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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 -
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 -
Pulmonary Pharmacology & Therapeutics Dec 2023Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important... (Meta-Analysis)
Meta-Analysis Review
Safety and efficacy of P2X3 receptor antagonist for the treatment of refractory or unexplained chronic cough: A systematic review and meta-analysis of 11 randomized controlled trials.
BACKGROUND AND OBJECTIVES
Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important part in nerve fiber sensitization and pathological pain pathways. We conducted this systematic review and meta-analysis to determine the long-term safety and efficacy of P2X3 receptor antagonist drugs in chronic cough.
METHODS
We systematically searched PubMed, Scopus, Web of Science, and Embase to identify all relevant published studies through January 15, 2023 that assessed P2X3 antagonists in chronic cough. The protocol was registered in the PROSPERO database with ID: CRD42023422408. Efficacy outcomes were awake (daytime) cough frequency, night cough frequency, 24-h cough frequency, Cough Severity Diary, and total Leicester Cough Questionnaire score. We used the random-effect model to pool the data using RStudio and CMA software.
RESULTS
A total of 11 randomized controlled trials comprising 1350 patients receiving a p2x3 antagonist compared to the placebo group were included in this meta-analysis. A significant decrease in 24-h cough frequency (MD = -4.99, 95% CI [-7.15 to -2.82], P < 0.01), awake (daytime) cough frequency (MD = -7.18, 95% CI [-9.98 to 4.37], P < 0.01), and total Leicester Cough Questionnaire score (MD = 1.74, 95% CI [1.02 to 2.46], P < 0.01) exhibited between the P2X3 antagonist and placebo groups. The frequency of the night cough showed an insignificant difference between the two groups. According to the safety, drug-related adverse events, dysgeusia, hypogeusia, and ageusia significantly increased between the P2X3 antagonist and placebo groups.
CONCLUSION
P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia.
Topics: Humans; Purinergic P2X Receptor Antagonists; Ageusia; Dysgeusia; Chronic Disease; Randomized Controlled Trials as Topic; Cough
PubMed: 37678663
DOI: 10.1016/j.pupt.2023.102252 -
Thrombosis and Haemostasis May 2024The value of guided therapy (GT) with anti-P2Y12 drugs in percutaneous coronary intervention (PCI) is unclear. Meta-analyses lumped together randomized controlled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The value of guided therapy (GT) with anti-P2Y12 drugs in percutaneous coronary intervention (PCI) is unclear. Meta-analyses lumped together randomized controlled trials (RCTs) with heterogeneous designs, comparing either genotype-GT or platelet function test (PFT)-GT with unguided therapy. Some meta-analysis also included RCTs that did not explore GT, but included the effects of switching patients with high on-treatment platelet reactivity (HTPR) to alternative therapies (HTPR-Therapy). We performed three distinct systematic reviews/meta-analyses, each exploring only RCTs with homogeneous design.
METHODS
MEDLINE, Embase, and Central databases were searched for RCTs testing genotype-GT, PFT-GT, or HTPR-Therapy in PCI-treated patients, through October 1, 2022. Two reviewers extracted the data. Risk ratios (RRs) (95% confidence intervals) were calculated. Primary outcomes were major bleedings (MBs) and major adverse cardiovascular events (MACE).
RESULTS
In seven genotype-GT RCTs, RRs were: MB, 1.06 (0.73-1.54; = 0.76); MACE, 0.65 (0.47-0.91; = 0.01), but significant risk reduction was observed in RCTs performed in China (0.30, 0.16-0.54; < 0.0001) and not elsewhere (0.75, 0.48-1.18; = 0.21). In six PFT-GT RCTs, RRs were: MB, 0.91 (0.64-1.28, = 0.58); MACE, 0.82 (0.56-1.19; = 0.30): 0.62 (0.42-0.93; = 0.02) in China, 1.08 (0.82-1.41; = 0.53) elsewhere. In eight HTPR-Therapy RCTs, RRs were: MB, 0.71 (0.41-1.23; = 0.22); MACE, 0.57 (0.44-0.75; < 0.0001): 0.56 (0.43-0.74, < 0.0001) in China, 0.58 (0.27-1.23, = 0.16) elsewhere.
CONCLUSION
No GT strategy affected MB. Overall, genotype-GT but not PFT-GT reduced MACE. However, genotype-GT and PFT-GT reduced MACE in China, but not elsewhere. PFT-GT performed poorly compared to HTPR-Therapy, likely due to inaccurate identification of HTPR patients by PFT.
Topics: Percutaneous Coronary Intervention; Humans; Randomized Controlled Trials as Topic; Purinergic P2Y Receptor Antagonists; Platelet Function Tests; Platelet Aggregation Inhibitors; Hemorrhage; Blood Platelets; Treatment Outcome; Receptors, Purinergic P2Y12; Coronary Artery Disease; Genotype
PubMed: 37549688
DOI: 10.1055/a-2149-4344 -
International Journal of Molecular... Apr 2023The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years... (Review)
Review
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health concern. Three years since its origin, despite the approval of vaccines and specific treatments against this new coronavirus, there are still high rates of infection, hospitalization, and mortality in some countries. COVID-19 is characterised by a high inflammatory state and coagulation disturbances that may be linked to purinergic signalling molecules such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), and purinergic receptors (P1 and P2). These nucleotides/nucleosides play important roles in cellular processes, such as immunomodulation, blood clot formation, and vasodilation, which are affected during SARS-CoV-2 infection. Therefore, drugs targeting this purinergic pathway, currently used for other pathologies, are being evaluated in preclinical and clinical trials for COVID-19. In this review, we focus on the potential of these drugs to control the release, degradation, and reuptake of these extracellular nucleotides and nucleosides to treat COVID-19. Drugs targeting the P1 receptors could have therapeutic efficacy due to their capacity to modulate the cytokine storm and the immune response. Those acting in P2X7, which is linked to NLRP3 inflammasome activation, are also valuable candidates as they can reduce the release of pro-inflammatory cytokines. However, according to the available preclinical and clinical data, the most promising medications to be used for COVID-19 treatment are those that modulate platelets behaviour and blood coagulation factors, mainly through the P2Y12 receptor.
Topics: Humans; Nucleosides; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Adenosine Triphosphate; Adenosine Diphosphate; Receptors, Purinergic
PubMed: 37175571
DOI: 10.3390/ijms24097865 -
International Journal of Molecular... Feb 2023Neurogenic detrusor overactivity (NDO) is a severe lower urinary tract disorder, characterized by urinary urgency, retention, and incontinence, as a result of a... (Review)
Review
Neurogenic detrusor overactivity (NDO) is a severe lower urinary tract disorder, characterized by urinary urgency, retention, and incontinence, as a result of a neurologic lesion that results in damage in neuronal pathways controlling micturition. The purpose of this review is to provide a comprehensive framework of the currently used animal models for the investigation of this disorder, focusing on the molecular mechanisms of NDO. An electronic search was performed with PubMed and Scopus for literature describing animal models of NDO used in the last 10 years. The search retrieved 648 articles, of which reviews and non-original articles were excluded. After careful selection, 51 studies were included for analysis. Spinal cord injury (SCI) was the most frequently used model to study NDO, followed by animal models of neurodegenerative disorders, meningomyelocele, and stroke. Rats were the most commonly used animal, particularly females. Most studies evaluated bladder function through urodynamic methods, with awake cystometry being particularly preferred. Several molecular mechanisms have been identified, including changes in inflammatory processes, regulation of cell survival, and neuronal receptors. In the NDO bladder, inflammatory markers, apoptosis-related factors, and ischemia- and fibrosis-related molecules were found to be upregulated. Purinergic, cholinergic, and adrenergic receptors were downregulated, as most neuronal markers. In neuronal tissue, neurotrophic factors, apoptosis-related factors, and ischemia-associated molecules are increased, as well as markers of microglial and astrocytes at lesion sites. Animal models of NDO have been crucial for understanding the pathophysiology of lower urinary tract (LUT) dysfunction. Despite the heterogeneity of animal models for NDO onset, most studies rely on traumatic SCI models rather than other NDO-driven pathologies, which may result in some issues when translating pre-clinical observations to clinical settings other than SCI.
Topics: Female; Rats; Animals; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urinary Incontinence; Spinal Cord Injuries; Models, Animal; Urodynamics
PubMed: 36834694
DOI: 10.3390/ijms24043273 -
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 -
American Journal of Obstetrics and... Jan 2023The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies... (Review)
Review
OBJECTIVE
The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.
DATA SOURCES
We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.
STUDY ELIGIBILITY CRITERIA
Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.
METHODS
A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.
RESULTS
A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.
CONCLUSION
Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.
Topics: Humans; Urinary Bladder, Overactive; TRPV Cation Channels; Genetic Markers; Cholinergic Antagonists; Receptors, Cholinergic; Receptors, Purinergic; Receptor, Muscarinic M3
PubMed: 35932882
DOI: 10.1016/j.ajog.2022.07.044 -
Frontiers in Bioscience (Landmark... Apr 2022Primary bone cancers are rare malignant diseases with significant morbidity and mortality. The treatment regimen relies on a combination of surgery (often involving...
Primary bone cancers are rare malignant diseases with significant morbidity and mortality. The treatment regimen relies on a combination of surgery (often involving amputation), chemotherapy and radiotherapy with outcomes dependent on localization of the tumour, grade, size and response to chemotherapy. Both treatment options and survival statistics have remained constant over the past 40 years and alternative therapies need to be explored. Purinergic signalling involving the interaction of extracellular nucleotides with P2 receptors has been investigated in numerous cancers with activation or inhibition a topic of debate. To assess whether purinergic signalling could be a viable target in primary bone cancer a systematic review for relevant primary literature published in PubMed, MEDLINE and Web of Science was performed. Search terms were formulated around three separate distinct topics; expression of P2 receptors in primary bone cancer models, P2 receptor signalling pathways involved and the functional consequences of P2 receptor signalling. Searching identified 30 primary articles after screening and eligibility assessments. This review highlights the diverse expression, signalling pathways and functional roles associated with different P2 receptors in primary bone cancers and provides a systematic summary of which P2 receptors are exciting targets to treat primary bone cancer and its associated symptoms.
Topics: Bone Neoplasms; Humans; Nucleotides; Signal Transduction
PubMed: 35468681
DOI: 10.31083/j.fbl2704122 -
The Journal of Headache and Pain Apr 2022Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are... (Review)
Review
BACKGROUND
Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclinical data addressing the role of adenosine in migraine pathophysiology.
METHODS
PubMed and EMBASE were searched for pre-clinical studies on the role of adenosine in migraine pathophysiology on September 5, 2021.
RESULTS
A total of 2510 studies were screened by title and abstract. Of these, thirteen pre-clinical studies evaluating adenosine, adenosine A1, A2A and A3 receptors were included. These studies showed that adenosine signaling pathway is involved in controlling vascular tone. Furthermore, electrical stimulation of the trigeminal ganglion modulates the expression of adenosine A and A receptors in the trigeminal ganglion and trigeminal nucleus caudalis implicating adenosine signaling pathway in pain transmission.
CONCLUSION
Preclinical studies showed that adenosine has a dual effect on vasodilation and trigeminal pain pathway due to different receptor activation, suggesting a possible role of adenosine in migraine pathophysiology. Studies investigating pharmacological characteristics of subtypes of adenosine receptors are needed to further elucidate their role as a potential target for migraine treatment.
Topics: Adenosine; Humans; Migraine Disorders; Signal Transduction; Trigeminal Ganglion; Trigeminal Nuclei
PubMed: 35382738
DOI: 10.1186/s10194-022-01412-0