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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 -
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 -
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 -
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 -
Modern Pathology : An Official Journal... Dec 2022Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been... (Meta-Analysis)
Meta-Analysis
Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.
Topics: Humans; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1; MutS Homolog 2 Protein; DNA-Binding Proteins; Colorectal Neoplasms; DNA Mismatch Repair; Biomarkers, Tumor; Algorithms
PubMed: 36104536
DOI: 10.1038/s41379-022-01149-w -
Journal of Clinical Medicine Aug 2022: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate... (Review)
Review
: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. . To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I = 89%, = 0.03). In contrast, CCCTC-binding factor 6 (CTCF6), (), (), and () were not differently methylated in ART vs. SC offspring. : The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.
PubMed: 36078985
DOI: 10.3390/jcm11175056 -
Frontiers in Genetics 2022Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease,...
Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease, pancreatitis and/or multiple organ failures before diagnosis. Better guidelines for the recognition and early diagnosis of rare dyslipidaemias are urgently required. Genomic DNA was isolated from blood samples of a Pakistani paediatric patient with hypertriglyceridemia, and from his parents and siblings. Next-generation sequencing (NGS) was performed, and an expanded dyslipidaemia panel was employed for genetic analysis. The NGS revealed the presence of a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the (glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) gene resulting in amino acid change p.Cys77Tyr (NP_835466.2). The patient was 5.5 years old at the time of genetic diagnosis. The maximal total cholesterol and triglyceride levels were measured at the age of 10 months (850.7 mg/dl, 22.0 mmol/L and 5,137 mg/dl, 58.0 mmol/L, respectively). The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the gene and clinical findings, associated with hyperlipoproteinemia. In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the gene causing hyperlipoproteinemia (type 1D). In cases of severe elevations of plasma cholesterol and/or triglycerides genetic testing for rare dyslipidaemias should be performed as soon as possible for optimal therapy and patient management.
PubMed: 36051701
DOI: 10.3389/fgene.2022.983283 -
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 -
Acta Neuropathologica Communications Aug 2022Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of... (Review)
Review
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of hyperphosphorylated tau (p-tau) in the depths of cortical sulci. CTE can only be diagnosed postmortem and the cellular mechanisms of disease causation remain to be elucidated. Understanding the full scope of the pathological changes currently identified in CTE is necessary to identify areas requiring further research. This systematic review summarises the current literature on CTE pathology from postmortem human tissue histology studies published until 31 December 2021. Publications were included if they quantitively or qualitatively compared postmortem human tissue pathology in CTE to neuropathologically normal cases or other neurodegenerative diseases such as Alzheimer's disease (AD). Pathological entities investigated included p-tau, beta-amyloid, TDP-43, Lewy bodies, astrogliosis, microgliosis, axonopathy, vascular dysfunction, and cell stress. Of these pathologies, p-tau was the most frequently investigated, with limited reports on other pathological features such as vascular dysfunction, astrogliosis, and microgliosis. Consistent increases in p-tau, TDP-43, microgliosis, axonopathy, and cell stress were reported in CTE cases compared to neuropathologically normal cases. However, there was no clear consensus on how these pathologies compared to AD. The CTE cases used for these studies were predominantly from the VA-BU-CLF brain bank, with American football and boxing as the most frequent sources of repetitive head injury exposure. Overall, this systematic review highlights gaps in the literature and proposes three priorities for future research including: 1. The need for studies of CTE cases with more diverse head injury exposure profiles to understand the consistency of pathology changes between different populations. 2. The need for more studies that compare CTE with normal ageing and AD to further clarify the pathological signature of CTE for diagnostic purposes and to understand the disease process. 3. Further research on non-aggregate pathologies in CTE, such as vascular dysfunction and neuroinflammation. These are some of the least investigated features of CTE pathology despite being implicated in the acute phase response following traumatic head injury.
Topics: Alzheimer Disease; Chronic Traumatic Encephalopathy; DNA-Binding Proteins; Gliosis; Humans; Neurodegenerative Diseases; Neuropathology; tau Proteins
PubMed: 35933388
DOI: 10.1186/s40478-022-01413-9 -
Neuropathology and Applied Neurobiology Dec 2022Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral... (Review)
Review
Over the past decade, considerable efforts have been made to accelerate pathophysiological understanding of fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) with brain banks at the forefront. In addition to exploratory disease mechanisms, brain banks have aided our understanding with regard to clinical diagnosis, genetics and cell biology. Across neurodegenerative disorders, the impact of brain tissue in ALS research has yet to be quantified. This review aims to outline (i) how postmortem tissues from brain banks have influenced our understanding of ALS over the last 15 years, (ii) correlate the location of dedicated brain banks with the geographical prevalence of ALS, (iii) identify the frequency of features reported from postmortem studies and (iv) propose common reporting standards for materials obtained from dedicated brain banks. A systematic review was conducted using PubMed and Web of Science databases using key words. From a total of 1439 articles, 73 articles were included in the final review, following PRISMA guidelines. Following a thematic analysis, articles were categorised into five themes; clinico-pathological (13), genetic (20), transactive response DNA binding protein 43 (TDP-43) pathology (12), non-TDP-43 neuronal pathology (nine) and extraneuronal pathology (19). Research primarily focused on the genetics of ALS, followed by protein pathology. About 63% of the brain banks were in the United States of America and United Kingdom. The location of brain banks overall aligned with the incidence of ALS worldwide with 88% of brain banks situated in Europe and North America. An overwhelming lack of consistency in reporting and replicability was observed, strengthening the need for a standardised reporting system. Overall, postmortem material from brain banks generated substantial new knowledge in areas of genetics and proteomics and supports their ongoing role as an important research tool.
Topics: Humans; Amyotrophic Lateral Sclerosis; Knowledge Discovery; Brain; Neurons; United Kingdom
PubMed: 35921237
DOI: 10.1111/nan.12845