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International Journal of Molecular... Nov 2021Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of... (Review)
Review
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.
Topics: Actin Cytoskeleton; Bacterial Toxins; Cell Line; Enterotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; rho GTP-Binding Proteins
PubMed: 34830494
DOI: 10.3390/ijms222212610 -
Methods in Molecular Biology (Clifton,... 2018The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing...
The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing and regulation of actin cytoskeleton. Over the past decades, accumulating experimental work has increasingly mapped out the mechanistic details and interactions between members of the family and their regulators, establishing detailed interaction circuits within the Rho GTPase signaling network. These circuits have served as a vital foundation based on which a multitude of mathematical models have been developed to explain experimental data, gain deeper insights into the biological phenomenon they describe, as well as make new testable predictions and hypotheses. Due to the diverse nature and purpose of these models, they often vary greatly in size, scope, complexity, and formulation. Here, we provide a systematic, categorical, and comprehensive account of the recent modeling studies of Rho family GTPases, with an aim to offer a broad perspective of the field. The modeling limitations and possible future research directions are also discussed.
Topics: Animals; Computer Simulation; Humans; Models, Biological; Signal Transduction; rho GTP-Binding Proteins
PubMed: 30062401
DOI: 10.1007/978-1-4939-8612-5_1 -
Clinical Journal of the American... Oct 2018Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact...
BACKGROUND AND OBJECTIVES
Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
RESULTS
We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
CONCLUSIONS
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.
Topics: Environmental Exposure; Environmental Pollutants; Fluorocarbon Polymers; Humans; Kidney Diseases
PubMed: 30213782
DOI: 10.2215/CJN.04670418 -
Early Human Development Apr 2019Every year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and...
BACKGROUND
Every year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and often painful procedures as part of routine life-saving care within the neonatal intensive care unit (NICU). Preterm birth continues to be a major health issue associated with increased risk of neurodevelopmental and behavioral disorders such as cerebral palsy, cognitive impairment, autism spectrum disorders and psychiatric disease.
OBJECTIVE
This paper identifies epigenetic alterations and incidence of telomere erosion that have been studied in preterm infants while in the NICU and as a long-term outcome measure. Better understanding of epigenetic alterations and telomere erosion might aid in early detection and prevention/alleviation of the negative effects of cumulative painful/stressful experiences in this population.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were used to guide this review. Systematic searches of databases included PubMed, CINAHL, SCOPUS and PsychInfo.
RESULTS
Twenty-one studies were included, appraised and then synthesized into a narrative summary.
DISCUSSION
Several putative epigenetic markers were identified although there was a paucity of studies related to telomere length. The interaction of disease entity combined with therapeutic interventions intended to treat may inadvertently increase infant allostatic load or ability to adapt to stress. Future research should include not only human studies but leverage newly available large data sets to conduct additional analysis.
Topics: Angiomotins; Brain-Derived Neurotrophic Factor; Epigenesis, Genetic; Humans; Infant, Newborn; Infant, Premature; Insulin-Like Growth Factor II; Intensive Care Units, Neonatal; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Microfilament Proteins; NF-KappaB Inhibitor alpha; Neurodevelopmental Disorders; Receptors, Glucocorticoid; Stress, Physiological; Tacrolimus Binding Proteins; Telomere
PubMed: 30870624
DOI: 10.1016/j.earlhumdev.2019.03.003 -
Pathology, Research and Practice Dec 2019The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.
METHOD
We searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.
RESULTS
Sixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43-1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19-3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17-3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08-6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23-2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).
CONCLUSIONS
High CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.
Topics: Biomarkers, Tumor; Female; Humans; Lymphatic Metastasis; Male; Microfilament Proteins; Middle Aged; Neoplasm Staging; Neoplasms; Nuclear Proteins; Risk Factors; Sex Factors; Signal Transduction
PubMed: 31685300
DOI: 10.1016/j.prp.2019.152683 -
BMC Cardiovascular Disorders Oct 2020This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS).
METHODS
Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR).
RESULTS
Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = - 32.26; 95% CI: - 56.48 to - 8.76; P < 0.01; VASP-PRI: WMD = - 9.61; 95% CI: - 14.63 to - 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12-0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08-1.81; P = 0.01).
CONCLUSIONS
Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.
Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cell Adhesion Molecules; Female; Humans; Male; Microfilament Proteins; Middle Aged; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome
PubMed: 33004000
DOI: 10.1186/s12872-020-01603-0 -
Coronary Artery Disease Aug 2021There is a need to identify genetic factors that may produce coronary artery atherosclerotic disease (CAD) that are not involved in the usual risk factors leading to...
OBJECTIVE
There is a need to identify genetic factors that may produce coronary artery atherosclerotic disease (CAD) that are not involved in the usual risk factors leading to CAD. Previous studies have often equated coronary artery calcification (CAC) with CAD with coronary stenosis or its sequelae. The objective of this study was to examine the relationship between phosphatase and actin regulator 1 (PHACTR1) single nucleotide polymorphisms (SNPs) and the type of coronary artery disease CAD versus CAC.
METHOD
A systematic review of the literature was conducted to answer the question of whether PHACTR1 gene polymorphisms are associated with coronary artery disease expressed as coronary artery atherosclerosis or CAC.
RESULTS
Eighteen studies spanning seven PHACTR1 SNPs were identified and evaluated for the relationship between PHACTR1 and coronary artery disease. There were significant relationships between rs9349379, rs12526453, and CAD with odds ratios (ORs) (confidence interval) of, respectively, 1.15 (1.13-1.17), 1.13 (1.09-1.17) but not for rs2026458, 1.03 (0.88-1.19). The OR for CAC was 1.22 (1.18-1.26) for rs9349379 and 1.28 (1.21-1.38) for rs12526453.
CONCLUSIONS
Several PHACTR1 specifically rs9349379 and rs12526453 polymorphisms but not rs2026458, are associated with CAD. There are differences in the association of PHACTR1 SNPs with CAC. PHACTR1 warrants more attention and study for the prevention and treatment of CAD.
Topics: Atherosclerosis; Coronary Artery Disease; Coronary Stenosis; Genetic Predisposition to Disease; Humans; Microfilament Proteins; Polymorphism, Single Nucleotide; Vascular Calcification
PubMed: 33660664
DOI: 10.1097/MCA.0000000000000942 -
Revista Espanola de Cardiologia... Apr 2019Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart...
Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart transplant and has been associated with an increased risk of sudden cardiac death. Risk stratification in these patients continues to be challenging. The identification of the specific etiology of the disease is very useful for the early detection of mutation carriers. Genetic study often provides prognostic information and can determine the therapeutic approach. Wide phenotypic variability is observed depending on the mutated gene, the type of mutation, and the presence of additional genetic and environmental factors.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Cardiomyopathy, Dilated; Cytoskeletal Proteins; Desmosomes; Filamins; Genes; Genes, Mitochondrial; Genetic Testing; Humans; Lysosomal-Associated Membrane Protein 2; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Prognosis; RNA-Binding Proteins; Risk Assessment; Sarcomeres
PubMed: 30792015
DOI: 10.1016/j.rec.2018.10.017