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Diagnostics (Basel, Switzerland) Jan 2023TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly... (Review)
Review
BACKGROUND
TAR DNA-binding protein 43 (TDP-43) aggregation in neuronal cells is recognized as a hallmark of amyotrophic lateral sclerosis (ALS). Although the literature strongly supports the pathogenetic role of TDP-43 in ALS pathogenesis, the role of TDP-43 as a biomarker of ALS is controversial. We performed a systematic review and meta-analysis to assess the diagnostic performance of TDP-43 for ALS.
METHODS
Relevant publications were identified by a systematic literature search on PubMed and Web of Science from their inception to 8 April 2022.
RESULTS
Seven studies, including 472 individuals, of whom 254 had ALS according to the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, met the inclusion criteria for our meta-analysis. According to the random-effects model, CSF TDP-43 levels are higher in ALS patients compared with control groups.
CONCLUSIONS
CSF TDP-43 could represent a biomarker of ALS, but further studies are mandatory before drawing conclusions.
PubMed: 36766521
DOI: 10.3390/diagnostics13030416 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Journal of Ethnopharmacology Mar 2021The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment...
ETHNOPHARMACOLOGICAL RELEVANCE
The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases.
MATERIALS AND METHODS
A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019.
RESULTS
Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals.
CONCLUSION
Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning.
Topics: Animals; Anthraquinones; Brain; Hepatic Encephalopathy; Humans; Liver; Muscle, Skeletal; Muscular Diseases; Plant Extracts; Prognosis; Seeds; Senna Plant
PubMed: 33011371
DOI: 10.1016/j.jep.2020.113431 -
Archives of Gynecology and Obstetrics Jun 2021The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking.
OBJECTIVE
To provide a clinical characterization of the ProMisE groups of EC.
METHODS
A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated.
RESULTS
Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%.
CONCLUSION
The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.
Topics: Aged; Biomarkers, Tumor; DNA Polymerase II; Endometrial Neoplasms; Female; Genes, p53; Humans; Middle Aged; Mutation; PTEN Phosphohydrolase; Phenotype; Poly-ADP-Ribose Binding Proteins; Prognosis; Risk Assessment; Tumor Suppressor Protein p53
PubMed: 33754186
DOI: 10.1007/s00404-021-06028-4 -
International Journal of Molecular... Jan 2023PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion... (Review)
Review
PURA-related neurodevelopmental disorders (PURA-NDDs) are a rare genetic disease caused by pathogenic autosomal dominant variants in the PURA gene or a deletion encompassing the PURA gene. PURA-NDD is clinically characterized by neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements, and epilepsy. It is generally considered to be central nervous system disorders, with generalized weakness, associated hypotonia, cognitive and development deficits in early development, and seizures in late stages. Although it is classified predominantly as a central nervous syndrome disorder, some phenotypic features, such as myopathic facies, respiratory insufficiency of muscle origin, and myopathic features on muscle biopsy and electrodiagnostic evaluation, point to a peripheral (neuromuscular) source of weakness. Patients with PURA-NDD have been increasingly identified in exome-sequenced cohorts of patients with neuromuscular- and congenital myasthenic syndrome-like phenotypes. Recently, fluctuating weakness noted in a PURA-NDD patient, accompanied by repetitive nerve stimulation abnormalities, suggested the disease to be a channelopathy and, more specifically, a neuromuscular junction disorder. Treatment with pyridostigmine or salbutamol led to clinical improvement of neuromuscular function in two reported cases. The goal of this systematic retrospective review is to highlight the motor symptoms of PURA-NDD, to further describe the neuromuscular phenotype, and to emphasize the role of potential treatment opportunities of the neuromuscular phenotype in the setting of the potential role of PURA protein in the neuromuscular junction and the muscles.
Topics: Humans; Neuromuscular Junction; Myasthenic Syndromes, Congenital; Neurodevelopmental Disorders; Learning Disabilities; Epilepsy; Muscle Hypotonia; Nervous System Malformations; DNA-Binding Proteins; Transcription Factors
PubMed: 36768582
DOI: 10.3390/ijms24032260 -
Movement Disorders : Official Journal... May 2021This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed... (Review)
Review
This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Adolescent; Adult; Anoctamins; Apoptosis Regulatory Proteins; Child; DNA-Binding Proteins; Dystonia; Dystonic Disorders; Genotype; Humans; Molecular Chaperones; Mutation; Phenotype
PubMed: 33502045
DOI: 10.1002/mds.28485 -
Modern Pathology : An Official Journal... Oct 2022Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic...
Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.
Topics: Carcinoma, Adenosquamous; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; ErbB Receptors; Humans; In Situ Hybridization, Fluorescence; Nuclear Proteins; Proto-Oncogene Proteins p21(ras); Salivary Gland Neoplasms; Trans-Activators; Transcription Factors
PubMed: 35871081
DOI: 10.1038/s41379-022-01100-z -
Cancer Reports (Hoboken, N.J.) Mar 2023The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not.
RECENT FINDINGS
Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models.
OBJECTIVE
The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not.
METHODS
A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05.
RESULTS
Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, p = .032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, p = .119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, p = .021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, p = .119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models.
CONCLUSION
Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.
Topics: Humans; DNA-Binding Proteins; X-ray Repair Cross Complementing Protein 1; Squamous Cell Carcinoma of Head and Neck; Genetic Predisposition to Disease; Mouth Neoplasms; Head and Neck Neoplasms
PubMed: 36573562
DOI: 10.1002/cnr2.1776 -
Medicine Aug 2019Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a systematic review and meta-analysis of studies exploring association of some genetic polymorphisms and PC risk.
METHODS
We systematically searched on PubMed and Web of Science for association of genetic polymorphisms and PC risk published from 1969 to January 2019. We computed the multivariate odd ratio (OR) and 95% confidence intervals (CI), comparing different genetic types.
RESULTS
The present meta-analysis showed significant associations between deoxyribonucleic acid (DNA) repair gene (X-ray repair cross-complementing group 1 (XRCC1) Arg399GIn and Arg194Trp, excision repair cross complementation 1 (ERCC1) rs11615 and rs3212986, ERCC2 rs13181) polymorphisms and PC risk.
CONCLUSIONS
Because of the limited sample size and ethnicity enrolled in the present meta-analysis, further larger scaled studies should be performed to demonstrate the association.
Topics: DNA Glycosylases; DNA Repair; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Humans; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein
PubMed: 31393355
DOI: 10.1097/MD.0000000000016541 -
Public Health Genomics 2020The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population...
SNPs in Sites for DNA Methylation, Transcription Factor Binding, and miRNA Targets Leading to Allele-Specific Gene Expression and Contributing to Complex Disease Risk: A Systematic Review.
INTRODUCTION
The complex genetic diversity among human populations results from an assortment of factors acting at various sequential levels, including mutations, population migrations, genetic drift, and selection. Although there are a plethora of DNA sequence variations identified through genome-wide association studies (GWAS), the challenge remains to explain the mechanisms underlying interindividual phenotypic disparity accounting for disease susceptibility. Single nucleotide polymorphisms (SNPs) present in the sites for DNA methylation, transcription factor (TF) binding, or miRNA targets can alter the gene expression. The systematic review aimed to evaluate the complex crosstalk among SNPs, miRNAs, DNA methylation, and TFs for complex multifactorial disease risk.
METHODS
PubMed and Scopus databases were used from inception until May 15, 2019. Initially, screening of articles involved studies assessing the interaction of SNPs with TFs, DNA methylation, or miRNAs resulting in allele-specific gene expression in complex multifactorial diseases. We also included the studies which provided experimental validation of the interaction of SNPs with each of these factors. The results from various studies on multifactorial diseases were assessed.
RESULTS
A total of 11 articles for SNPs interacting with DNA methylation, 30 articles for SNPs interacting with TFs, and 11 articles for SNPs in miRNA binding sites were selected. The interactions of SNPs with epigenetic factors were found to be implicated in different types of cancers, autoimmune diseases, cardiovascular diseases, diabetes, and asthma.
CONCLUSION
The systematic review provides evidence for the interplay between genetic and epigenetic risk factors through allele-specific gene expression in various complex multifactorial diseases.
Topics: Alleles; Binding Sites; DNA Methylation; Epigenesis, Genetic; Gene Expression; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; MicroRNAs; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Transcription Factors
PubMed: 32966991
DOI: 10.1159/000510253