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Omics : a Journal of Integrative Biology 2011Hepatocellular carcinoma (HCC) has been a major clinical challenge due to low early diagnosis rate and poor prognosis. The aim of this systematic review was to identify... (Review)
Review
Hepatocellular carcinoma (HCC) has been a major clinical challenge due to low early diagnosis rate and poor prognosis. The aim of this systematic review was to identify differentially expressed proteins as potential high-confidence biomarkers for HCC, by validating data on differentially expressed proteins reported by studies on HCC tissues. In our studies, objectives, search strategy, study selection criteria, data elements, methods for extraction, and methods for assessing study quality were defined. Published studies that compared the protein expression profiles of HCC with those of noncancer tissues were included in the review. Furthermore, a protein ranking system was used to assess the number of comparisons in agreement. Monte Carlo simulation was used to assess the overlap significance. A total of 16 proteomic studies were eligible for the systematic review in our study, which reported 1283 differentially expressed proteins in HCC (526 upregulated, 744 downregulated). Of these proteins, 27 proteins were identified as differentially expressed proteins with consistent directions of change in at least three studies; four were upregulated, and 23 downregulated. One upregulated protein, heat-shock 70-kDa protein, and four downregulated proteins, fructose-1,6-bisphosphatase 1, formiminotransferase cyclodeaminase, alcohol dehydrogenase, and fructose-bisphosphate aldolase B were identified as potential biomarkers for HCC. In addition, nine other differentially expressed proteins were reported, but with inconsistent directions for the changes of the differential expression. The amount of overlap was highly significant. Therefore, five candidate proteins were defined as potential biomarkers for HCC, which may have diagnostic, prognostic and therapeutic significance.
Topics: Carcinoma, Hepatocellular; Down-Regulation; Humans; Liver Neoplasms; Monte Carlo Method; Neoplasm Proteins; Proteomics; Up-Regulation
PubMed: 20726783
DOI: 10.1089/omi.2010.0061 -
Advances in Experimental Medicine and... 2019Cerebral stroke is one of the leading causes of mortality and disability worldwide. The prevalence of cerebral stroke is the result of the synergistic effect of genetic...
Cerebral stroke is one of the leading causes of mortality and disability worldwide. The prevalence of cerebral stroke is the result of the synergistic effect of genetic susceptibility and numerous vascular risk factors, including hypertension, diabetes, excessive alcohol intake, obesity, and dyslipidemia. Mitochondrial aldehyde dehydrogenase (ALDH2) is a vital enzyme metabolizing various acetaldehyde and toxic aldehydes. The ALDH2 enzymatic activity is severely decreased in the individuals with ALDH2*2 gene mutation, especially in East Asians. Increasing epidemiological surveys have revealed that ALDH2 genetic polymorphism is closely associated with the increasing incidence of cardiovascular risk factors and cerebral stroke. Evidence from experimental studies has also suggested that ALDH2 facilitates the clearance of reactive aldehydes and reduces the size of cerebral infarct. Therefore, targeting ALDH2 may represent a promising avenue for protection against stroke injury. This review will mainly focus on clinical and epidemiological evidence and the underlying molecular mechanisms involved in the protective effect of ALDH2 in stroke-related injury.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Stroke
PubMed: 31368105
DOI: 10.1007/978-981-13-6260-6_11 -
Journal of Toxicology. Clinical... 2003Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in... (Review)
Review
INTRODUCTION
Treatment thresholds for methanol poisoning are based on case reports and published opinion. Most guidelines recommend treatment for a methanol level > or = 20 mg/dL in a nonacidotic patient. No supportive data have been offered nor has the time of the exposure been addressed. For instance, no distinction has been drawn between a methanol level drawn 1 hr vs. 24 hr from ingestion. We analyzed all published cases of methanol poisoning to determine the applicability of the 20 mg/dL threshold in a nonacidotic patient, specifically those arriving early for care (within 6 hr) with a peak or near-peak blood methanol concentration.
METHODS
Using predefined search criteria, a systematic review of the world literature was performed using MEDLINE and EMBASE. In addition, each article's references were hand searched for pre-1966 articles, as were fatality abstracts from all U.S. poison centers. Human cases were included if they reported a known time of a single methanol exposure, acid-base data, blood methanol, and blood ethanol (if not acidotic).
RESULTS
Dating to 1879, 372 articles in 18 languages were abstracted using a standard format; 329 articles (2433 patients) involved methanol poisoning, and 70 articles (173 patients) met inclusion criteria. Only 22 of these patients presented for care within 6hr of ingestion with an early methanol level. All but 1 patient was treated with an inhibitor of alcohol dehydrogenase (ADH). A clear acidosis developed only with a methanol level > or = 126 mg/dL. The patient that did not receive an ADH inhibitor was an infant with an elevated early methanol level (46 mg/dL) that was given folate alone and never became acidotic. Intra and inter-rater reliability were 0.95.
CONCLUSIONS
Nearly all reports of methanol poisoning involve acidotic patients far removed from ingestion. The small amount of data regarding patients arriving early show that 126 mg/dL is the lowest early blood methanol level ever clearly associated with acidosis. Contrary to conventional teaching, there are case reports of acidosis after only a few hours of ingestion. The data are insufficient to apply 20 mg/dL as a treatment threshold in a nonacidotic patient arriving early for care. Prospective studies are necessary to determine if such patients may be managed without antidotal therapy or dialysis.
Topics: Acidosis; Adolescent; Adult; Antidotes; Bicarbonates; Child, Preschool; Dose-Response Relationship, Drug; Female; Fomepizole; Humans; Male; Methanol; Middle Aged; Pyrazoles; Treatment Outcome
PubMed: 14677789
DOI: 10.1081/clt-120025344 -
Annals of Human Genetics Jul 2022The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)-CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671-with CH were studied previously, but the results were inconsistent.
METHODS
Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software.
RESULTS
Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on CLOCK rs1801260, five on ADH4 rs1800759, and three on ADH4 rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the CLOCK gene, rs1800759 and rs1126671 in the ADH4 gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95-1.28; p = 0.19; rs1800759: OR 1.06, 95% CI: 0.93-1.22; p = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92-1.28; p = 0.32).
CONCLUSION
We found no significant associations between the three SNPs (rs1801260 in the CLOCK gene and rs1800759 and rs1126671 in the ADH4 gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.
Topics: Alcohol Dehydrogenase; CLOCK Proteins; Case-Control Studies; Cluster Headache; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide
PubMed: 35437765
DOI: 10.1111/ahg.12467 -
Current Pharmaceutical Design 2010Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the... (Review)
Review
Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-HT reuptake inhibitors (e.g. fluoxetine), 5-HT(1) receptor agonists (e.g. buspirone), 5-HT(2) receptor antagonists (e.g. ritanserin), 5-HT(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies. However, further randomized studies with larger samples are warranted to establish their efficacy and safety profiles in the treatment of alcohol dependence.
Topics: Adult; Alcohol Deterrents; Alcoholism; Animals; Drug Design; Ethanol; Gene Expression Regulation; Humans; Oligonucleotide Array Sequence Analysis; Polymorphism, Genetic; Rats; Signal Transduction
PubMed: 20184550
DOI: 10.2174/138161210791034030 -
Addiction (Abingdon, England) Sep 2022Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of...
Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies.
BACKGROUND AND AIMS
Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome-wide findings is lacking for substance use. Here, we combined all the genome-wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs.
METHODS
Systemic literature search for genome-wide association (GWAS) and RNA-seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case-control or case/cohort samples. RNA-seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P ≤ 1 × 10 ) in GWAS and reported as significant in RNA-seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database.
RESULTS
Total SUBD-related 2910 genes were extracted from 75 GWAS studies (2 773 889 participants) and 17 RNA-seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2, GRIN2B, PLXDC2 and PKNOX2), four shared pathways [two Gene Ontology (GO) terms of 'modulation of chemical synaptic transmission', 'regulation of trans-synaptic signaling', two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of 'dopaminergic synapse', 'cocaine addiction'] were identified (significantly higher than random, P < 1 × 10 ). The top shared KEGG pathways (Benjamini-Hochberg-corrected P-value < 0.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were 'Epstein-Barr virus infection', 'protein processing in endoplasmic reticulum' and 'neuroactive ligand-receptor interaction', respectively. We also identified substance-specific genetic factors: i.e. ADH1B and ALDH2 were unique for AUBD, while CHRNA3 and CHRNA4 were unique for NUBD.
CONCLUSIONS
This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome-wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Animals; Cocaine; Epstein-Barr Virus Infections; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Herpesvirus 4, Human; Humans; Nicotine; Polymorphism, Single Nucleotide; Substance-Related Disorders; Tobacco Use Disorder; Transcriptome
PubMed: 35491750
DOI: 10.1111/add.15908 -
Critical Care Medicine Feb 2015Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration... (Review)
Review
OBJECTIVE
Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning.
DESIGN AND METHODS
Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus.
RESULTS
Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤ 7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage.
CONCLUSION
Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.
Topics: Acidosis; Antidotes; Biomarkers; Humans; Methanol; Practice Guidelines as Topic; Renal Dialysis; Severity of Illness Index
PubMed: 25493973
DOI: 10.1097/CCM.0000000000000708 -
Neuroscience and Biobehavioral Reviews Nov 2020The identification of bipolar disorder (BD) type II patients has both treatment and prognostic implications. Better understanding of its underlying genetics may yield... (Review)
Review
BACKGROUND
The identification of bipolar disorder (BD) type II patients has both treatment and prognostic implications. Better understanding of its underlying genetics may yield useful diagnostic tools.
METHODS
A systematic review on BDII genetics was done using articles published in 2009-2019, following PRISMA recommendations.
RESULTS
The most studied polymorphism was BDNF Val66Met with several gene-gene interactions within the dopaminergic system. Associations were reported within the monoaminergic systems (DRD3, ADH1B and SLC6A4), calcium (CACNB2 and CACNG2) and cAMP (PDE1DA, PDE4B and DISC1) signal transduction pathways and the immune system (TNFα, IFNδ and IL-10). Chromosomes 2, 3 and 10 were associated with BDII and polygenic risk scores distinguished between BD subtypes and with major depressive disorder.
CONCLUSIONS
Research on BDII stems from BDI findings, however with a stronger contribution of gene-gene interactions and low-effect alleles on known neuroplasticity and monoaminergic system genes. Genome studies point to transdiagnostic backgrounds, with wider associations across bipolar spectrum disorders. Findings able to accurately differentiate BDII remain elusive, dependent on better phenotypic characterization and new research methods.
Topics: Alcohol Dehydrogenase; Bipolar Disorder; Depressive Disorder, Major; Humans; Polymorphism, Single Nucleotide; Serotonin Plasma Membrane Transport Proteins
PubMed: 32755611
DOI: 10.1016/j.neubiorev.2020.07.033 -
Alcoholism, Clinical and Experimental... Feb 2021Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk.
METHODS
A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power.
RESULTS
Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I = 81.9%).
CONCLUSIONS
In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Asian People; Case-Control Studies; Asia, Eastern; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Polymorphism, Single Nucleotide
PubMed: 33283290
DOI: 10.1111/acer.14527 -
Bioscience Reports Apr 2019Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in... (Meta-Analysis)
Meta-Analysis
Alcohol consumption has been established to be a major factor in the development and progress of cancer. Genetic polymorphisms of alcohol-metabolism genes result in differences between individuals in exposure to acetaldehyde, leading to possible carcinogenic effects. Arg47His (rs1229984 G > A) in have been frequently studied for its potential effect on carcinogenesis. However, the findings are as yet inconclusive. To gain a more precise estimate of this potential association, we conducted a meta-analysis including 66 studies from 64 articles with 31999 cases and 50964 controls. The pooled results indicated that Arg47His polymorphism is significantly associated with the decreased risk of overall cancer (homozygous model, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.49-0.77; heterozygous model, OR = 0.71, 95% CI = 0.60-0.84; recessive model, OR = 0.83, 95% CI = 0.76-0.91; dominant model, OR = 0.62, 95% CI = 0.53-0.72; and allele comparison, OR = 0.82, 95% CI = 0.75-0.89). Stratified analysis by cancer type and ethnicity showed that a decreased risk was associated with esophageal cancer and head and neck cancer amongst Asians. In conclusion, our meta-analysis suggested that Arg47His polymorphism was significantly associated with decreased overall cancer risk. These findings need further validation in large multicenter investigations.
Topics: Alcohol Dehydrogenase; Carcinogenesis; Esophageal Neoplasms; Head and Neck Neoplasms; Models, Genetic; Neoplasm Proteins; Neoplasms; Polymorphism, Genetic
PubMed: 30872408
DOI: 10.1042/BSR20181915