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Developmental Medicine and Child... Jun 2023To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne... (Meta-Analysis)
Meta-Analysis Review
AIM
To estimate the global prevalence of intellectual developmental disorder (IDD) and the IDD prevalence-genotype association in Becker muscular dystrophy (BMD) or Duchenne muscular dystrophy (DMD) according to the affected isoforms of the DMD gene: Dp427, Dp140, Dp71.
METHOD
Systematic searches in MEDLINE, Scopus, Web of Science, and the Cochrane Library were conducted from inception of each database to March 2022. Observational studies that determined the prevalence of IDD in the population with BMD or DMD were included. Meta-analyses of IDD prevalence and prevalence ratios of the IDD-genotype association were conducted.
RESULTS
Forty-nine studies were included. The prevalence of IDD in BMD was 8.0% (95% confidence interval 5.0-11.0), and in DMD it was 22.0% (18.0-27.0). Meta-analyses of IDD-genotype association showed a deleterious association between IDD and the number of isoforms affected in DMD, with a prevalence ratio = 0.43 (0.28-0.64) and 0.17 (0.09-0.34) for Dp140 /Dp71 versus Dp140 /Dp71 and Dp140 /Dp71 versus Dp140 /Dp71 comparisons respectively. However, in BMD, there was no association for Dp140 /Dp71 versus Dp140 /Dp71 .
INTERPRETATION
There is a high prevalence of IDD in BMD and DMD. Moreover, the number of isoforms affected is strongly and negatively associated with the prevalence of IDD in DMD.
WHAT THIS PAPER ADDS
The global prevalence of intellectual developmental disorder (IDD) was 8% in Becker muscular dystrophy and 22% in Duchenne muscular dystrophy (DMD). The global prevalence of IDD in DMD was 12%, 29%, and 84% in participants with Dp427 /Dp140 /Dp71 , Dp427 /Dp140 /Dp71 , and Dp427 /Dp140 /Dp71 genotypes respectively. In DMD, 12% and 22% of participants had abnormal performance IQ and verbal IQ values respectively.
Topics: Child; Humans; Muscular Dystrophy, Duchenne; Dystrophin; Developmental Disabilities; Prevalence; Intellectual Disability; Protein Isoforms
PubMed: 36440509
DOI: 10.1111/dmcn.15481 -
Molecular Diagnosis & Therapy Jan 2023Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations.
METHODS
We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian-Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes.
RESULTS
Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22, 95% CI 0.04-0.49; KDR gene, SNV rate: 0.1, 95% CI 0.05-0.16). Finally, two tumor suppressor genes were characterized by a high meta-analytic rate of CNVs: CDKN2A/B (CNV rate: 0.59, 95% CI 0.23-0.90) and PTEN (CNV rate: 0.31, 95% CI 0.02-0.95).
CONCLUSION
MBMs harbored actionable molecular alterations that could be exploited as therapeutic targets to improve the poor prognosis of patients.
Topics: Humans; DNA Copy Number Variations; Vascular Endothelial Growth Factor A; Melanoma; Mutation; Brain Neoplasms
PubMed: 36401787
DOI: 10.1007/s40291-022-00623-0 -
International Journal of Molecular... Oct 2022Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform.... (Review)
Review
Adult skeletal muscle fibres are classified as type 1, 2A, 2X, and 2B. These classifications are based on the expression of the dominant myosin heavy chain isoform. Muscle fibre-specific gene expression and proportions of muscle fibre types change during development and in response to exercise, chronic electrical stimulation, or inactivity. To identify genes whose gain or loss-of-function alters type 1, 2A, 2X, or 2B muscle fibre proportions in mice, we conducted a systematic review of transgenic mouse studies. The systematic review was conducted in accordance with the 2009 PRISMA guidelines and the PICO framework. We identified 25 "muscle fibre genes" (, , , , , , , , , , , , , , , , , , , , , , , and ) whose gain or loss-of-function significantly changes type 1, 2A, 2X or 2B muscle fibre proportions in mice. The fact that 15 of the 25 muscle fibre genes are transcriptional regulators suggests that muscle fibre-specific gene expression is primarily regulated transcriptionally. A reanalysis of existing datasets revealed that the expression of and increases and decreases after exercise, respectively. This suggests that these genes help to regulate the muscle fibre adaptation to exercise. Finally, there are many known DNA sequence variants of muscle fibre genes. It seems likely that such DNA sequence variants contribute to the large variation of muscle fibre type proportions in the human population.
Topics: Adult; Mice; Animals; Humans; Muscle Fibers, Skeletal; Myosin Heavy Chains; Protein Isoforms; Electric Stimulation; Muscle, Skeletal; RNA-Binding Proteins; Forkhead Transcription Factors; Nuclear Receptor Co-Repressor 1
PubMed: 36361732
DOI: 10.3390/ijms232112933 -
Frontiers in Pharmacology 2022The nine membrane-delimited eukaryotic adenylyl cyclases are pseudoheterodimers with an identical domain order of seven (nine) distinct subdomains. Bioinformatics show...
The nine membrane-delimited eukaryotic adenylyl cyclases are pseudoheterodimers with an identical domain order of seven (nine) distinct subdomains. Bioinformatics show that the protein evolved from a monomeric bacterial progenitor by gene duplication and fusion probably in a primordial eukaryotic cell around 1.5 billion years ago. Over a timespan of about 1 billion years, the first fusion product diverged into nine highly distinct pseudoheterodimeric isoforms. The evolutionary diversification ended approximately 0.5 billion years ago because the present isoforms are found in the living fossil coelacanth, a fish. Except for the two catalytic domains, C1 and C2, the mAC isoforms are fully diverged. Yet, within each isoform a high extent of conservation of respective subdomains is found. This applies to the C- and N-termini, a long linker region between the protein halves (C1b), two short cyclase-transducing-elements (CTE) and notably to the two hexahelical membrane domains TM1 and TM2. Except for the membrane anchor all subdomains were previously implicated in regulatory modalities. The bioinformatic results unequivocally indicate that the membrane anchors must possess an important regulatory function specifically tailored for each mAC isoform.
PubMed: 36238545
DOI: 10.3389/fphar.2022.1009797 -
International Journal of Cardiology Jan 2023Acute myocardial infarction (AMI) accounts for about 7 million deaths per year worldwide. The early identification of signs and symptoms and the detection of specific... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute myocardial infarction (AMI) accounts for about 7 million deaths per year worldwide. The early identification of signs and symptoms and the detection of specific serological markers of this disease are mandatory to reach a prompt diagnosis and begin potentially life-saving treatment. Point-of-care technologies applied to salivary diagnostics can provide rapid, simple, low-cost, and accurate measurements of specific markers and can also be used in emergency settings. The present systematic review was developed to answer the following question: "Are salivary biomarkers useful in identifying patients with acute myocardial infarction?"
METHODS
Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, we selected 17 papers. The critical appraisal and quality assessment were performed following the National Institute of Health and the classification of the Oxford Center for Evidence-Based Medicine.
RESULTS
Twenty-six salivary biomarkers were explored in association with AMI. Troponins, C-reactive protein, and adiponectin were the most frequently investigated molecules. We found that the evaluated biomarkers had different levels of diagnostic accuracy in discriminating patients with AMI from healthy controls. We also observed a lack of good-quality studies on the association between the occurrence of AMI and the presence of related salivary biomarkers.
CONCLUSIONS
There is evidence that salivary isoforms of cardiac troponin, C-reactive protein, and creatine phosphokinase (CPK) could be useful markers for the prompt diagnosis of AMI. However, the effective use of these markers as possible substitutes for serological markers should be confirmed by further studies that avoid the bias highlighted in the present review.
Topics: Humans; C-Reactive Protein; Myocardial Infarction; Biomarkers; Troponin; Adiponectin
PubMed: 36167219
DOI: 10.1016/j.ijcard.2022.09.043 -
Biomedicines Jun 2022Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, -glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
PubMed: 35884816
DOI: 10.3390/biomedicines10071511 -
ACS Chemical Biology Jun 2022Zinc-dependent histone deacetylases (HDACs) and sirtuins (SIRT) represent two different classes of enzymes which are responsible for deacylation of modified lysine side...
Zinc-dependent histone deacetylases (HDACs) and sirtuins (SIRT) represent two different classes of enzymes which are responsible for deacylation of modified lysine side chains. The repertoire of acyl residues on lysine side chains identified is rapidly growing, and very recently lysine lactoylation was described to be involved in metabolic reprogramming. Additionally, lysine pyruvoylation represents a marker for aging and liver cirrhosis. Here, we report a systematic analysis of acyl-specificity of human zinc-dependent HDAC and sirtuin isoforms. We identified HDAC3 as a robust delactoylase with several-thousand-fold higher activity as compared to SIRT2, which was claimed to be the major delactoylase. Additionally, we systematically searched for enzymes, capable of removing pyruvoyl residues from lysine side chains. Using model peptides, we uncovered high depyruvoylase activity for HDAC6 and HDAC8. Interestingly, such substrates have extremely low values for both HDAC isoforms, pointing to possible functions.
Topics: Aging; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Lysine; Protein Isoforms; Repressor Proteins; Sirtuin 2; Zinc
PubMed: 35639992
DOI: 10.1021/acschembio.1c00863 -
Journal of Oncology 2022Although the effects of methylation of the Ras association domain-containing protein 1 isoform A () gene in cell-free DNA on the outcomes of patients with different... (Review)
Review
BACKGROUND
Although the effects of methylation of the Ras association domain-containing protein 1 isoform A () gene in cell-free DNA on the outcomes of patients with different types of cancer have been reported, the results are inconsistent.
OBJECTIVE
: To explore the relationships between methylation in cell-free DNA and the outcomes of cancer patients.
METHODS
The PubMed, Embase, and Web of Science databases were searched for papers related to this topic on December 8, 2021. The retrieved articles were screened by two independent researchers, following which the methodological quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Additionally, hazard ratios were calculated, and publication bias of the studies was determined using Egger's test.
RESULTS
Nine relevant publications involving a combined total of 1254 patients with different types of cancer were included in this study. The combined results of the random effects models yielded a hazard ratio of 1.73 (95% confidence interval: 1.31, 2.29; < 0.001), which suggested there was a significant association between methylation and overall survival, and patients with an methylation status had a significantly increased risk of total death. Moreover, the Egger test result suggested there was no significant publication bias among the included studies.
CONCLUSIONS
The methylation of in cell-free DNA in cancer patients was observably associated with an increased risk of poor overall survival.
PubMed: 35528240
DOI: 10.1155/2022/3458420 -
Neuroscience and Biobehavioral Reviews Jun 2022Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD. (Review)
Review
BACKGROUND
Brain co-morbidities in DMD are well-documented, less is known about the cognitive, behavioral and psychosocial functioning of patients with BMD.
METHODS
The systematic review was carried out on two databases (Pubmed and Scopus) according to the PRISMA guidelines. We included all research articles specific to BMD written after 1995.
RESULTS
Studies examining neuropsychological and neurobehavioral functioning in BMD are few and have several methods limitations. BMD population is characterized by high rates of cognitive impairment, with specific involvement of different cognitive areas. Unlike DMD, verbal skills are better preserved. Neurodevelopmental and emotional/behavioral disorders have great importance in BMD, due to their high prevalence. Lack of Dp140 or Dp71 can cause intellectual disability, these isoforms are probably responsible for the other brain-related comorbidities as well.
DISCUSSION
The results suggest that cognitive and neuropsychiatric comorbid symptoms may affect a significant proportion of BMD patients therefore it is important to mental health and neuropsychological screening. Finding tools for an adequate assessment is a priority in order to include brain outcome measures in clinical trials.
Topics: Brain; Cognition; Dystrophin; Humans; Muscular Dystrophy, Duchenne; Protein Isoforms
PubMed: 35367224
DOI: 10.1016/j.neubiorev.2022.104648 -
Frontiers in Aging Neuroscience 2022Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive...
BACKGROUND
Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive diagnostic tests to detect biomarkers in the earliest and asymptomatic stages of the disease. Blood-based biomarkers are predicted to have the most impact for use as a screening tool and predict the onset of AD, especially in LMICs. Furthermore, it has been suggested that panels of markers may perform better than single protein candidates.
METHODS
Medline/Pubmed was searched to identify current relevant studies published from January 2016 to December 2020. We included all full-text articles examining blood-based biomarkers as a set of protein markers or panels to aid in AD's early diagnosis, prognosis, and characterization.
RESULTS
Seventy-six articles met the inclusion criteria for systematic review. Majority of the studies reported plasma and serum as the main source for biomarker determination in blood. Protein-based biomarker panels were reported to aid in AD diagnosis and prognosis with better accuracy than individual biomarkers. Conventional (amyloid-beta and tau) and neuroinflammatory biomarkers, such as amyloid beta-42, amyloid beta-40, total tau, phosphorylated tau-181, and other tau isoforms, were the most represented. We found the combination of amyloid beta-42/amyloid beta-40 ratio and APOEε4 status to be most represented with high accuracy for predicting amyloid beta-positron emission tomography status.
CONCLUSION
Assessment of Alzheimer's disease biomarkers in blood as a non-invasive and cost-effective alternative will potentially contribute to early diagnosis and improvement of therapeutic interventions. Given the heterogeneous nature of AD, combination of markers seems to perform better in the diagnosis and prognosis of the disease than individual biomarkers.
PubMed: 35360215
DOI: 10.3389/fnagi.2022.683689