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Familial Cancer Apr 2016In first part of this study, a systematic review was designed to explore the involvement of CYP1A1 and GSTP1 genes in breast cancerogenesis. Based on systematic review,... (Review)
Review
In first part of this study, a systematic review was designed to explore the involvement of CYP1A1 and GSTP1 genes in breast cancerogenesis. Based on systematic review, we designed a study to screen CYP1A1 and GSTP1 genes for mutation and their possible association with breast carcinogenesis. A total of 400 individuals were collected and analyzed by PCR-SSCP. After sequence analysis of coding region of CYP1A1 we identified eleven mutations in different exons of respective gene. Among these eleven mutations, ~3 folds increased breast cancer risk was found associated with Asp82Glu mutation (OR 2.99; 95% CI 1.26-7.09), with Ser83Thr mutation (OR 2.99; 95% CI 1.26-7.09) and with Glu86Ala mutation (OR 3.18; 95% CI 1.27-7.93) in cancer patients compared to controls. Furthermore, ~4 folds increase in breast cancer risk was found associated with Asp347Glu, Phe398Tyr and 5178delT mutations (OR 3.92; 95% CI 1.35-11.3) in patients compared to controls. The sequence analysis of GSTP1 resulted in identification of total five mutations. Among these five mutations, ~3 folds increase in breast cancer risk was observed associated with 1860G>A mutation, with 1861-1876delCAGCCCTCTGGAGTGG mutation (OR 2.70; 95% CI 1.10-6.62) and with 1861C>A mutation (OR 2.97; 95% CI 1.01-8.45) in cancer patients compared to controls. Furthermore, ~5 folds increase in breast cancer risk was associated with 1883G>T mutation (OR 4.75; 95% CI 1.46-15.3) and ~6 folds increase in breast cancer risk was found associated with Iso105Val mutation (OR 6.43; 95% CI 1.41-29.3) in cancer patients compared to controls. Our finding, based on systematic review and experimental data suggest that the polymorphic CYP1A1 and GSTP1 genes may contribute to risk of developing breast cancer.
Topics: Adult; Breast Neoplasms; Case-Control Studies; Cytochrome P-450 CYP1A1; Female; Genetic Association Studies; Genetic Predisposition to Disease; Glutathione S-Transferase pi; Humans; Middle Aged; Mutation; Pakistan; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational
PubMed: 26545608
DOI: 10.1007/s10689-015-9849-1 -
Frontiers in Genetics 2022Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes...
Legume crops provide significant nutrition to humans as a source of protein, omega-3 fatty acids as well as specific macro and micronutrients. Additionally, legumes improve the cropping environment by replenishing the soil nitrogen content. Chickpeas are the second most significant staple legume food crop worldwide behind dry bean which contains 17%-24% protein, 41%-51% carbohydrate, and other important essential minerals, vitamins, dietary fiber, folate, β-carotene, anti-oxidants, micronutrients (phosphorus, calcium, magnesium, iron, and zinc) as well as linoleic and oleic unsaturated fatty acids. Despite these advantages, legumes are far behind cereals in terms of genetic improvement mainly due to far less effort, the bottlenecks of the narrow genetic base, and several biotic and abiotic factors in the scenario of changing climatic conditions. Measures are now called for beyond conventional breeding practices to strategically broadening of narrow genetic base utilizing chickpea wild relatives and improvement of cultivars through advanced breeding approaches with a focus on high yield productivity, biotic and abiotic stresses including climate resilience, and enhanced nutritional values. Desirable donors having such multiple traits have been identified using core and mini core collections from the cultivated gene pool and wild relatives of Chickpea. Several methods have been developed to address cross-species fertilization obstacles and to aid in inter-specific hybridization and introgression of the target gene sequences from wild species. Additionally, recent advances in "Omics" sciences along with high-throughput and precise phenotyping tools have made it easier to identify genes that regulate traits of interest. Next-generation sequencing technologies, whole-genome sequencing, transcriptomics, and differential genes expression profiling along with a plethora of novel techniques like single nucleotide polymorphism exploiting high-density genotyping by sequencing assays, simple sequence repeat markers, diversity array technology platform, and whole-genome re-sequencing technique led to the identification and development of QTLs and high-density trait mapping of the global chickpea germplasm. These altogether have helped in broadening the narrow genetic base of chickpeas.
PubMed: 36035111
DOI: 10.3389/fgene.2022.905771 -
The Cochrane Database of Systematic... Aug 2020In nephrotic syndrome protein leaks from blood into the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While most children with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In nephrotic syndrome protein leaks from blood into the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While most children with nephrotic syndrome respond to corticosteroids, 80% experience a relapsing course. Corticosteroids have reduced the death rate to around 3%. However, corticosteroids have well recognised potentially serious adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, and behavioural disturbances. This is an update of a review first published in 2000 and updated in 2002, 2005, 2007, and 2015.
OBJECTIVES
The aim of this review was to assess the benefits and harms of different corticosteroid regimens in children with steroid-sensitive nephrotic syndrome (SSNS). The benefits and harms of therapy were studied in two groups of children 1) children in their initial episode of SSNS, and 2) children who experience a relapsing course of SSNS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 30 May 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) performed in children (one to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).
MAIN RESULTS
In this 2020 review update 16 new included studies were identified providing a total of 48 included studies with 3941 randomised participants. Risk of bias methodology was often poorly performed with only 25 studies and 22 studies respectively assessed to be at low risk for random sequence generation and allocation concealment. Only nine studies (19%) were at low risk of bias for performance (blinding of participants and personnel) and 11 studies were at low risk of detection bias (blinding of outcome assessment); nine of these studies were placebo-controlled RCTs. Twenty-two studies (fewer than 50%) were at low risk for attrition bias and 23 studies were at low risk for reporting bias (selective outcome reporting). In seven studies, which evaluated children in their initial episode of SSNS and were at low risk of bias for selection bias, there is little or no difference in the number of children with frequent relapses when comparing two months of prednisone with three months or more (RR 0.99, 95% CI 0.82 to 1.19; 585 participants, 4 studies; I2 = 0%) or when comparing three months with five to seven months of therapy (RR 0.99, 95% CI 0.74 to 1.33; 376 participants, 3 studies; I2 = 35%; high certainty evidence). In analyses of eight studies at low risk of selection bias, there is little or no difference in the number of children with any relapse by 12 to 24 months when comparing two months of prednisone with three months or more (RR 0.91, 95% CI 0.78 to 1.06; 637 participants; 5 studies; I2 = 47%) or when comparing three months with five to seven months of therapy (RR 0.88, 95% CI 0.70 to 1.11; 377 participants, 3 studies; I2 = 53%). Little or no difference was noted in adverse effects between the different treatment durations. Among children with relapsing SSNS, two small studies showed that time to remission did not differ between prednisone doses of 1 mg/kg compared with the conventional dose of 2 mg/kg (MD 0.71 days, 95% CI -0.43 to 1.86; 79 participants) and that the total prednisone dose administered was lower (MD -20.60 mg/kg, 95% CI -25.65 to -15.55; 20 participants). Two studies found little or no difference in the number with relapse at six months when comparing dosing by weight with dosing by surface area (RR 1.03, 95% CI 0.71 to 1.49; 146 participants). One study found a reduced risk of relapse with low daily dosing compared with alternate daily dosing (MD -0.90 number of relapses/year, 95% CI -1.33 to -0.47). Four studies found that in children with frequently relapsing disease, daily prednisone during viral infections compared with alternate-day prednisone or no treatment reduced the risk of relapse.
AUTHORS' CONCLUSIONS
There are now four well designed studies randomising 823 children which have clearly demonstrated that there is no benefit of prolonging prednisone therapy beyond two to three months in the first episode of SSNS. Small studies in children with relapsing disease have identified no differences in the times to remission using half the conventional induction dose of 2 mg/kg or 60 mg/m2. It is imperative that a much larger study be carried out to confirm these findings. Lower dose prednisone therapy administered daily during an upper respiratory infection or other infection reduces the risk of relapse compared with continuing alternate-day prednisone or no prednisone based on four small studies. The results of a much larger RCT enrolling more than 300 children are awaited to determine the relative efficacies and adverse effects of using alternate-day compared with daily prednisone to prevent relapse in children with intercurrent infections.
PubMed: 35659203
DOI: 10.1002/14651858.CD001533.pub6 -
L'Encephale Aug 2017The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well documented. Current research tends to indicate that these two factors act in a synergistic manner. The processes underlying this interaction are still poorly known, but epigenetic modifications could be the mediator in the gene/environment interface. The epigenetic mechanisms have been implicated in susceptibility to stress and also in the pathogenesis of psychiatric disorders including depression and schizophrenia. Currently, several studies focus on the consideration of the etiological role of epigenetic regulation in ASD.
OBJECT
The object of this review is to present a summary of current knowledge of an epigenetic hypothesis in ASD, outlining the recent findings in this field.
METHODS
Using Pubmed, we did a systematic review of the literature researching words such as: autism spectrum disorders, epigenetics, DNA methylation and histone modification.
RESULTS
Epigenetic refers to the molecular process modulating gene expression without changes in the DNA sequence. The most studied epigenetic mechanisms are those that alter the chromatin structure including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. In ASD several arguments support the epigenetic hypothesis. In fact, there is a frequent association between ASD and genetic diseases whose epigenetic etiologies are recognized. A disturbance in the expression of genes involved in the epigenetic regulation has also been described in this disorder. Some studies have demonstrated changes in the DNA methylation of several autism candidate genes including the gene encoding the oxytocin receptor (OXTR), the RELN and the SHANK3 genes. Beyond the analysis of candidate genes, recent epigenome-wide association studies have investigated the methylation level of several other genes and showed hypomethylation of the whole DNA in brain and blood samples of autistic patients. The changes in epigenetic marks following exposure to environmental factors known as autism risk factors are also discussed in many reports. They include nutritional (vitamin D and folate) and toxic (sodium valproate, bisphenol A) factors. Despite a considerable contribution to understanding the complexity of ASD etiology, the epigenetic studies suffer from numerous methodological biases that limit the scope of their results and make their interpretation difficult. The cell samples used in the psychiatric studies are mostly from the post-mortem tissue of the central nervous system, and factors that might change the epigenome (age, gender, treatments received…) are not taken into account. The use of blood and buccal epithelium samples raises in turn the question as to whether the epigenome of these cells reflects that of the nerve cells. DNA methylation can also be influenced by cell subcomposition variability, transcriptional variability and by DNA sequence variants.
CONCLUSION
These recent discoveries in epigenetics are the beginnings of an etiopathogenic research revolution in neurodevelopmental disorders. The conceptualization of epigenetic processes is in its early stages and despite its limited means will help integrate disparate data factors previously involved in autism. It could also be the target for the development of new therapeutic modalities.
Topics: Autism Spectrum Disorder; Child; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Reelin Protein
PubMed: 27692350
DOI: 10.1016/j.encep.2016.07.007 -
Cancer Cytopathology Feb 2022Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not... (Meta-Analysis)
Meta-Analysis Review
Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta-analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy-one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59-0.71) and a specificity of 0.99 (CI, 0.93-1.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38-0.57) and 0.62 (CI, 0.53-0.71), respectively. BAP1 loss and CDKN2A HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78-0.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70-0.90) and 0.65 (CI, 0.41-0.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68-0.77) and a specificity of 0.90 (CI, 0.84-0.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and CDKN2A with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.
Topics: Biomarkers, Tumor; Glucose Transporter Type 1; Homozygote; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Sequence Deletion
PubMed: 34478240
DOI: 10.1002/cncy.22509 -
Blood Apr 2016Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course... (Meta-Analysis)
Meta-Analysis Review
Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course has been well recognized. The Rai and Binet staging systems described ∼40 years ago have proven to be robust prognostic tools. Over the past 2 decades, several novel biological, genetic, and molecular markers have been shown to be useful adjuncts to the Rai and Binet staging systems. In this systematic review, we examined the role of immunoglobulin heavy-chain variable region gene (IGHV) mutation status and genetic abnormalities determined by interphase fluorescence in situ hybridization (FISH) in patients with newly diagnosed CLL. The cumulative evidence presented in this systematic review is sufficient to recommend that FISH and IGHV be performed as standard clinical tests for all patients with newly diagnosed CLL in those countries with the resources to do so. In addition to clinical stage, these parameters could represent the minimal standard initial prognostic evaluation for patients with CLL. This approach will allow the application of powerful, recently developed prognostic indices (all of which are dependent on IGHV and FISH results) to all patients with newly diagnosed CLL.
Topics: Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Prognosis
PubMed: 26841802
DOI: 10.1182/blood-2015-10-620864 -
Frontiers in Microbiology 2022Methicillin-resistant (MRSA) is a leading cause of hospital-associated (HA) and community-associated (CA) infections globally. The multi-drug resistant nature of this... (Review)
Review
BACKGROUND
Methicillin-resistant (MRSA) is a leading cause of hospital-associated (HA) and community-associated (CA) infections globally. The multi-drug resistant nature of this pathogen and its capacity to cause outbreaks in hospital and community settings highlight the need for effective interventions, including its surveillance for prevention and control. This study provides an update on the clonal distribution of MRSA in Africa.
METHODS
A systematic review was conducted by screening for eligible English, French, and Arabic articles from November 2014 to December 2020, using six electronic databases (PubMed, EBSCOhost, Web of Science, Scopus, African Journals Online, and Google Scholar). Data were retrieved and analyzed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (registered at PROSPERO: CRD42021277238). Genotyping data was based primarily on multilocus sequence types (STs) and Staphylococcal Cassette Chromosome (SCC) types. We utilized the Phyloviz algorithm in the cluster analysis and categorization of the MRSA STs into various clonal complexes (CCs).
RESULTS
We identified 65 studies and 26 publications from 16 of 54 (30%) African countries that provided sufficient genotyping data. MRSA with diverse staphylococcal protein A () and SCC types in CC5 and CC8 were reported across the continent. The ST5-IV [2B] and ST8-IV [2B] were dominant clones in Angola and the Democratic Republic of Congo (DRC), respectively. Also, ST88-IV [2B] was widely distributed across the continent, particularly in three Portuguese-speaking countries (Angola, Cape Verde, and São Tomé and Príncipe). The ST80-IV [2B] was described in Algeria and Egypt, while the HA-ST239/ST241-III [3A] was only identified in Egypt, Ghana, Kenya, and South Africa. ST152-MRSA was documented in the DRC, Kenya, Nigeria, and South Africa. Panton-Valentine leukocidin (PVL)-positive MRSA was observed in several CCs across the continent. The median prevalence of PVL-positive MRSA was 33% (ranged from 0 to 77%; = 15).
CONCLUSION
We observed an increase in the distribution of ST1, ST22, and ST152, but a decline of ST239/241 in Africa. Data on MRSA clones in Africa is still limited. There is a need to strengthen genomic surveillance capacity based on a "One-Health" strategy to prevent and control MRSA in Africa.
PubMed: 35591993
DOI: 10.3389/fmicb.2022.860436 -
International Journal of Molecular... Aug 2020Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to... (Review)
Review
Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. , , , , , and were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.
Topics: Cyclooxygenase 2; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Histone Code; Histones; Humans; Interferon-gamma; Interleukin-6; Periodontal Diseases; Receptors, Interleukin-6; Suppressor of Cytokine Signaling 1 Protein; Tumor Necrosis Factor-alpha
PubMed: 32867386
DOI: 10.3390/ijms21176217 -
Molecules (Basel, Switzerland) Nov 2021Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such...
Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA-peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Peptides; Signal Transduction
PubMed: 34834147
DOI: 10.3390/molecules26227053 -
Progress in Biophysics and Molecular... May 2023Biomarker-based tests may facilitate Tuberculosis (TB) diagnosis, accelerate treatment initiation, and thus improve outcomes. This review synthesizes the literature on... (Review)
Review
Biomarker-based tests may facilitate Tuberculosis (TB) diagnosis, accelerate treatment initiation, and thus improve outcomes. This review synthesizes the literature on biomarker-based detection for TB diagnosis using machine learning. The systematic review approach follows the PRISMA guideline. Articles were sought using relevant keywords from Web of Science, PubMed, and Scopus, resulting in 19 eligible studies after a meticulous screening. All the studies were found to have focused on the supervised learning approach, with Support Vector Machine (SVM) and Random Forest emerging as the top two algorithms, with the highest accuracy, sensitivity and specificity reported to be 97.0%, 99.2%, and 98.0%, respectively. Further, protein-based biomarkers were widely explored, followed by gene-based such as RNA sequence and, Spoligotypes. Publicly available datasets were observed to be popularly used by the studies reviewed whilst studies targeting specific cohorts such as HIV patients or children gathering their own data from healthcare facilities, leading to smaller datasets. Of these, most studies used the leave one out cross validation technique to mitigate overfitting. The review shows that machine learning is increasingly assessed in research to improve TB diagnosis through biomarkers, as promising results were shown in terms of model's detection performance. This provides insights on the possible application of machine learning approaches to diagnose TB using biomarkers as opposed to the traditional methods that can be time consuming. Low-middle income settings, where access to basic biomarkers could be provided as compared to sputum-based tests that are not always available, could be a major application of such models.
Topics: Child; Humans; Mycobacterium tuberculosis; HIV Infections; Tuberculosis; Biomarkers; Machine Learning
PubMed: 36931609
DOI: 10.1016/j.pbiomolbio.2023.03.001