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Molecular Genetics & Genomic Medicine Sep 2020Dishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant...
BACKGROUND
Dishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now.
METHODS
The expression of DVL isoforms was assessed using the Oncomine, HCCDB and UALCAN databases. The prognostic roles of DVLs were further evaluated using the GEPIA database. The relationship between the expression of DVLs and immune infiltration of HCC was investigated using the Timer and ImmuCellAI tools. Furthermore, protein-protein interaction (PPI) networks were built and enrichment analyses were conducted.
RESULTS
We found that the expression levels of DVL2 (OMIM accession number: 602151) and DVL3 (OMIM accession number: 601368) were upregulated in HCC tissues as revealed by the Oncomine and HCCDB databases. Additionally, the expression of DVLs tended to be associated with advanced clinical features in the UALCAN database. Prognostic analysis revealed that the expression levels of DVL1 (OMIM accession number: 601365) and DVL3 were remarkably associated with a poor prognosis in HCC patients. The results also revealed that the DVL expression level was correlated with the infiltration levels of multiple immune cells. By constructing the PPI network and enrichment analyses, the DVL1-3 gene was identified to interact with 20 key genes and participate in several pathways.
CONCLUSION
In summary, DVL2 and DVL3 are highly expressed in HCC, and DVL1 and DVL3 are related to a poor prognosis, which might be used as candidate targets for targeted therapy and reliable prognostic biomarkers in HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Databases, Genetic; Dishevelled Proteins; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Up-Regulation
PubMed: 32588988
DOI: 10.1002/mgg3.1384 -
Clinical Chemistry and Laboratory... Aug 2018The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status.
BACKGROUND
The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status.
CONTENTS
An advanced search was conducted using MeSH terms related to salivary biomarkers and CVD, and entered into the PubMed, Web of Science, and Google Scholar search databases. Four hundred and thirty-three records were narrowed to 22 accepted articles. Included titles were assessed for quality using the Newcastle-Ottawa scale, and ranked into categories of low, moderate, or high.
SUMMARY
A total of 40 salivary biomarkers were analyzed among accepted articles. The most studied markers were salivary creatine kinase isoform MB, C-reactive protein (CRP), matrix metalloproteinase-9, troponin I, myeloperoxidase, myoglobin, and brain natriuretic peptide. Salivary CRP provided the most consistent trends. Statistically significant increases of salivary CRP were present with CVD in every study that analyzed it. The remaining six markers demonstrated varying patterns.
OUTLOOK
Existing studies provide insufficient data to draw definitive conclusions. Current research shows that there is an association between some salivary biomarkers and CVD, but the details of existing studies are conflicting. Despite inconclusive results, the diagnostic potential of saliva shows promise as a non-invasive means of cardiovascular risk assessment.
Topics: Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Matrix Metalloproteinase 9; Saliva
PubMed: 29630504
DOI: 10.1515/cclm-2017-1018 -
American Journal of Reproductive... Dec 2018Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is...
Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is unknown. Therefore, we conducted a systematic review of literature on p38 MAPK expression, activation, and function in reproductive tissues throughout pregnancy and parturition, published between January 1980 and August 2017, using four electronic databases (Web of Science, PubMed, Medline, and CoCHRANE). We identified 418 reports; 108 were selected for full-text evaluation and 74 were included in final review. p38 MAPK was investigated using feto-maternal primary or immortalized cells, tissue explants, and animal models. Western blot was most commonly used to report phosphorylated (active) p38 MAPK. Human placenta (27), chorioamniotic membranes (14), myometrium (13), decidua (8), and cervix (1) were the studied tissues. p38 MAPK's functions were tissue and gestational age dependent. Isoform specificity was hardly reported. p38 MAPK activity was induced by ROS or proinflammatory cytokines to promote cell signaling linked to cell fate, primed uterus, ripened cervix, and proinflammatory cytokine/chemokine production. In 35 years, reports on p38 MAPK's role during pregnancy and parturition are scarce and current literature is insufficient to provide a comprehensive description of p38 MAPK's mechanistic role during pregnancy and parturition.
Topics: Animals; Disease Models, Animal; Female; Gene Expression Regulation; Genitalia, Female; Humans; Inflammation; Oxidative Stress; Parturition; Pregnancy; Reproduction; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 30178469
DOI: 10.1111/aji.13047 -
Genetics in Medicine : Official Journal... Mar 2017In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-analysis of existing data.
METHODS
Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects.
CONCLUSIONS
The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.Genet Med 19 3, 275-282.
Topics: Disease Progression; Enzyme Replacement Therapy; Fabry Disease; Female; Glomerular Filtration Rate; Glycolipids; Humans; Isoenzymes; Male; Recombinant Proteins; Sphingolipids; Treatment Outcome; alpha-Galactosidase
PubMed: 27608175
DOI: 10.1038/gim.2016.117 -
Medicine Sep 2015The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent... (Meta-Analysis)
Meta-Analysis Review
The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis. PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed. A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898-2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595-2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675-1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667-3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566-1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206-3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629-3.407, P = 0.000). The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.
Topics: Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Neoplasms; Prognosis; Protein Isoforms
PubMed: 26402839
DOI: 10.1097/MD.0000000000001646 -
Prostate Cancer and Prostatic Diseases Sep 2020Approximately 10-30% of men with mCRPC will test positive for AR-V7 using one of two analytically and clinically validated circulating tumor cell (CTC)-based assays....
BACKGROUND
Approximately 10-30% of men with mCRPC will test positive for AR-V7 using one of two analytically and clinically validated circulating tumor cell (CTC)-based assays. These men have poor outcomes with approved AR-targeting therapies but may retain sensitivity to chemotherapy. Here, we discuss the clinical implications of testing and strategies that may benefit AR splice variant (AR-V)-positive men and discuss whether such variants are passengers or drivers of aggressive clinical behavior.
METHODS
We conducted a systemic review of the literature, covering updates since our 2016 review on androgen receptor variants in mCRPC, outcomes, and existing and novel approaches to therapy. We provide an expert opinion about management strategies for AR-V7-positive men and key unanswered research questions.
RESULTS
AR-V7-positive men, defined by Epic nuclear protein detection or the modified AdnaTest mRNA detection in CTCs, identify a subset of men with mCRPC that have a low probability of response to AR-targeting therapy with short progression-free and overall survival in multivariable analyses. AR-variants do not exist in isolation, but rather in the context of a complex, heterogeneous, and evolving mCRPC genome and phenotype as well as patient-specific clinical heterogeneity, and multiple mechanisms of resistance likely exist in patients regardless of AR-V7 detection. Efforts to develop broader resistance assays are needed, and effective treatment strategies beyond taxanes are needed to address the causal driver role of AR-variants and to benefit patients with AR-V-expressing prostate cancer.
CONCLUSIONS
CTC AR-V7 detection using the AdnaTest mRNA or Epic nuclear protein assays represents the first analytically and prospective clinically validated liquid biopsy assays that may inform treatment decisions in men with mCRPC, particularly after failure of first-line AR-therapy. The importance of AR-variants is likely to increase with the earlier use of AR-targeting strategies in other settings, and novel interventions for these men are needed.
Topics: Alternative Splicing; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Clinical Decision-Making; Drug Resistance, Neoplasm; Genetic Testing; Humans; Male; Precision Medicine; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Protein Isoforms; Receptors, Androgen
PubMed: 32094489
DOI: 10.1038/s41391-020-0215-5 -
Neuroscience and Biobehavioral Reviews May 2022Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate... (Review)
Review
The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight.
Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate different signal transduction pathways within PSD, involved in motor and cognitive functions, with putative implications in psychiatric disorders. Regulation of type I metabotropic glutamate receptor trafficking, modulation of calcium signaling, tuning of long-term potentiation, organization of dendritic spines' growth, as well as meta- and homeostatic plasticity control are only a few of the multiple endocellular and synaptic functions that have been linked to Homer1. Findings from preclinical studies, as well as genetic studies conducted in humans, suggest that both constitutive (Homer1b/c) and inducible (Homer1a) isoforms of Homer1 play a role in the neurobiology of several psychiatric disorders, including psychosis, mood disorders, neurodevelopmental disorders, and addiction. On this background, Homer1 has been proposed as a putative novel target in psychopharmacological treatments. The aim of this review is to summarize and systematize the growing body of evidence on Homer proteins, highlighting the role of Homer1 in the pathophysiology and therapy of mental diseases.
Topics: Carrier Proteins; Dopamine; Glutamates; Homer Scaffolding Proteins; Humans; Mental Disorders; Signal Transduction
PubMed: 35248676
DOI: 10.1016/j.neubiorev.2022.104596 -
Mutation Research. Reviews in Mutation... 2020Cleft lip and palate (CL/P) is among the most common congenital malformations and affects 1 in 700 newborns. CL/P is caused by genetic and environmental factors...
UNLABELLED
Cleft lip and palate (CL/P) is among the most common congenital malformations and affects 1 in 700 newborns. CL/P is caused by genetic and environmental factors (maternal smoking, alcohol or drug use and others). Many genes and loci were associated with cleft lip/palate but the amount of heterogeneity justifies identifying new causal genes and variants. AHRR (Aryl-Hydrocarbon Receptor Repressor) gene has recently been related to CL/P however, few functional studies analyze the genotypephenotype interaction of AHRR with CL/P. Several studies associate the molecular pathway of AHRR to CL/P which indicates this gene as a functional candidate in CL/P etiology.
METHODS
Systematic Literature Review was performed using PUBMED database with the keywords cleft lip, cleft palate, orofacial cleft, AHRR and synonyms. SLR resulted in 37 included articles.
RESULTS
AHRR is a positional and functional candidate gene for CL/P. In silico analysis detected interactions with other genes previously associated to CL/P like ARNT and CYP1A1. AHRR protein regulates cellular toxicity through TCDD mediated AHR pathway. Exposure to TCDD in animal embryos is AHR mediated and lead to cleft palate due to palate fusion failure and post fusion rupture. AHRR regulates cellular growth and differentiation, fundamental to lip and palatogenesis. AHRR decreases carcinogenesis and recently a higher tumor risk has been described in CL/P patients and families. AHRR is also a smoking biomarker due to changed methylation sites found in smokers DNA although folate intake may partially revert these methylation alterations. This corroborates the role of maternal smoking and lack of folate supplementation as risk factors for CL/P.
CONCLUSION
This research identified the importance of AHRR in dioxin response and demonstrated an example of genetic and environmental interaction, indispensable in the development of many complex diseases.
Topics: Amino Acid Motifs; Basic Helix-Loop-Helix Transcription Factors; Biomarkers; Cleft Lip; Cleft Palate; DNA Methylation; Dietary Supplements; Female; Folic Acid; Genetic Association Studies; Humans; Infant, Newborn; Male; Models, Molecular; Protein Domains; RNA Isoforms; Repressor Proteins; Risk Factors; Smoking
PubMed: 32800270
DOI: 10.1016/j.mrrev.2020.108319 -
Frontiers in Physiology 2019Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest... (Review)
Review
Endurance is not only a key factor in many sports but endurance-related variables are also associated with good health and low mortality. Twin and family studies suggest that several endurance-associated traits are ≈50% inherited. However, we still poorly understand what DNA sequence variants contribute to endurance heritability. To address this issue, we conducted a systematic review to identify genes whose experimental loss or gain-of-function increases endurance capacity in mice. We found 31 genes including two isoforms of whose manipulation increases running or swimming endurance performance by up to 1800%. Genes whose gain-of-function increases endurance are , (Pepck) (both the a and b isoforms of the protein Pgc-1α), (calcineurin) & . Genes whose loss-of-function increases endurance in mice are . Of these genes, human DNA sequence variants of , , , , , , , , and are also associated with endurance capacity and/or VOmax trainability suggesting evolutionary conservation between mice and humans. Bioinformatical analyses show that there are numerous amino acid or copy number-changing DNA variants of endurance genes in humans, suggesting that genetic variation of endurance genes contributes to the variation of human endurance capacity, too. Moreover, several of these genes/proteins change their expression or phosphorylation in skeletal muscle or the heart after endurance exercise, suggesting a role in the adaptation to endurance exercise.
PubMed: 30967789
DOI: 10.3389/fphys.2019.00262 -
Animals : An Open Access Journal From... Sep 2020Adiponectin is an abundant plasma protein that is closely related to obesity and obesity-related pathologies. The molecule can be found in three different isoforms, each...
Adiponectin is an abundant plasma protein that is closely related to obesity and obesity-related pathologies. The molecule can be found in three different isoforms, each with different biological activities. Studies on canine obesity have suggested that adiponectin concentrations are decreased in obesity; however, no canine meta-analyses have been performed that feature all the required data. The aim of this study is to perform a systematic review and meta-analysis of studies that pertain to total and high molecular weight (HMW) adiponectin in relation to canine obesity. From 20 different studies, a total of 366 dogs with obesity and 349 normal weight dogs are included in the meta-analysis. Client-owned dogs were most represented, accounting for 54.3% of the dogs used, while experimental dogs enrolled in the studies made up the remaining 45.7%. The concentrations of total adiponectin in dogs with obesity were significantly lower compared with normal weight dogs. Additionally, adiponectin concentrations were significantly higher in dogs after a successful weight loss protocol compared to the start of the protocol and were significantly lower in dogs after gaining weight. In conclusion, although caution should be taken due to the relatively low number of studies that exist and the high heterogeneity between them, this meta-analysis indicates that adiponectin is decreased in obese dogs.
PubMed: 32937899
DOI: 10.3390/ani10091650