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Progress in Lipid Research Oct 2016Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby... (Review)
Review
Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby affect cardiovascular health. We aimed to systematically review studies investigating the association between epigenetic marks and plasma concentrations of triacylglycerol, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Six medical databases were searched until September 3rd 2015, reference lists were screened, and experts in the field were contacted. Of the 757 identified references, 31 articles reporting on 23 unique studies met all inclusion criteria. These studies included data on 8027 unique participants. Overall, no consistent associations were observed between global DNA methylation and blood lipids. Candidate gene and epigenome-wide association studies reported epigenetic regulation of several genes to be related with blood lipids, of which results for ABCG1, CPT1A, TNNT1, MIR33B, SREBF1, and TNIP were replicated. To date, no studies have been performed on histone modification in relation to blood lipids. To conclude, promising results have been reported in the field of epigenetics and dyslipidaemia, however, further rigorous studies are needed to expand our understanding on the role of epigenetics in regulating human's blood lipid levels and its effects on health and disease.
Topics: ATP Binding Cassette Transporter 1; Carrier Proteins; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; DNA Methylation; Dyslipidemias; Epigenomics; Humans; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins; Niemann-Pick C1 Protein; Triglycerides
PubMed: 27746199
DOI: 10.1016/j.plipres.2016.10.002 -
The Japanese Dental Science Review Dec 2023Mutations in are the most common genetic cause of tooth agenesis (TA). The aim of this study was to systematically review the profiles of the TA and variants and... (Review)
Review
Mutations in are the most common genetic cause of tooth agenesis (TA). The aim of this study was to systematically review the profiles of the TA and variants and establish their genotype-phenotype correlation. Forty articles were eligible for 178 patients and 61 mutations (26 in frame and 32 null mutations). mutations predominantly affected molars, mostly the second molar, and the mandibular first premolar was the least affected. More missing teeth were found in the maxilla than the mandible, and with null mutations than in-frame mutations. The number of missing teeth was correlated with the locations of the in-frame mutations with the C-terminus mutations demonstrating the fewest missing teeth. The null mutation location did not influence the number of missing teeth. Null mutations in all locations predominantly affected molars. For the in-frame mutations, a missing second molar was commonly associated with mutations in the highly conserved paired DNA-binding domain, particularly the linking peptide (100% prevalence). In contrast, C-terminus mutations were rarely associated with missing second molars and anterior teeth, but were commonly related to an absent second premolar. These finding indicate that the mutation type and position contribute to different degrees of loss of function that further differentially influences the manifestations of TA. This study provides novel information on the correlation of the genotype-phenotype, aiding in the genetic counseling for TA.
PubMed: 37159578
DOI: 10.1016/j.jdsr.2023.04.001 -
Amino Acids Sep 2018Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups... (Review)
Review
Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups of DNA, lipids and proteins. Carnosine is a naturally occurring dipeptide with antioxidant activity, which inhibits protein carbonylation and glycoxidation. This systematic review searched international sources for all published and unpublished original research in English from any year up to the end of April 2018. An electronic search of PubMed, Scopus and Google Scholar was conducted. 187 articles were initially found and 133 articles were selected after excluding duplicated data. Review articles, studies based on the components of carnosine and studies that were about the effects of carnosine on AGEs-induced changes were excluded. In total, 36 studies met the inclusion criteria. This included 19 in vitro studies, 15 animal studies and two human studies. All but two of the studies indicated that carnosine can prevent the formation of AGEs. The findings of this review indicating that carnosine has anti-glycating properties, and may hinder the formation of protein carbonyls and the cross-links induced by reduced sugars; however, there were few human studies. The mechanism by which carnosine prevents the formation of AGEs needs further investigation.
Topics: Animals; Carnosine; Glycation End Products, Advanced; Humans; Protein Carbonylation; Proteins
PubMed: 29858687
DOI: 10.1007/s00726-018-2592-9 -
Cancers Aug 2020Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median... (Review)
Review
Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional structures of single-stranded nucleic acids (RNA or DNA), identified by an in vitro process, named systematic evolution of ligands by exponential enrichment (SELEX), starting from a partially random oligonucleotide library. They bind to a molecular target with high affinity and specificity and can be easily modified to optimize binding affinity and selectivity. Thanks to their properties (low immunogenicity and toxicity, long stability, and low production variability), a large number of aptamers have been selected against GBM biomarkers and provide specific imaging agents and therapeutics to improve the diagnosis and treatment of GBM. However, the use of aptamers in GBM diagnosis and treatment still represents an underdeveloped topic, mainly due to limited literature in the research world. On these bases, we performed a systematic review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for GBM diagnosis and treatment. Thirty-eight studies from 2000 were included and investigated. Seventeen involved the use of aptamers for GBM diagnosis and 21 for GBM therapy. Our findings showed that a number of DNA and RNA aptamers are promising diagnostic and therapeutic tools for GBM management.
PubMed: 32764266
DOI: 10.3390/cancers12082173 -
Critical Reviews in Food Science and... Dec 2023NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family,... (Review)
Review
NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both and models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP.
PubMed: 38153262
DOI: 10.1080/10408398.2023.2294164 -
Heart Rhythm Apr 2023Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia... (Meta-Analysis)
Meta-Analysis Review
Fetal long QT syndrome (LQTS) may present with sinus bradycardia, functional 2:1 atrioventricular block (AVB), and ventricular arrhythmias (ventricular tachycardia [VT]/torsades de pointes [TdP]) and lead to fetal or postnatal death. We performed a systematic review and individual participant data meta-analysis of 83 studies reporting outcomes of 265 fetuses for which suspected LQTS was confirmed postnatally and determined risk of adverse perinatal and postnatal outcomes using logistic and stepwise logistic regression. A longer fetal QTc was more predictive of death than any other antenatal factor (receiver operating characteristic [ROC] area under the curve [AUC] 0.85; 95% confidence interval [CI] 0.66-1.00). Risk of death was significantly increased with fetal QTc >600 ms. Neither fetal heart rate nor heart rate z-score predicted death (ROC AUC 0.51; 95% CI 0.31-0.71; and ROC AUC 0.59; 95% CI 0.37-0.80, respectively). The combination of antenatal VT/TdP or functional 2:1 AVB and lack of family history of LQTS was also highly predictive of death (ROC AUC 0.82; 95% CI 0.76-0.88). Our data provide clinical screening tools to enable prediction and intervention for fetuses with LQTS at risk of death.
Topics: Humans; Pregnancy; Female; Electrocardiography; Long QT Syndrome; Torsades de Pointes; Heart Rate, Fetal; Atrioventricular Block; Fetus; DNA-Binding Proteins
PubMed: 36566891
DOI: 10.1016/j.hrthm.2022.12.026 -
Oral Surgery, Oral Medicine, Oral... Sep 2022This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.
STUDY DESIGN
An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis.
RESULTS
HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality.
CONCLUSION
The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.
Topics: Child; DNA-Binding Proteins; Humans; Mutation; Rhabdomyosarcoma; Transcription Factors
PubMed: 35840496
DOI: 10.1016/j.oooo.2021.12.128 -
BMC Genomics Aug 2022The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including...
BACKGROUND
The histidine metabolism and transport (his) genes are controlled by a variety of RNA-dependent regulatory systems among diverse taxonomic groups of bacteria including T-box riboswitches in Firmicutes and Actinobacteria and RNA attenuators in Proteobacteria. Using a comparative genomic approach, we previously identified a novel DNA-binding transcription factor (named HisR) that controls the histidine metabolism genes in diverse Gram-positive bacteria from the Firmicutes phylum.
RESULTS
Here we report the identification of HisR-binding sites within the regulatory regions of the histidine metabolism and transport genes in 395 genomes representing the Bacilli, Clostridia, Negativicutes, and Tissierellia classes of Firmicutes, as well as in 97 other HisR-encoding genomes from the Actinobacteria, Proteobacteria, and Synergistetes phyla. HisR belongs to the TrpR family of transcription factors, and their predicted DNA binding motifs have a similar 20-bp palindromic structure but distinct lineage-specific consensus sequences. The predicted HisR-binding motif was validated in vitro using DNA binding assays with purified protein from the human gut bacterium Ruminococcus gnavus. To fill a knowledge gap in the regulation of histidine metabolism genes in Firmicutes genomes that lack a hisR repressor gene, we systematically searched their upstream regions for potential RNA regulatory elements. As result, we identified 158 T-box riboswitches preceding the histidine biosynthesis and/or transport genes in 129 Firmicutes genomes. Finally, novel candidate RNA attenuators were identified upstream of the histidine biosynthesis operons in six species from the Bacillus cereus group, as well as in five Eubacteriales and six Erysipelotrichales species.
CONCLUSIONS
The obtained distribution of the HisR transcription factor and two RNA-mediated regulatory mechanisms for histidine metabolism genes across over 600 species of Firmicutes is discussed from functional and evolutionary points of view.
Topics: Actinobacteria; Bacteria; DNA; Gene Expression Regulation, Bacterial; Gram-Positive Bacteria; Histidine; Humans; Phylogeny; Riboswitch; Transcription Factors
PubMed: 36008760
DOI: 10.1186/s12864-022-08796-y -
International Journal of Molecular... Nov 2022Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT)... (Review)
Review
Aldehydes, particularly acetaldehyde, are carcinogenic molecules and their concentrations in foodstuffs should be controlled to avoid upper aerodigestive tract (UADT) and liver cancers. Highly reactive, acetaldehyde forms DNA and protein adducts, impairing physiological functions and leading to the development of pathological conditions. The consumption of aged beer, outside of the ethanol metabolism, exposes habitual drinkers to this carcinogen, whose concentrations can be over-increased due to post-brewing chemical and biochemical reactions. Storage-related changes are a challenge faced by the brewing industry, impacting volatile compound formation and triggering flavor instability. Aldehydes are among the volatile compounds formed during beer aging, recognized as off-flavor compounds. To track and understand aldehyde formation through multiple pathways during beer storage, consequent changes in flavor but particularly quality losses and harmful compound formation, this systematic review reunited data on volatile compound profiles through gas chromatography analyses from 2011 to 2021. Conditions to avoid flavor instability and successful methods for reducing beer staling, and consequent acetaldehyde accumulation, were raised by exploring the dynamic conversion between free and bound-state aldehydes. Future research should focus on implementing sensory analyses to investigate whether adding aldehyde-binding agents, e.g., cysteine and bisulfite, would contribute to consumer acceptance, restore beer flavor, and minimize acetaldehyde-related health damage.
Topics: Humans; Aged; Acetaldehyde; Aldehydes; Beer; Carcinogens; Carcinogenesis
PubMed: 36430619
DOI: 10.3390/ijms232214147 -
Epigenomics Sep 2017Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically... (Meta-Analysis)
Meta-Analysis Review
AIM
Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically review and evaluate the literature on prognostic DNA methylation markers for RCC.
MATERIALS & METHODS
We conducted an exhaustive search of PubMed, EMBASE and MEDLINE up to April 2017 and identified 49 publications. Studies were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, assessed for their reporting quality using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) criteria, and were graded to determine the level of evidence (LOE) for each biomarker.
RESULTS
We identified promoter methylation of BNC1, SCUBE3, GATA5, SFRP1, GREM1, RASSF1A, PCDH8, LAD1 and NEFH as promising prognostic markers. Extensive methodological heterogeneity across the included studies was observed, which hampers comparability and reproducibility of results, providing a possible explanation why these biomarkers do not reach the clinic.
CONCLUSION
Potential prognostic methylation markers for RCC have been identified, but they require further validation in prospective studies to determine their true clinical value.
Topics: Biomarkers, Tumor; Cadherins; Calcium-Binding Proteins; Carcinoma, Renal Cell; DNA Methylation; DNA-Binding Proteins; GATA5 Transcription Factor; Humans; Intercellular Signaling Peptides and Proteins; Kidney Neoplasms; Membrane Proteins; Neurofilament Proteins; Promoter Regions, Genetic; Protocadherins; Transcription Factors; Tumor Suppressor Proteins
PubMed: 28803494
DOI: 10.2217/epi-2017-0040