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Molecular Brain Sep 2018Genetic studies of major depressive disorder and its associated endophenotypes are useful for the identification of candidate genes. In recent years, variations in...
Genetic studies of major depressive disorder and its associated endophenotypes are useful for the identification of candidate genes. In recent years, variations in non-coding RNA genes, such as miRNAs, have been explored as novel candidates for psychiatric disorders and related endophenotypes. The aim of the present study was to evaluate the possible association between a functional polymorphism (rs12720208) in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms in young adults. A sample of 270 participants from Colombia were evaluated with the Hospital Anxiety and Depression Scale - Depression Subscale (HADS-D) and genotyped for the rs12720208 polymorphism using a TaqMan assay. A lineal regression analysis was used. A statistically significant association of the functional polymorphism in the FGF20 gene (rs12720208) with depressive symptoms was found. It was observed that individuals with the G/A genotype had higher scores for the HADS-D subscale. Our results are the first description in the scientific literature about a significant association between a functional polymorphism in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms.
Topics: Binding Sites; Depression; Female; Fibroblast Growth Factors; Humans; Male; MicroRNAs; Polymorphism, Single Nucleotide; Young Adult
PubMed: 30241547
DOI: 10.1186/s13041-018-0397-0 -
Journal of Colloid and Interface Science Jan 2016Dental bleaching with H2O2 is a common daily practice in dentistry to correct discoloration of anterior teeth. The aim of this study has been to determine whether this...
HYPOTHESIS
Dental bleaching with H2O2 is a common daily practice in dentistry to correct discoloration of anterior teeth. The aim of this study has been to determine whether this treatment of human teeth affects growth, differentiation and activity of osteoclast-like cells, as well as the putative modulatory action of osteostatin and fibroblast growth factor 2 (FGF-2).
EXPERIMENTS
Previously to the in vitro assays, structural, physical-chemical and morphological features of teeth after bleaching were studied. Osteoclast-like cells were cultured on human dentin disks, pre-treated or not with 38% H2O2 bleaching gel, in the presence or absence of osteostatin (100 nM) or FGF-2 (1 ng/ml). Cell proliferation and viability, intracellular content of reactive oxygen species (ROS), pro-inflammatory cytokine (IL-6 and TNFα) secretion and resorption activity were evaluated.
FINDINGS
Bleaching treatment failed to affect either the structural or the chemical features of both enamel and dentin, except for slight morphological changes, increased porosity in the most superficial parts (enamel), and a moderate increase in the wettability degree. In this scenario, bleaching produced an increased osteoclast-like cell proliferation but decreased cell viability and cytokine secretion, while it augmented resorption activity on dentin. The presence of either osteostatin or FGF-2 reduced the osteoclast-like cell proliferation induced by bleaching. FGF-2 enhanced ROS content, whereas osteostatin decreased ROS but increased TNFα secretion. The bleaching effect on resorption activity was increased by osteostatin, but this effect was less evident with FGF-2.
CONCLUSIONS
These findings further confirm the deleterious effects of tooth bleaching by affecting osteoclast growth and function as well as different modulatory actions of osteostatin and FGF-2.
Topics: Adolescent; Adsorption; Adult; Animals; Cell Survival; Cells, Cultured; Dentin; Fibroblast Growth Factors; Flow Cytometry; Humans; Hydrogen Peroxide; Macrophages; Mice; Osteoclasts; Parathyroid Hormone-Related Protein; Particle Size; Peptide Fragments; Reactive Oxygen Species; Surface Properties; Tooth Bleaching; Wettability; Young Adult
PubMed: 26407056
DOI: 10.1016/j.jcis.2015.09.035 -
Genetics and Molecular Research : GMR Oct 2015Genome-wide association studies have reported numerous susceptibility loci for Parkinson's disease (PD). However, there have been few replication studies examining these...
Genome-wide association studies have reported numerous susceptibility loci for Parkinson's disease (PD). However, there have been few replication studies examining these loci in northern Chinese populations. To evaluate the relationships among 3 polymorphic markers located in the fibroblast growth factor 20 and transmembrane protein 175 genes and the genetic susceptibility to PD in northern Chinese subjects, 2 single nucleotide polymorphisms, and 1 insertion/deletion marker (rs591323 in FGF20; rs6599388 and rs142821586 in transmembrane protein 175 near the G-associated kinase/diacylglycerol kinase theta region) were investigated in 313 PD patients and 318 matched controls. Mismatched multiplex polymerase chain reaction-restriction fragment length polymorphism analysis as well as sequence-specific primer polymerase chain reaction and restriction fragment length polymorphism assays were performed. The genotypic frequency of rs591323 differed significantly between the patient and control groups; however, neither rs6599388 nor rs142821586 was associated with PD. We corrected the Hardy-Weinberg disequilibrium for rs6599388, which was previously reported to be common in 4 Asian descent populations into equilibrium status by simultaneously genotyping rs6599388 and rs142821586. In summary, we found that rs591323 was associated with PD but rs6599388 and rs142821586 were not associated with PD in a northern Chinese population.
Topics: Aged; Alleles; Asian People; Case-Control Studies; China; Female; Fibroblast Growth Factors; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; INDEL Mutation; Male; Middle Aged; Odds Ratio; Parkinson Disease; Polymorphism, Single Nucleotide; Potassium Channels
PubMed: 26535683
DOI: 10.4238/2015.October.28.30 -
Translational Psychiatry Feb 2015Pharmacogenetics may allow for a personalized treatment, but a combination with clinical variables may further enhance prediction. In particular, in the present paper,... (Randomized Controlled Trial)
Randomized Controlled Trial
Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder: the result of two pooled RCTs.
Pharmacogenetics may allow for a personalized treatment, but a combination with clinical variables may further enhance prediction. In particular, in the present paper, we investigated early partial improvement (EPI) defined as 20% or more improvement by rating scales 2 weeks after treatment, in combination with selected gene variants as a predictor of treatment outcome in patients with major depressive disorder. Two randomized controlled trials with 168 Japanese depressed patients were used. A stepwise multiple linear regression model with HAM-D score change at week 6 as the dependent variable and genotypes, EPI, baseline HAM-D score, age and sex as independent variables was performed in paroxetine, fluvoxamine and milnacipran, respectively, to estimate the prediction of HAM-D change at week 6. In the paroxetine sample, only EPI (P<0.001) was significantly associated with HAM-D change (n=81, R(2)=0.25, P<0.001). In the fluvoxamine sample, 5-HTTLPR La/Lg, S (P=0.029), FGF2 rs1449683C/T (P=0.013) and EPI (P=0.003) were associated with HAM-D change (n=42, R(2)=0.43, P<0.001). In the milnacipran sample, HTR-1A-1019C/G (P=0.001), ADRA2A-1297C/G (P=0.028) and EPI (P<0.001) were associated with outcome (n=45, R(2)=0.71, P<0.001). EPI in combination with genetic variants could be a useful predictor of treatment outcome and could strengthen the practical use of pharmacogenetic data in clinical practice.
Topics: Age Factors; Antidepressive Agents; Antidepressive Agents, Second-Generation; Cyclopropanes; Depressive Disorder, Major; Female; Fibroblast Growth Factors; Fluvoxamine; Humans; Japan; Male; Middle Aged; Milnacipran; Paroxetine; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT1A; Receptors, Adrenergic, alpha-2; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Treatment Outcome
PubMed: 25710119
DOI: 10.1038/tp.2015.6 -
Scientific Reports Jun 2019Endogenous fibroblast growth factor 20 (FGF20) supports maintenance of dopaminergic neurones within the nigrostriatal pathway. Moreover, direct intracerebral infusion of...
Endogenous fibroblast growth factor 20 (FGF20) supports maintenance of dopaminergic neurones within the nigrostriatal pathway. Moreover, direct intracerebral infusion of FGF20 protects against nigrostriatal tract loss in the 6-hydroxydopamine lesion rat model of Parkinson's disease. Increasing endogenous FGF20 production might provide a less-invasive, more translational way of providing such protection. Accordingly, we adopted a targeted repositioning approach to screen for candidate FDA-approved drugs with potential to enhance endogenous FGF20 production in brain. In silico interrogation of the Broad Institute's Connectivity Map database (CMap), revealed 50 candidate drugs predicted to increase FGF20 transcription, 16 of which had profiles favourable for use in Parkinson's disease. Of these, 11 drugs were found to significantly elevate FGF20 protein production in MCF-7 cells, between two- and four-fold. Four drugs were selected for examination in vivo. Following oral dosing in rats for 7 days, salbutamol and triflusal, but not dimethadione or trazodone, significantly elevated FGF20 levels in the nigrostriatal tract. Preliminary examination in the unilateral 6-hydroxydopamine-lesioned rat revealed a modest but significant protection against nigral cell loss with both drugs. Our data demonstrate the power of targeted repositioning as a method to identify existing drugs that may combat disease progression in Parkinson's by boosting FGF20 levels.
Topics: Albuterol; Animals; Brain; Computer Simulation; Corpus Striatum; Dimethadione; Dopaminergic Neurons; Drug Repositioning; Female; Fibroblast Growth Factors; Humans; MCF-7 Cells; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Rats; Rats, Sprague-Dawley; Salicylates; Substantia Nigra; Trazodone; Treatment Outcome
PubMed: 31171821
DOI: 10.1038/s41598-019-44803-1