; Disease Progression; Female; Follow-Up Studies; Genotype; Hearing Loss, Sensorineural; Humans; Longitudinal Studies; Male; Middle Aged; Mutation; Pedigree; Phenotype; Receptors, Purinergic P2X2; Sex Factors
PubMed: 31593348
DOI: 10.1002/lary.28318 -
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