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European Review For Medical and... Sep 2021Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bipolar disorder (BD) is a severe disorder, and it is associated with an increased risk of mortality. About 25% of patients with BD have attempted and 11% have died by suicide. All these characteristics suggest that the disorders within the bipolar spectrum are a crucial public health problem. With the development of molecular genetics in recent decades, it was possible to more easily detect risk genes associated with this disorder. This study aimed at summarizing the findings of systematic reviews and meta-analyses on the topic and assessing the quality of the available evidence.
MATERIALS AND METHODS
PubMed/Medline and Web of Science were searched to identify systematic reviews and meta-analyses published during 2013-2019. Standard methodology was applied to synthesize and assess the retrieved literature.
RESULTS
This systematic review identifies a number of potential risk genes associated with bipolar disorder whose mechanism of action has yet to be confirmed. They are divided into several groups: 1) a list of the most significant susceptibility genetic factors associated with BD; 2) the implication of the ZNF804A gene in BD; 3) the role of genes involved in calcium signaling in BD; 4) DNA methylation in BD; 5) BD and risk suicide genes; 6) susceptibility genes for early-onset BD; 7) candidate genes common to both BD and schizophrenia; 8) genes involved in cognitive status in BD cases; 9) genes involved in structural alteration in BD brain tissue; 10) genes involved in lithium response in BD.
CONCLUSIONS
Future research should concentrate on molecular mechanisms by which genetic variants play a major role in BD. Supplemental research is needed to replicate the applicable results.
Topics: Bipolar Disorder; Calcium Signaling; DNA Methylation; Genes, Transgenic, Suicide; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Kruppel-Like Transcription Factors; Schizophrenia
PubMed: 34604962
DOI: 10.26355/eurrev_202109_26789 -
Clinical Nutrition ESPEN Jun 2023Cystic fibrosis (CF) is a multisystem disease that can compromise several human body organs. The autosomal recessive genetic disorder is caused by different mutations in... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Cystic fibrosis (CF) is a multisystem disease that can compromise several human body organs. The autosomal recessive genetic disorder is caused by different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for chloride ion transport across apical membranes of epithelial cells in tissues and bicarbonate secretion. In this study, we provide a systematic review of the profile of the intestinal microbiota of cystic fibrosis individuals.
METHODS
The review was conducted according to Preferred Items of Reports for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed/MEDLINE and Scopus databases were searched for relevant articles until Jully 2022.
RESULTS
Eighteen studies (1304 participants) met the inclusion criteria. The quality and bias was assessed using the Methodological index for non-randomized studies (MINORS) tool, with the majority of the studies indicating medium to high quality. Results showed significant changes in the composition of the intestinal microbiota of the individuals with CF compared with healthy controls, with increased of Enterococcus, Veillonella, and Streptococcus, and decreased of Bifidobacterium, Roseburia, and Alistipes genus. The intestinal bacterial community of CF patients was marked by a reduction in its richness and diversity.
CONCLUSION
The systematic review suggests a change in the intestinal microbiota of CF individuals, characterized by a reduction in microbial diversity and abundance of some bacterial markers.
Topics: Humans; Cystic Fibrosis; Gastrointestinal Microbiome; Bacteria; Mutation
PubMed: 37202074
DOI: 10.1016/j.clnesp.2023.04.008 -
Molecular Neurobiology Dec 2023Migraine is a complex neurovascular disorder that is characterized by severe behavioral, sensory, visual, and/or auditory symptoms. It has been labeled as one of the ten... (Review)
Review
Migraine is a complex neurovascular disorder that is characterized by severe behavioral, sensory, visual, and/or auditory symptoms. It has been labeled as one of the ten most disabling medical illnesses in the world by the World Health Organization (Aagaard et al Sci Transl Med 6(237):237ra65, 2014). According to a recent report by the American Migraine Foundation (Shoulson et al Ann Neurol 25(3):252-9, 1989), around 148 million people in the world currently suffer from migraine. On the basis of presence of aura, migraine is classified into two major subtypes: migraine with aura (Aagaard et al Sci Transl Med 6(237):237ra65, 2014) and migraine without aura. (Aagaard K et al Sci Transl Med 6(237):237ra65, 2014) Many complex genetic mechanisms have been proposed in the pathophysiology of migraine but specific pathways associated with the different subtypes of migraine have not yet been explored. Various approaches including candidate gene association studies (CGAS) and genome-wide association studies (Fan et al Headache: J Head Face Pain 54(4):709-715, 2014). have identified the genetic markers associated with migraine and its subtypes. Several single nucleotide polymorphisms (Kaur et al Egyp J Neurol, Psychiatry Neurosurg 55(1):1-7, 2019) within genes involved in ion homeostasis, solute transport, synaptic transmission, cortical excitability, and vascular function have been associated with the disorder. Currently, the diagnosis of migraine is majorly behavioral with no focus on the genetic markers and thereby the therapeutic intervention specific to subtypes. Therefore, there is a need to explore genetic variants significantly associated with MA and MO as susceptibility markers in the diagnosis and targets for therapeutic interventions in the specific subtypes of migraine. Although the proper characterization of pathways based on different subtypes is yet to be studied, this review aims to make a first attempt to compile the information available on various genetic variants and the molecular mechanisms involved with the development of MA and MO. An attempt has also been made to suggest novel candidate genes based on their function to be explored by future research.
PubMed: 38135854
DOI: 10.1007/s12035-023-03837-3 -
Journal of Cardiothoracic Surgery Nov 2022Uniport video-assisted thoracoscopic surgery (VATS) has been applied widely for the treatment of lung cancer in recent years. Some studies have reported that uniport... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Uniport video-assisted thoracoscopic surgery (VATS) has been applied widely for the treatment of lung cancer in recent years. Some studies have reported that uniport VATS might provide better outcomes than multiport VATS. However, the perioperative outcomes of uniport VATS compared with two-port and three-port VATS, respectively, have yet to be studied at a comprehensive scale. This meta-analysis study compares the perioperative efficacy among uniport, two-port, and three-port VATS.
METHODS
We searched studies published before October 1, 2019, by using Web of Science databases, Ovid Medline, Embase, and PubMed. Studies that compared uniport VATS with two-port or three-port VATS for patients with lung cancer were included. Operative time, perioperative blood loss, number of lymph nodes retrieved, conversion rate, duration of postoperative chest tube drainage, length of hospital stay (LoS), visual analogue pain scores on postoperative day (POD) 1 and POD 3, and overall morbidity were evaluated.
RESULTS
Sixteen studies that compared uniport VATS with two-port or three-port VATS in the treatment of lung cancer were included. Uniport VATS showed less blood loss, a shorter duration of postoperative drainage and a lower visual analogue pain score on POD 3 than two-port VATS; it showed a shorter duration of postoperative drainage, a shorter LoS, and lower visual analogue pain scores on POD 1 and POD 3 than three-port VATS. There were no significant differences in the number of lymph nodes retrieved, operative time, conversion rate, and overall morbidity rate when comparing uniport VATS with two-port VATS or three-port VATS.
CONCLUSIONS
Uniport VATS might provide better perioperative outcomes than either two-port or three-port VATS in lung cancer treatment.
Topics: Humans; Thoracic Surgery, Video-Assisted; Lung Neoplasms; Operative Time; Ion Transport; Pain
PubMed: 36348498
DOI: 10.1186/s13019-022-02034-y -
Journal of Environmental Sciences... May 2023Copper (Cu) exists in a variety of forms in different aquatic environments, and affects their bioavailability. In this study we provide a systematic review on toxicity...
Copper (Cu) exists in a variety of forms in different aquatic environments, and affects their bioavailability. In this study we provide a systematic review on toxicity of Cu which focuses on identifying evidence in the mechanisms of Cu toxicity, and apply an adverse outcome pathway (AOP) analysis to identify multiple potential mechanisms and their interactions of Cu toxicity to fish. This analysis process included the mechanisms of behavior toxicant, oxidative toxicant, ion regulation disruption toxicity, as well as endocrine disruption toxicity. It was found that at low levels of Cu exposure, swimming, avoid predators, locating prey and other sensory functions will be impaired, and the organism will suffer from metabolic alkalosis and respiratory acidosis following the inhibition of the carbonic anhydrase active. The main pathway of acute toxicity of Cu to fish is the inhibition of the Na/K-ATPase enzyme, and lead to reduced intracellular sodium absorption, as well as Cu-induced increased cell permeability, in turn resulting in increased sodium ion loss, leading to cardiovascular collapse and respiratory insufficiency. The endocrine disruption toxicity of Cu to fish caused growth inhibition and reproductive reduction. In addition, there are several key pathways of Cu toxicity that are affected by hardness (e.g., Ca) and intracellular DOC concentrations, including inhibiting Cu-induction, improving branchial gas exchange, altering membrane transport functions, decreasing Na loss, and increasing Na uptake. The results of the AOP analysis will provide a robust framework for future directed research on the mechanisms of Cu toxicity.
Topics: Animals; Copper; Adverse Outcome Pathways; Biological Availability; Water Pollutants, Chemical; Sodium; Fishes; Ions
PubMed: 36522080
DOI: 10.1016/j.jes.2022.06.002 -
International Journal of Molecular... Oct 2021The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide...
The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.
Topics: Amiloride; Animals; Epithelial Sodium Channels; Humans; Ion Transport; Lithium; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Protein Structure, Quaternary; Sodium
PubMed: 34681656
DOI: 10.3390/ijms222010998 -
Annals of the New York Academy of... Sep 2021Many aspects of chemistry and biology are mediated by electromagnetic field (EMF) interactions. The central nervous system (CNS) is particularly sensitive to EMF...
Many aspects of chemistry and biology are mediated by electromagnetic field (EMF) interactions. The central nervous system (CNS) is particularly sensitive to EMF stimuli. Studies have explored the direct effect of different EMFs on the electrical properties of neurons in the last two decades, particularly focusing on the role of voltage-gated ion channels (VGCs). This work aims to systematically review published evidence in the last two decades detailing the effects of EMFs on neuronal ion channels as per the PRISM guidelines. Following a predetermined exclusion and inclusion criteria, 22 papers were included after searches on three online databases. Changes in calcium homeostasis, attributable to the voltage-gated calcium channels, were found to be the most commonly reported result of EMF exposure. EMF effects on the neuronal landscape appear to be diverse and greatly dependent on parameters, such as the field's frequency, exposure time, and intrinsic properties of the irradiated tissue, such as the expression of VGCs. Here, we systematically clarify how neuronal ion channels are particularly affected and differentially modulated by EMFs at multiple levels, such as gating dynamics, ion conductance, concentration in the membrane, and gene and protein expression. Ion channels represent a major transducer for EMF-related effects on the CNS.
Topics: Animals; Biological Transport; Biomarkers; Brain; Electromagnetic Fields; Electrophysiological Phenomena; Humans; Ion Channel Gating; Ion Channels; Ions; Neurons; Signal Transduction
PubMed: 33945157
DOI: 10.1111/nyas.14597 -
Molecular Brain Jun 2020The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum...
OBJECTIVES
The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD).
METHODS
A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions.
RESULTS
From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD.
CONCLUSIONS
Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype.
Topics: Autism Spectrum Disorder; Calcium Channels; Calcium Signaling; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Protein Subunits
PubMed: 32571372
DOI: 10.1186/s13041-020-00634-0 -
International Journal of Molecular... Dec 2021Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca) homeostasis....
Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca) homeostasis. Pesticides have been shown to alter Ca homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca overload occurs through two main mechanisms: the entry of Ca from the extracellular medium through the different types of Ca channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca homeostasis.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Calcium, Dietary; Cell Membrane; Homeostasis; Humans; Neuroinflammatory Diseases; Neurotoxicity Syndromes; Oxidative Stress; Pesticides
PubMed: 34948173
DOI: 10.3390/ijms222413376