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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 -
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 -
Dyspnea and reversibility profile of P2Y₁₂ antagonists: systematic review of new antiplatelet drugs.American Journal of Cardiovascular... Aug 2014Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors. (Review)
Review
BACKGROUND
Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.
OBJECTIVE
We aimed to review and quantify the global risk of dyspnea of recent P2Y₁₂ inhibitor drugs, and evaluate its association with the reversibility profile of P2Y₁₂ inhibitors.
METHODS
A database search (March 2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary outcome was the incidence of dyspnea. Placebo-controlled trials were excluded. Meta-analysis was performed and estimates were expressed as risk ratio (RR) and 95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to the reversibility profile of P2Y₁₂ antagonists.
RESULTS
We found eight RCTs including 41,289 patients. Prasugrel was not associated with an increased risk of dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37-2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57-6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly increased the risk of dyspnea compared with the irreversible inhibitor, prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).
CONCLUSIONS
The reversible P2Y₁₂ antagonists ticagrelor, cangrelor, and elinogrel have an increased incidence of dyspnea in increasing order when compared with irreversible P2Y₁₂ inhibitors such as clopidogrel or prasugrel.
Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Dyspnea; Humans; Incidence; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine
PubMed: 24659260
DOI: 10.1007/s40256-014-0071-6 -
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 -
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 -
Lower Urinary Tract Symptoms May 2019Underactive bladder (UAB) is a multifactorial symptom complex often related to detrusor underactivity (DU). Although recognized as a common cause of lower urinary tract...
Underactive bladder (UAB) is a multifactorial symptom complex often related to detrusor underactivity (DU). Although recognized as a common cause of lower urinary tract symptoms and with significant effects on quality of life, UAB/DU is largely underresearched. Herein, we review up-to-date knowledge on the pathophysiological mechanisms of UAB/DU, with an emphasis on the relationship between UAB and bladder outlet obstruction (BOO). Original articles and reviews concerning UAB/DU were identified through a search of the PubMed/Medline and Scopus databases. DU can result from several pathological mechanisms, which can be categorized as idiopathic, neurogenic, myogenic, or functional. The main etiological factors of UAB/DU are aging, diabetes mellitus, neurogenic disorders, and BOO. Although conventional models focus primarily on efferent nerve and myogenic mechanisms, contemporary views highlight the importance of the afferent pathway. Specifically, recent findings in BOO showed that afferent dysfunction, such as altered expression of muscarinic and purinergic P2X receptors or diminished urothelial ATP may play a role in the initial and reversible stages of DU, with potential diagnostic and therapeutic implications.
Topics: Afferent Pathways; Age Factors; Animals; Diabetes Complications; Humans; Nervous System Diseases; Urinary Bladder; Urinary Bladder Neck Obstruction; Urinary Bladder, Underactive
PubMed: 30864243
DOI: 10.1111/luts.12257 -
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 -
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 -
Current Pharmaceutical Design 2019Adenosine receptors (ARs) are classified as A1, A2A, A2B, and A3 subtypes belong to the superfamily of G-protein coupled receptors (GPCRs). More than 40% of modern...
BACKGROUND
Adenosine receptors (ARs) are classified as A1, A2A, A2B, and A3 subtypes belong to the superfamily of G-protein coupled receptors (GPCRs). More than 40% of modern medicines act through either activation or inhibition of signaling processes associated with GPCRs. In particular, A2B AR signaling pathways are implicated in asthma, inflammation, cancer, ischemic hyperfusion, diabetes mellitus, cardiovascular diseases, gastrointestinal disorders, and kidney disease.
METHODS
This article reviews different disease segments wherein A2B AR is implicated and discusses the potential role of subtype-selective A2B AR ligands in the management of such diseases or disorders. All the relevant publications on this topic are reviewed and presented scientifically.
RESULTS
This review provides an up-to-date highlight of the recent advances in the development of novel and selective A2B AR ligands and their therapeutic role in treating various disease conditions. A special focus has been given to the therapeutic potentials of selective A2B AR ligands in the management of airway inflammatory conditions and cancer.
CONCLUSIONS
This systematic review demonstrates the current status and perspectives of A2B AR ligands as therapeutically useful agents that would assist medicinal chemists and pharmacologists in discovering novel and subtype-selective A2B AR ligands as potential drug candidates.
Topics: Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Drug Discovery; Humans; Ligands; Receptor, Adenosine A2B; Signal Transduction
PubMed: 31333084
DOI: 10.2174/1381612825666190717105834