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Radiotherapy and Oncology : Journal of... Aug 2021Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be... (Review)
Review
Linear Energy Transfer (LET) is widely used to express the radiation quality of ion beams, when characterizing the biological effectiveness. However, averaged LET may be defined in multiple ways, and the chosen definition may impact the resulting reported value. We review averaged LET definitions found in the literature, and quantify which impact using these various definitions have for different reference setups. We recorded the averaged LET definitions used in 354 publications quantifying the relative biological effectiveness (RBE) of hadronic beams, and investigated how these various definitions impact the reported averaged LET using a Monte Carlo particle transport code. We find that the kind of averaged LET being applied is, generally, poorly defined. Some definitions of averaged LET may influence the reported averaged LET values up to an order of magnitude. For publications involving protons, most applied dose averaged LET when reporting RBE. The absence of what target medium is used and what secondary particles are included further contributes to an ill-defined averaged LET. We also found evidence of inconsistent usage of averaged LET definitions when deriving LET-based RBE models. To conclude, due to commonly ill-defined averaged LET and to the inherent problems of LET-based RBE models, averaged LET may only be used as a coarse indicator of radiation quality. We propose a more rigorous way of reporting LET values, and suggest that ideally the entire particle fluence spectra should be recorded and provided for future RBE studies, from which any type of averaged LET (or other quantities) may be inferred.
Topics: Humans; Linear Energy Transfer; Monte Carlo Method; Proton Therapy; Protons; Radiobiology; Relative Biological Effectiveness
PubMed: 33894298
DOI: 10.1016/j.radonc.2021.04.007 -
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 -
Revista de Neurologia Jan 2015We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating... (Review)
Review
We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating different targets, such as those related with mitochondria, acetylcholinesterase activity or intraneuronal calcium levels, perhaps thanks to its action upon the N-methyl-D-aspartate-type receptor, which belongs to the glutamate family. The findings published on the possible effect of latrepirdine in protein aggregation processes in disorders such as Alzheimer's disease and Parkinson's disease are quite controversial. Likewise, the possible neuroprotective effect of latrepirdine has been evaluated in animal models of neurodegenerative diseases, again with heterogeneous results. Consequently, it can be concluded that no preclinical scientific evidence has been found to justify carrying out clinical trials.
Topics: Animals; Biological Availability; Calcium Signaling; Cholinesterase Inhibitors; Disease Models, Animal; Drug Evaluation, Preclinical; Excitatory Amino Acid Antagonists; Humans; Indoles; Mice; Mitochondria; Molecular Structure; Motor Neurons; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Parkinsonian Disorders; Protein Aggregation, Pathological; Rabbits; Rats; Receptors, N-Methyl-D-Aspartate; Tissue Distribution
PubMed: 25522862
DOI: No ID Found -
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 Journal of the American... Aug 2015Neutral-pH, low-glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A... (Meta-Analysis)
Meta-Analysis Review
Effect of Neutral-pH, Low-Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis.
BACKGROUND AND OBJECTIVES
Neutral-pH, low-glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers.
RESULTS
Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =-110; 95% confidence interval, -312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06).
CONCLUSIONS
The use of neutral-pH, low-glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low-glucose degradation products solutions on hard clinical outcomes.
Topics: Biomarkers; Chi-Square Distribution; Creatinine; Dialysis Solutions; Glucose; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Diseases; Peritoneal Dialysis; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Urination; Urodynamics
PubMed: 26048890
DOI: 10.2215/CJN.05410514 -
Biochimica Et Biophysica Acta.... Jul 2019The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While partially compensatory for each other, isoform-specific intracellular distribution, cell-type expression patterns, and regulatory mechanisms suggest different channel isoforms confer distinct properties to the cell.
SCOPE OF REVIEW
Briefly, established TPC/TRPML functions and interaction partners ('interactomes') are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted. Accordingly, interactomes are compared and contrasted, and subsequently described in detail for TPC1, TPC2, TRPML1, and TRPML3.
MAJOR CONCLUSIONS
TPC interactomes are well-defined, encompassing intracellular membrane organisation proteins. TRPML interactomes are varied, encompassing cardiac contractility- and chaperone-mediated autophagy proteins, alongside regulators of intercellular signalling.
GENERAL SIGNIFICANCE
Comprising recently proposed targets to treat cancers, infections, metabolic disease and neurodegeneration, the advancement of TPC/TRPML understanding is of considerable importance. This review proposes novel directions elucidating TPC/TRPML relevance in health and disease. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
Topics: Animals; Calcium Channels; Calcium Signaling; Humans; Transient Receptor Potential Channels
PubMed: 30395881
DOI: 10.1016/j.bbamcr.2018.10.020 -
The Cochrane Database of Systematic... Jun 2016Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy.
OBJECTIVES
To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects.
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.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016.
SELECTION CRITERIA
Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs.
MAIN RESULTS
Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were judged to have an unclear risk of bias. All four studies documented double-blinding to the intervention, but there is some uncertainty with regards to participant blinding in one study. Some outcome data were missing from all four studies.There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between replacement therapy or placebo groups at any time point. Meta-analysis of most respiratory function tests showed no difference between treatment and placebo groups, but the smallest study (n = 16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. A further study reported a significant improvement in forced expiratory volume at one second (litres) at 30 days after participants had received their first dose of favouring the gene therapy agent, but this finding was not confirmed when combined with at second study in the meta-analysis. The more recent study (n = 140) demonstrated a small improvement in forced vital capacity (per cent predicted) at two and three months and again at 11 and 12 months for participants receiving CFTR gene replacement therapy compared to those receiving placebo. The same study reported a significant difference in the relative change in forced expiratory volume at one second (per cent predicted) at two months, three months and 12 months.One small study reported significant concerns with "influenza-like" symptoms in participants treated with CFTR gene replacement therapy; this was not reported on repeated use of the same agent in a larger recent study.There was no other evidence of positive impact on outcomes, in particular improved quality of life or reduced treatment burden.Two studies measured ion transport in the lower airways; one (n = 16) demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). The second study (n = 140) also reported significant changes toward normal values (P = 0.032); however, aggregate data were not available for analysis. In the most recent study, there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance.
AUTHORS' CONCLUSIONS
One study of liposome-based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF, but this limited evidence of efficacy does not support this treatment as a routine therapy at present. There was no evidence of efficacy for viral-mediated gene delivery.Future studies need to investigate clinically important outcome measures.
Topics: Adolescent; Adult; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Gene Transfer Techniques; Genetic Therapy; Humans; Liposomes; Male; Randomized Controlled Trials as Topic; Respiratory Function Tests; Targeted Gene Repair
PubMed: 27314455
DOI: 10.1002/14651858.CD005599.pub5 -
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 -
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 -
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