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Cell Communication and Signaling : CCS Dec 2013Cell adhesion molecules (CAMs) play indispensable roles in the developing and mature brain by regulating neuronal migration and differentiation, neurite outgrowth,... (Review)
Review
Cell adhesion molecules (CAMs) play indispensable roles in the developing and mature brain by regulating neuronal migration and differentiation, neurite outgrowth, axonal fasciculation, synapse formation and synaptic plasticity. CAM-mediated changes in neuronal behavior depend on a number of intracellular signaling cascades including changes in various second messengers, among which CAM-dependent changes in intracellular Ca2+ levels play a prominent role. Ca2+ is an essential secondary intracellular signaling molecule that regulates fundamental cellular functions in various cell types, including neurons. We present a systematic review of the studies reporting changes in intracellular Ca2+ levels in response to activation of the immunoglobulin superfamily CAMs, cadherins and integrins in neurons. We also analyze current experimental evidence on the Ca2+ sources and channels involved in intracellular Ca2+ increases mediated by CAMs of these families, and systematically review the role of the voltage-dependent Ca2+ channels (VDCCs) in neurite outgrowth induced by activation of these CAMs. Molecular mechanisms linking CAMs to VDCCs and intracellular Ca2+ stores in neurons are discussed.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Cell Adhesion; Cell Adhesion Molecules; Neurons
PubMed: 24330678
DOI: 10.1186/1478-811X-11-94 -
Pain Physician 2015Individual response to opioid analgesics varies among patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individual response to opioid analgesics varies among patients.
OBJECTIVE
This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain.
STUDY DESIGN
A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain.
SETTING
This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain.
METHODS
A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases.
RESULTS
Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms.
LIMITATIONS
Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information.
CONCLUSION
The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management.
Topics: Analgesics, Opioid; Female; Genetic Variation; Humans; Male; Middle Aged; Pain Management; Pain, Postoperative; Polymorphism, Single Nucleotide; Randomized Controlled Trials as Topic; Receptors, Opioid, mu
PubMed: 25794200
DOI: No ID Found -
Journal of Stroke and Cerebrovascular... Jun 2016Brain edema formation is a major cause of brain damages and the high mortality of ischemic stroke. The aim of this review is to explore the relationship between ischemic... (Review)
Review
BACKGROUND
Brain edema formation is a major cause of brain damages and the high mortality of ischemic stroke. The aim of this review is to explore the relationship between ischemic brain edema formation and vasopressin (VP) hypersecretion in addition to the oxygen and glucose deprivation and the ensuing reperfusion injury.
METHODS
Pertinent studies involving ischemic stroke, brain edema formation, astrocytes, and VP were identified by a search of the PubMed and the Web of Science databases in January 2016. Based on clinical findings and reports of animal experiments using ischemic stroke models, this systematic review reanalyzes the implication of individual reports in the edema formation and then establishes the inherent links among them.
RESULTS
This systematic review reveals that cytotoxic edema and vasogenic brain edema in classical view are mainly under the influence of a continuous malfunction of astrocytic plasticity. Adaptive VP secretion can modulate membrane ion transport, water permeability, and blood-brain barrier integrity, which are largely via changing astrocytic plasticity. Maladaptive VP hypersecretion leads to disruptions of ion and water balance across cell membranes as well as the integrity of the blood-brain barrier. This review highlights our current understandings of the cellular mechanisms underlying ischemic brain edema formation and its association with VP hypersecretion.
CONCLUSIONS
VP hypersecretion promotes brain edema formation in ischemic stroke by disrupting hydromineral balance in the neurovascular unit; suppressing VP hypersecretion has the potential to alleviate ischemic brain edema.
Topics: Animals; Astrocytes; Brain; Brain Edema; Brain Ischemia; Humans; Phenotype; Prognosis; Risk Factors; Signal Transduction; Stroke; Up-Regulation; Vasopressins
PubMed: 27068863
DOI: 10.1016/j.jstrokecerebrovasdis.2016.02.002 -
American Journal of Respiratory and... Feb 2024Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as...
BACKGROUND
Chronic Obstructive Pulmonary Disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. This systematic review synthesizes evidence from epigenome-wide association studies (EWAS) related to COPD and lung function.
METHODS
Systematic literature search on PubMed, Embase and CINAHL databases, identified 1947 articles that investigated epigenetic changes associated with COPD/lung function; 17 of them met our eligibility criteria from which data was manually extracted. Differentially methylated positions (DMPs) and/or annotated genes, were considered replicated if identified by ≥2 studies with a p<1 x 10-4.
RESULTS
Ten studies profiled DNA methylation changes in blood and 7 in respiratory samples, including surgically resected lung tissue (n=3), small airways epithelial brushings (n=2), bronchoalveolar lavage (n=1) and sputum (n=1). Main results showed: (1) high variability in study design, covariates and effect sizes, which prevented a formal meta-analysis; (2) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; (3) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and, (4) in COPD vs. control studies, 123 genes (2.6% of total) were shared between ≥1 blood and ≥1 respiratory sample and associated with chronic inflammation, ion transport and coagulation.
CONCLUSIONS
There is high heterogeneity across published COPD/lung function EWAS studies. A few genes (n=123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research.
PubMed: 38422471
DOI: 10.1164/rccm.202302-0231OC -
Human Reproduction Update 2010Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation,... (Review)
Review
BACKGROUND
Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation, gestation and parturition. Abnormal contractility might underlie common and important disorders such as infertility, implantation failure, dysmenorrhea, endometriosis, spontaneous miscarriage or preterm birth.
METHODS
A systematic review of the US National Library of Medicine was performed linking 'uterus' or 'uterine myocyte' with 'calcium ion' (Ca(2+)), 'myosin light chain kinase' and 'myosin light chain phosphatase'. This led to many cross-references involving non-uterine myocytes and, where relevant, these data have been incorporated into the following synthesis.
RESULTS
We have grouped the data according to three main components that determine uterine contractility: the contractile apparatus; electrophysiology of the myocyte including excitation-contraction coupling; and regulation of the sensitivity of the contractile apparatus to Ca(2+). We also have included information regarding potential therapeutic methods for regulating uterine contractility.
CONCLUSIONS
More research is necessary to understand the mechanisms that generate the frequency, amplitude, duration and direction of propagation of uterine contractile activity. On the basis of current knowledge of the molecular control of uterine myocyte function, there are opportunities for systematic testing of the efficacy of a variety of available potential pharmacological agents and for the development of new agents. Taking advantage of these opportunities could result in an overall improvement in reproductive health.
Topics: Actin Cytoskeleton; Calcium Signaling; Electrophysiology; Female; Humans; Models, Biological; Myocytes, Smooth Muscle; Myometrium; Myosin-Light-Chain Kinase; Myosin-Light-Chain Phosphatase; Uterine Contraction; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 20551073
DOI: 10.1093/humupd/dmq016 -
Chemistry, An Asian Journal Nov 2022Nanofluidic memristors are memory resistors based on nanoconfined fluidic systems exhibiting history-dependent ion conductivity. Toward establishing powerful computing... (Review)
Review
Nanofluidic memristors are memory resistors based on nanoconfined fluidic systems exhibiting history-dependent ion conductivity. Toward establishing powerful computing systems beyond the Harvard architecture, these ion-based neuromorphic devices attracted enormous research attention owing to the unique characteristics of ion-based conductors. However, the design of nanofluidic memristor is still at a primary state and a systematic guidance on the rational design of nanofluidic system is desperately required for the development of nanofluidic-based neuromorphic devices. Herein, we proposed a systematic review on the history, main mechanism and potential application of nanofluidic memristors in order to give a prospective view on the design principle of memristors based on nanofluidic systems. Furthermore, based on the present status of these devices, some fundamental challenges for this promising area were further discussed to show the possible application of these ion-based devices.
Topics: Prospective Studies; Electric Conductivity
PubMed: 35994236
DOI: 10.1002/asia.202200682 -
Current Pharmaceutical Design 2017Zinc is a critical metal ion essential for life. The biological significance of zinc is highlighted by the enormous number of proteins (approximately 10% of the human... (Review)
Review
BACKGROUND
Zinc is a critical metal ion essential for life. The biological significance of zinc is highlighted by the enormous number of proteins (approximately 10% of the human proteome) that have zinc-binding capacity. Accordingly, zinc concentrations in cells are tightly regulated by two families of zinc transporter proteins: Slc30a (ZnT) and Slc39a (Zip). ZnT and Zip are known to decrease and increase cytosolic zinc concentrations respectively. Both zinc transporters are suggested to be implicated in a number of disorders and disease states through dysfunctional zinc transport including cancer, diabetes and gastrointestinal (GI) disease.
METHOD
The goal of this work was to identify the role of zinc transporters in GI disease/disorders. Where possible, reference will be made in the context of the function of zinc transporters and their potential role in GI disorders/ diseases with a view towards their possible therapeutic utility in the treatment of these ailments. PubMed was utilized to search for articles with the terms "zinc and GI disease", "zinc transporters and GI disease", "zinc and gut", zinc transporters and gut", and "zinc transporters and intestinal disorders".
RESULTS
We identified a number of reviews on GI disorders/disease states associated with zinc deficiencies, but the very proteins that transport this metal ion in these systems are not well-defined. From a systematic review, we identified the following zinc transporters (Zip1, 2, 4-7, 10, 11 and 14; and ZnT1, 8 and 10) as having some functional role in the GI system and potentially could have a therapeutic role in the treatment of GI disease/disorders.
CONCLUSION
An increasingly common health issue in our communities is disorder/disease of the GI system. Although therapies targeting these disorders are somewhat beneficial, there is a need to develop better, more efficient treatments. Despite that many gut-related disorders/disease states have been analyzed in the context of zinc deficiencies, the transport proteins that move zinc across cells are not well-defined. Zinc transporters are expressed in a range of GI tissue and cells, and their roles in the maintenance, integrity and disease processes of the GI system need to be addressed. This might open a whole new avenue of opportunities for the development of novel therapies targeting these receptors in GI disease states.
Topics: Carrier Proteins; Gastrointestinal Diseases; Humans; Zinc
PubMed: 28120719
DOI: 10.2174/1381612823666170124115850 -
Frontiers in Pharmacology 2022Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for... (Review)
Review
Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (K), and small (SK) and large (BK) conductance calcium-activated K channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K channels can facilitate drug development for the treatment of various K channel-related disorders.
PubMed: 35273505
DOI: 10.3389/fphar.2022.831963 -
The Cochrane Database of Systematic... Mar 2012People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF.
OBJECTIVES
To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data.Most recent search of the Group's register: 22nd August 2011.
SELECTION CRITERIA
Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. Meta-analysis was limited due to differing study designs.
MAIN RESULTS
Five RCTs, with a total of 226 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. In three studies over six months, there was a significant difference found in the difference in relative change in FVC in favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77 to -0.25), although heterogeneity was evident. A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance, in contrast to pre-treatment with placebo. There were no significant differences identified in other clinically relevant outcomes.
AUTHORS' CONCLUSIONS
We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.
Topics: Amiloride; Cystic Fibrosis; Humans; Mucus; Randomized Controlled Trials as Topic; Respiration; Saline Solution, Hypertonic; Sodium Channel Blockers; Vital Capacity
PubMed: 22419304
DOI: 10.1002/14651858.CD005087.pub3 -
BioMed Research International 2014Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport,... (Review)
Review
Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport, metabolism, cell growth, and hemostasis. Natural copper comprises two stable isotopes, (63)Cu and (65)Cu, and 5 principal radioisotopes for molecular imaging applications ((60)Cu, (61)Cu, (62)Cu, and (64)Cu) and in vivo targeted radiation therapy ((64)Cu and (67)Cu). The two potential ways to produce Cu radioisotopes concern the use of the cyclotron or the reactor. A noncopper target is used to produce noncarrier-added Cu thanks to a chemical separation from the target material using ion exchange chromatography achieving a high amount of radioactivity with the lowest possible amount of nonradioactive isotopes. In recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and nanoparticles for preclinical and clinical research; pathological conditions that influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation, tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We aim to discuss all Cu radioisotopes application focusing on (64)Cu and in particular its form (64)CuCl2 that seems to be the most promising for its half-life, radiation emissions, and stability with chelators, allowing several applications in oncological and nononcological fields.
Topics: Copper Radioisotopes; Humans; Nuclear Medicine; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 24895611
DOI: 10.1155/2014/786463