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BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
International Journal of Molecular... Aug 2023As per the latest ILAE definition, status epilepticus (SE) may lead to long-term irreversible consequences, such as neuronal death, neuronal injury, and alterations in... (Review)
Review
As per the latest ILAE definition, status epilepticus (SE) may lead to long-term irreversible consequences, such as neuronal death, neuronal injury, and alterations in neuronal networks. Consequently, there is growing interest in identifying biomarkers that can demonstrate and quantify the extent of neuronal and glial injury. Despite numerous studies conducted on animal models of status epilepticus, which clearly indicate seizure-induced neuronal and glial injury, as well as signs of atrophy and gliosis, evidence in humans remains limited to case reports and small case series. The implications of identifying such biomarkers in clinical practice are significant, including improved prognostic stratification of patients and the early identification of those at high risk of developing irreversible complications. Moreover, the clinical validation of these biomarkers could be crucial in promoting neuroprotective strategies in addition to antiseizure medications. In this study, we present a systematic review of research on biomarkers of neuro-glial injury in patients with status epilepticus.
Topics: Animals; Humans; Neuroglia; Brain Injuries; Neurons; Status Epilepticus; Biomarkers; Glial Fibrillary Acidic Protein; Ubiquitin Thiolesterase
PubMed: 37569895
DOI: 10.3390/ijms241512519 -
Molecular Neurobiology Jan 2023Despite annual increases in the incidence and prevalence of neurodegenerative diseases, there is a lack of effective treatment strategies. An increasing number of E3... (Review)
Review
Despite annual increases in the incidence and prevalence of neurodegenerative diseases, there is a lack of effective treatment strategies. An increasing number of E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) have been observed to participate in the pathogenesis mechanisms of neurodegenerative diseases, on the basis of which we conducted a systematic literature review of the studies. This review will help to explore promising therapeutic targets from highly dynamic ubiquitination modification processes.
Topics: Humans; Ubiquitin-Protein Ligases; Neurodegenerative Diseases; Ubiquitination
PubMed: 36260224
DOI: 10.1007/s12035-022-03063-3 -
Asian Journal of Andrology 2022During recent decades, the association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility remains doubtful. We conducted this meta-analysis... (Meta-Analysis)
Meta-Analysis
During recent decades, the association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility remains doubtful. We conducted this meta-analysis to evaluate the association between mutations in USP26 and male infertility according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021225251). PubMed, Web of Science, and Scopus were systematically searched for comparative clinical studies, which were written in English and provided eligible data. Studies were included when they compared USP26 mutations in azoospermic, oligozoospermic, and asthenozoospermic patients with controls with normal sperm parameter values or whose partners had experienced spontaneous pregnancy. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated with random effect models. Overall, twelve studies with 3927 infertility patients and 4648 healthy controls were included. The association between overall USP26 mutations and infertility was not significant (OR = 1.60, 95% CI: 0.51-5.01). For specific mutations, the pooled ORs were 1.65 (95% CI: 1.02-2.69) for cluster mutation (including 370-371insACA, 494T>C, and 1423C>T), 1.80 (95% CI: 0.35-9.15) for c.576G>A, 1.43 (95% CI: 0.79-2.56) for c.1090C>T, and 3.59 (95% CI: 2.30-5.59) for c.1737G>A. Our results suggest that several mutations (cluster mutation, c.1737G>A) may play roles in male infertility, while others (c.576G>A and c.1090C>T) do not show notable associations with male infertility. More high-quality clinical researches are needed for validation.
Topics: Cysteine Endopeptidases; Female; Humans; Infertility, Male; Male; Mutation; Pregnancy; Semen; Ubiquitin-Specific Proteases
PubMed: 35074940
DOI: 10.4103/aja2021109 -
Journal of Cellular and Molecular... Mar 2021c-Jun activation domain-binding protein-1 (Jab1) is aberrantly overexpressed in multiple cancers and plays an oncogenic role in cancer progression. We examined the... (Meta-Analysis)
Meta-Analysis
c-Jun activation domain-binding protein-1 (Jab1) is aberrantly overexpressed in multiple cancers and plays an oncogenic role in cancer progression. We examined the association between Jab1 expression and prognosis in patients with cancer by conducting a meta-analysis. A comprehensive search strategy was performed using the PubMed, Web of Science, Ovid and EMBASE in July 2020. Eligible studies were enrolled according to definite criteria. Twenty-seven studies involving 2609 patients were enrolled in this meta-analysis. A significant association between high Jab1 expression and poor overall survival (pooled hazard ratio [HR] 2.344, 95% confidence interval [CI]: 2.037-2.696) was observed. Subgroup analyses of the type of cancer, sample size, follow-up period, Jab1 detection method and preoperative treatment did not alter the significance. On pooling data from Cox multivariate analyses, high Jab1 expression was found to be an independent prognostic indicator for overall survival. In addition, high Jab1 expression was found to be associated with advanced clinicopathological features such as clinical stage, lymphatic metastasis, histological grade and distant metastasis in cancers. Our meta-analysis is the first to demonstrate that high Jab1 expression may be a promising indicator of poor prognosis and has an independent prognostic value for overall survival in patients with cancer.
Topics: Biomarkers, Tumor; COP9 Signalosome Complex; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Neoplasm Staging; Neoplasms; Peptide Hydrolases; Prognosis; Proportional Hazards Models; Publication Bias
PubMed: 33550701
DOI: 10.1111/jcmm.16334 -
Sports Medicine and Arthroscopy Review Sep 2016Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review... (Review)
Review
Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
Topics: Biomarkers; Brain Concussion; Glial Fibrillary Acidic Protein; Humans; Magnetic Resonance Imaging; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Ubiquitin Thiolesterase; tau Proteins
PubMed: 27482776
DOI: 10.1097/JSA.0000000000000117 -
The Cochrane Database of Systematic... Jul 2016About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard... (Review)
Review
BACKGROUND
About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series.
OBJECTIVES
To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision-making to undertake diagnostic surgery for endometriosis.
SEARCH METHODS
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
SELECTION CRITERIA
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
MAIN RESULTS
Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear.
AUTHORS' CONCLUSIONS
None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.
Topics: Aromatase; Biomarkers; CA-125 Antigen; CA-19-9 Antigen; Endometriosis; Female; Humans; Interleukin-6; Leukocytes; Ovarian Diseases; Pelvis; Peritoneal Diseases; Phosphopyruvate Hydratase; Sensitivity and Specificity; Ubiquitin Thiolesterase; Ultrasonography; Vitamin D-Binding Protein
PubMed: 27405583
DOI: 10.1002/14651858.CD012281 -
CNS Neuroscience & Therapeutics Aug 2013Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and... (Review)
Review
Rapid triage and decision-making in the treatment of traumatic brain injury (TBI) present challenging dilemma in "resource poor" environments such as the battlefield and developing areas of the world. There is an urgent need for additional tools to guide treatment of TBI. The aim of this review is to establish the possible use of diagnostic TBI biomarkers in (1) identifying diffuse and focal brain injury and (2) assess their potential for determining outcome, intracranial pressure (ICP), and responses to therapy. At present, there is insufficient literature to support a role for diagnostic biomarkers in distinguishing focal and diffuse injury or for accurate determination of raised ICP. Presently, neurofilament (NF), S100β, glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1) seemed to have the best potential as diagnostic biomarkers for distinguishing focal and diffuse injury, whereas C-tau, neuron-specific enolase (NSE), S100β, GFAP, and spectrin breakdown products (SBDPs) appear to be candidates for ICP reflective biomarkers. With the combinations of different pathophysiology related to each biomarker, a multibiomarker analysis seems to be effective and would likely increase diagnostic accuracy. There is limited research focusing on the differential diagnostic properties of biomarkers in TBI. This fact warrants the need for greater efforts to innovate sensitive and reliable biomarkers. We advocate awareness and inclusion of the differentiation of injury type and ICP elevation in further studies with brain injury biomarkers.
Topics: Animals; Biomarkers; Brain Injuries; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Spectrin; Ubiquitin Thiolesterase; tau Proteins
PubMed: 23710877
DOI: 10.1111/cns.12127 -
PloS One 2011As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized... (Review)
Review
As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family.
Topics: Databases, Protein; Deubiquitinating Enzyme CYLD; Dystroglycans; Genetic Predisposition to Disease; Genome-Wide Association Study; Hepatocyte Growth Factor; Humans; Inflammatory Bowel Diseases; Peptide Hydrolases; Protease Inhibitors; Proto-Oncogene Proteins; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Ubiquitin-Specific Proteases
PubMed: 21931648
DOI: 10.1371/journal.pone.0024106