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Biomolecules Feb 2024Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published.
METHODS
We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology.
RESULTS
A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date.
CONCLUSIONS
It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.
Topics: Child; Adult; Humans; Epilepsy; Mutation; Cerebellum; Phenotype; Brain Injuries; Vesicular Transport Proteins
PubMed: 38540691
DOI: 10.3390/biom14030270 -
Journal of Cellular Physiology Aug 2016Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving... (Review)
Review
Long-chain fatty acid (LCFA) movement into skeletal muscle involves a highly mediated process in which lipid rafts are utilized in the cellular membrane, involving numerous putative plasma membrane-associated LCFA transport proteins. The process of LCFA uptake and oxidation is of particular metabolic significance both at rest and during light to moderate exercise. A comprehensive systematic search of electronic databases was conducted to investigate whether exercise alters protein and/or gene expression of putative LCFA transport proteins. There were 31 studies meeting all eligibility criteria, of these 13 utilized an acute exercise protocol and 18 examined chronic exercise adaptations. Seventeen involved a study design incorporating an exercise stimulus, while the remaining 14 incorporated a combined exercise and diet stimulus. Divergent data relating to acute exercise, as well as prolonged exercise training (≥3 weeks), on protein content (PC) response was identified for proteins CD36, FABPpm and CAV1. Messenger ribonucleic acid (mRNA) data did not always correspond to functional PC, supporting previous suggestions of a disconnect due to potentially limiting factors post gene expression. The large array of study designs, cohorts, and primary dependent variables within the studies included in the present review elucidate the complexity of the interaction between exercise and LCFA transport proteins. Summary of the results in the present review validate the need for further targeted investigation within this topic, and provide an important information base for such research. J. Cell. Physiol. 231: 1671-1687, 2016. © 2015 Wiley Periodicals, Inc.
Topics: Exercise; Fatty Acid Transport Proteins; Fatty Acids; Gene Expression Regulation; Humans; Muscle Contraction; Muscle, Skeletal; RNA, Messenger; Signal Transduction; Time Factors
PubMed: 26638980
DOI: 10.1002/jcp.25281 -
Canadian Journal of Psychiatry. Revue... Dec 2021Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to...
BACKGROUND
Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to treat aberrant behaviors and mood symptoms, frequently resulting in polypharmacy and drug-related adverse effects. Pharmacogenomic (PGx) studies with ASD and/or ID (ASD/ID) have been scarce despite the promise of optimizing treatment outcomes. We reviewed the literature on PGx studies with antipsychotics and antidepressants (e.g., treatment response and adverse effects) in ASD/ID.
METHODS
We performed a systematic review using MEDLINE, Embase, and PsycINFO, including peer-reviewed original articles in English referring to PGx in the treatment of ASD/ID in any age groups (e.g., treatment response and adverse effects).
RESULTS
A total of 28 PGx studies using mostly candidate gene approaches were identified across age groups. Notably, only 3 studies included adults with ASD/ID while the other 25 studies focused specifically on children/adolescents with ASD/ID. Twelve studies primarily investigated treatment response, of which 5 and 6 studies included patients treated with antipsychotics and antidepressants, respectively. Most interesting results for response were reported for 2 sets of candidate gene studies, namely: (1) The (rs6280) polymorphism was examined in patients treated with risperidone in 3 studies, 2 of which reported an association with risperidone treatment response and (2) the 5-HTTLPR polymorphism and treatment response to antidepressants which was investigated in 4 studies, 3 of which reported significant associations. In regard to side effects, 9 of 15 studies focused on hyperprolactinemia in patients treated with risperidone. Among them, 7 and 5 studies examined the impact of and polymorphisms, respectively, yielding mostly negative study findings.
CONCLUSIONS
There is limited data available on PGx in individuals with ASD/ID and in particular in adults. Given the potential for PGx testing in improving treatment outcomes, additional PGx studies for psychotropic treatment in ASD/ID across age groups are warranted.
Topics: Adolescent; Adult; Antipsychotic Agents; Autism Spectrum Disorder; Child; Humans; Intellectual Disability; Pharmacogenomic Testing; Psychotropic Drugs; Serotonin Plasma Membrane Transport Proteins
PubMed: 33222504
DOI: 10.1177/0706743720971950 -
Urologic Oncology May 2022Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated. This study aims to define gene expression profiles in MIBC and to identify potential candidate genes and pathways.
OBJECTIVES
To review and evaluate gene expression studies in MIBC through publicly available RNA sequencing (RNA-Seq) and microarray data in order to identify potential prognostic and therapeutic targets for MIBC.
METHODS
A systematic literature search of the Ovid MEDLINE, PubMed, and Wiley Cochrane Central Register of Controlled Trials databases was performed using the terms "gene," "gene expression," and "bladder cancer" January 1, 1990 through March 2021 focused on populations with MIBC.
RESULTS
In the final analysis, GEO datasets were included. Fixed effect model was employed in the meta-analysis. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in MIBC were performed using ImaGEO and GeneMANIA software. A heatmap for the upregulated and downregulated genes was generated along with the correlated pathways.
CONCLUSION
A total of 9 genes were reported in this analysis. Six genes were reported as upregulated (ProTα, SPINT1, UBE2E1, RAB25, KPNB1, HDAC1) and 3 genes as downregulated (NUP188, IPO13, NUP124). Genes were found to be involved in "ubiquitin mediated proteolysis," "protein processing in endoplasmic reticulum," "transcriptional misregulation in cancer," and "RNA transport" pathways.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Muscles; Neoplasm Invasiveness; Prognosis; Urinary Bladder Neoplasms; rab GTP-Binding Proteins
PubMed: 35039218
DOI: 10.1016/j.urolonc.2021.11.003 -
Critical Reviews in Food Science and... 2022Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due...
Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due to its multiple functions. Research on its mode of action reveals that intact Lf or its active peptide (i.e., lactoferricin) shows an important multifunctional performance. Oral delivery is considered as the most convenient administration route for this bioactive protein. Unfortunately, Lf is sensitive to the gastrointestinal (GI) physicochemical stresses and lactoferricin is undetectable in GI digesta. This review introduces the functionality of Lf at the molecular level and its degradation behavior in GI tract is discussed in detail. Subsequently, the absorption and transport of Lf from intestine into the blood circulation, which is pivotal to its health promoting effects in various tissues, and some assisting labeling methods are discussed. Stabilization technologies aiming at preserving the structural integrity and functional properties of orally administrated Lf are summarized and compared. Altogether, this work comprehensively reviews the structure-function relationship of Lf, its oral fate and the development of stabilization technologies for the enhancement of the oral bioavailability of Lf. The existing limitations and scope for future research are also discussed.
Topics: Animals; Chemical Phenomena; Gastrointestinal Tract; Lactoferrin; Milk
PubMed: 33749401
DOI: 10.1080/10408398.2021.1900774 -
Biological Psychiatry Sep 2010The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44-base... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44-base pair-long region gives rise to short "S" and long "L" forms of the promoter region, the "S" form being associated with reduced serotonin transporter expression.
METHODS
A systematic review and meta-analysis was performed to clarify the effect of 5-HTTLPR on antidepressant response and remission rates. Data were obtained from 28 studies with 5408 participants. Three genotype comparisons were tested-SS versus (SL or LL), (SS or SL) versus LL, and SS versus LL.
RESULTS
There was no statistically significant effect on antidepressant response. Compared with L carriers, there was an apparent effect of the SS genotype on remission rate (relative risk: .88; 95% confidence interval: .79-.98; p = .02). However, after trim and fill correction for missing data, the effect disappeared (relative risk: .92; 95% confidence interval: .81-1.05; p = .23), indicating that the initial significant effect was likely the result of publication bias. No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL. Substantial unexplained heterogeneity of effect sizes was observed between studies, pointing to additional interacting factors contributing to an association in some cases.
CONCLUSIONS
The 5-HTTLPR biallelic short/long polymorphism by itself does not seem to usefully predict antidepressant response.
Topics: Alleles; Antidepressive Agents; Depressive Disorder; Genotype; Humans; Polymorphism, Genetic; Promoter Regions, Genetic; Remission Induction; Serotonin Plasma Membrane Transport Proteins
PubMed: 20615496
DOI: 10.1016/j.biopsych.2010.04.034 -
Journal of Oral Pathology & Medicine :... Nov 2023CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its... (Review)
Review
BACKGROUND
CTNNB1 gene encodes beta catenin, a transcriptional activator of Wnt pathway involved in the pathogenesis of odontogenic lesions. Though located intramembranously, its translocation into cytoplasm and nucleus could trigger cell proliferation, inhibition of apoptosis, invasion and migration of the tumour cell.
MATERIALS AND METHODS
Five electronic databases including MEDLINE by PubMed, Google scholar, Scopus, Trip, Cochrane library and EMBASE until 1 January 2023 without period restriction were thoroughly searched. Those articles that identified CTNNB1 mutation and beta catenin in odontogenic lesions were included for review. Risk of bias was analysed for each study using QUADAS 2 tool and Review Manager 5.3 was used to output its result.
RESULTS
Thirty four published articles were included for data synthesis. A total of 1092 cases of odontogenic lesions were assessed for both CTNNB1 mutation and beta catenin expression. CTNNB1 mutation was observed in ameloblastoma, calcifying odontogenic cyst, calcifying cystic odontogenic tumour and all malignant odontogenic tumours. The beta catenin expression (nuclear and cytoplasmic) was maximum in odontogenic keratocyst and calcifying odontogenic cyst. The expression was variable in ameloblastomas, membranous in odontomas, calcifying cystic odontogenic tumour and nuclear in all malignant tumours.
DISCUSSION AND CONCLUSION
High recurrence of odontogenic keratocyst and aggressiveness of solid ameloblastoma and malignant odontogenic tumours could be associated with the nuclear translocation of beta catenin. Disparity between CTNNB1 mutation and beta catenin expression within odontogenic lesions suggests alternate routes of beta catenin activation. The review results support the unique localisation of beta catenin as a helpful diagnostic factor in the pathogenesis of odontogenic lesions.
Topics: Humans; Ameloblastoma; beta Catenin; Odontogenic Cyst, Calcifying; Odontogenic Cysts; Odontogenic Tumors
PubMed: 37840228
DOI: 10.1111/jop.13487 -
Head and Neck Pathology Mar 2023Intraosseous mucoepidermoid carcinoma (IMEC) and Glandular odontogenic cyst (GOC) are those two pathological entities causing diagnostic dilemma due to the... (Meta-Analysis)
Meta-Analysis Review
Diagnostic Reliability of CRTC1/3::MAML2 Gene Fusion Transcripts in Discriminating Histologically Similar Intraosseous Mucoepidermoid Carcinoma from Glandular Odontogenic Cyst: A Systematic Review and Meta-analysis.
BACKGROUND
Intraosseous mucoepidermoid carcinoma (IMEC) and Glandular odontogenic cyst (GOC) are those two pathological entities causing diagnostic dilemma due to the histopathological similarity. An accurate distinction between the two entities is difficult as both presents with a common radiological and histological similarities. The aim of our systematic review was to establish the diagnostic reliability of CRTC1/3::MAML2 gene fusion for the distinction between IMEC and GOC.
METHODS
A complete electronic literature search was made in MEDLINE by PubMed, Google Scholar, and EMBASE databases. Articles with keywords using molecular genetic findings of CRTC1/3::MAML2 gene fusion transcripts, IMEC and GOC were assessed and included for the systematic review.
RESULTS
Twelve subgroups having both qualitative and quantitative analysis revealed CRTC1/3::MAML2 sensitivity of 100% and specificity of 70.59% in differentiating GOC and IMEC. Fixed-effects model confirmed translocation-negative cases to have a decreased risk of association with IMEC (combined odds ratio 8.770, 95% confidence interval - 2.45 to 31.45, p < 0.002).
CONCLUSIONS
The current evidence supports that in all cases with positive gene fusion transcript of the CRTC1/3::MAML2 was specific for IMEC and was significantly differentiating it from GOC. Whereas cases of IMEC with negative gene fusion transcript pose diagnostic difficulty in differentiating from a GOC which is negative for CRTC1/3::MAML2 expression.
Topics: Humans; DNA-Binding Proteins; Trans-Activators; Carcinoma, Mucoepidermoid; Reproducibility of Results; Transcription Factors; Odontogenic Cysts; Mouth Neoplasms; Gene Fusion; Oncogene Proteins, Fusion
PubMed: 36357765
DOI: 10.1007/s12105-022-01494-x -
Pharmacogenomics 2015Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few... (Meta-Analysis)
Meta-Analysis Review
Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders. In particular, we examine the role of serotonergic genes in the response to pharmacotherapy for alcohol, cocaine and nicotine addiction. Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline.
Topics: Genetic Variation; Humans; Serotonin; Serotonin Agents; Serotonin Plasma Membrane Transport Proteins; Substance-Related Disorders; Tryptophan Hydroxylase
PubMed: 26265436
DOI: 10.2217/pgs.15.72 -
Explaining ADAGIO: a critical review of the biological basis for the clinical effects of rasagiline.Movement Disorders : Official Journal... Nov 2011The ADAGIO study demonstrated a symptomatic benefit for rasagiline in early Parkinson's disease (PD) and suggested a disease-modifying effect. Evidence indicates that... (Review)
Review
The ADAGIO study demonstrated a symptomatic benefit for rasagiline in early Parkinson's disease (PD) and suggested a disease-modifying effect. Evidence indicates that mitochondrial dysfunction plays a role in the pathogenesis of PD and that this may be the site of effect for rasagiline. In this systematic review, evidence for the role of mitochondria in the pathogenesis of PD are reviewed in light of other proposed mechanisms of neuronal degeneration and the actions of rasagiline and its component parts, namely propargylamine and the metabolite, aminoindan. Evidence for the role of mitochondria in the pathogenesis and treatment of PD are reviewed in light of other proposed mechanisms of neuronal degeneration and clinical actions of rasagiline. Monoamine oxidase B (MAO-B) located in the outer mitochondrial membrane controls dopamine metabolism in early PD, and this is the likely location for the symptomatic action of rasagiline. Accumulating evidence indicates that mitochondrial impairment contributes to dopaminergic neuronal loss in PD, either directly or through other mechanisms such as oxidative stress or protein misfolding. Further rasagiline affects numerous mitochondrial mechanisms that prevent apoptotic cell death including prevention of opening of the mitochondrial transition pore, decreased release of cytochrome C, alterations in pro-antiapoptotic genes and proteins, and the nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Thus, the functional neuroprotective actions of rasagiline may not be dependent on MAO-B inhibition, but rather may involve actions of the propargylamine moiety and the aminoindan metabolite. An accumulating body of literature indicates a mitochondrial site of action for rasagiline and highlights the neuroprotective action of the drug, providing strong biological plausibility for disease-modifying effects of the drug such as those observed in ADAGIO.
Topics: Animals; Cell Death; Clinical Trials as Topic; Humans; Indans; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurons; Neuroprotective Agents; Parkinson Disease
PubMed: 21953831
DOI: 10.1002/mds.23926