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Neurosurgical Review Apr 2022Biomarkers such as calcium channel binding protein S100 subunit beta (S100B), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and... (Meta-Analysis)
Meta-Analysis Review
S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy.
Biomarkers such as calcium channel binding protein S100 subunit beta (S100B), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neuron-specific enolase (NSE) have been proposed to aid in screening patients presenting with mild traumatic brain injury (mTBI). As such, we aimed to characterise their accuracy at various thresholds. MEDLINE, SCOPUS and EMBASE were searched, and articles reporting the diagnostic performance of included biomarkers were eligible for inclusion. Risk of bias was assessed using the QUADAS-II criteria. A meta-analysis was performed to assess the predictive value of biomarkers for imaging abnormalities on CT. A total of 2939 citations were identified, and 38 studies were included. Thirty-two studies reported data for S100B. At its conventional threshold of 0.1 μg/L, S100B had a pooled sensitivity of 91% (95%CI 87-94) and a specificity of 30% (95%CI 26-34). The optimal threshold for S100B was 0.72 μg/L, with a sensitivity of 61% (95% CI 50-72) and a specificity of 69% (95% CI 64-74). Nine studies reported data for GFAP. The optimal threshold for GFAP was 626 pg/mL, at which the sensitivity was 71% (95%CI 41-91) and specificity was 71% (95%CI 43-90). Sensitivity of GFAP was maximised at a threshold of 22 pg/mL, which had a sensitivity of 93% (95%CI 73-99) and a specificity of 36% (95%CI 12-68%). Three studies reported data for NSE and two studies for UCH-L1, which precluded meta-analysis. There is evidence to support the use of S100B as a screening tool in mild TBI, and potential advantages to the use of GFAP, which requires further investigation.
Topics: Biomarkers; Brain Concussion; Brain Injuries, Traumatic; Diagnostic Tests, Routine; Glial Fibrillary Acidic Protein; Humans; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Ubiquitin Thiolesterase
PubMed: 34709508
DOI: 10.1007/s10143-021-01678-z -
Journal of Cosmetic Dermatology Dec 2022The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or... (Review)
Review
BACKGROUND
The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or misfolding, while finely regulating proteins involved in differentiation and other biological processes.
AIMS
The aim of this review is to systematically introduce UPS as a key regulator of melanin metabolism.
METHODS
Systematic search and retrospective review were performed on the published data.
RESULTS
Melanocyte-inducing transcription factor (MITF) is a substrate of the ubiquitin ligase VCHL1 and acts as a transcription factor to regulate the expression of key enzymes in melanin synthesis such as tyrosinase (TYR). The rate-limiting enzyme TYR is modified by the ubiquitin ligase Hrd1 during melanosynthesis. Melanin itself is also regulated by multiple ubiquitin ligases including Fbp1 and Vhl. By regulating the ubiquitination modification to target each link of melanin synthesis, it plays an important role in correcting the disorder of melanin metabolism. A number of chemical agents have been proven to inhibit the activity of ubiquitin ligase.
CONCLUSIONS
Drugs targeting E3 ligase and deubiquitinating enzymes have great potential in the treatment of melanin metabolism disorders.
Topics: Humans; Melanins; Proteasome Endopeptidase Complex; Transcription Factors; Ubiquitin; Ubiquitin-Protein Ligases
PubMed: 36207998
DOI: 10.1111/jocd.15433 -
Medical Oncology (Northwood, London,... Aug 2016C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an... (Review)
Review
C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an evolutionarily conserved and multifunctional protein that involves in controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair. The CSN is a highly conservative protein from yeast to human and interacts with the cullin-RING family of ubiquitin ligases so that it could be execute a process of removing NEDD8, a ubiquitin-like polypeptide (deneddylase activity). The role of Jab1/CSN5's multi-function has been proved as being oncogenic in nature, what is more, Jab1/CSN5 has been confirmed by much evidence that it participates in the carcinogenesis progression and is tightly associated with poor prognosis. However, the biologic implication of Jab1/CSN5 activity during the cancer's development is unclear. We performed a systematic literature review and assessment from PubMed and Medline databases in this article. Jab1/CSN5 is participate in a lot of biologic responses, including cell proliferation, apoptosis, cell cycle regulation, DNA metabolism, invasion, DNA damage and repair, and recurrence. It also promotes cell transformation and tumorigenesis. In this review, we mainly expound the progress in the function and research advances of Jab1/CSN5 and in untangling the Jab1/CSN5 signaling pathway. Based on these bases, its potential as a therapeutic target for cancer can play a greater role in future cancer treatment.
Topics: Animals; COP9 Signalosome Complex; Carcinogenesis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Peptide Hydrolases; Signal Transduction
PubMed: 27412572
DOI: 10.1007/s12032-016-0805-1 -
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 -
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 -
The Journal of Investigative Dermatology Jun 2024A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles...
A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 sequence variants from 2016 to August 2023 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data from 177 patients from 65 articles were retrieved (108 women). The principal features were mucosal ulcers (n = 129); fever (n = 93) followed by gastrointestinal (n = 81); skin features (n = 76); autoimmunity (n = 61), including thyroiditis (n = 25) and lupus (n = 16); and joint involvements (n = 54). Five patients had died at the time of publication. In 54 of 63 patients, CRP was significantly elevated during flares, with a median of 51 mg/l. The most commonly used treatment included corticosteroids and nonsteroidal anti-inflammatory drugs (n = 32), TNF blockers (n = 29), colchicine (n = 28), and methotrexate (n = 14). TNFAIP3 variants impacted the ovarian tumor domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, reported sex, and variant type significantly impacted phenotype. A better understanding of the wide A20 haploinsufficiency phenotype could facilitate the diagnosis process. Much remains to be elucidated about pathogenesis and treatment to improve outcome in patients with A20 haploinsufficiency.
Topics: Tumor Necrosis Factor alpha-Induced Protein 3; Humans; Haploinsufficiency; Female; Male; Hereditary Autoinflammatory Diseases
PubMed: 38128752
DOI: 10.1016/j.jid.2023.12.007 -
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 -
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 -
Autoimmunity Reviews Aug 2018Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the... (Review)
Review
INTRODUCTION
Behçet disease (BD) is a systemic vasculitis involving vessels from any size with various clinical features. Most BD cases are multifactorial and associated with the HLA B51 antigen. In rare and severe early onset cases, dominant Mendelian transmission has been linked to mutations in the TNFAIP3 gene encoding A20. Herein, we propose a systematic review of the literature about the haploinsufficiency A20 (HA20) published cases.
SYSTEMATIC REVIEW
Our review of the 45 cases of HA20 from literature highlights the similarities and the differences between this genetic auto-inflammatory disease and classical BD. HA20 looks like BD if we consider recurrent oral (87%) and genital (67%) ulcers, arthralgia or arthritis (42%), skin involvement (53%) such as erythema nodosum or abdominal symptoms (60%) such as abdominal pain, digestive ulcers or diarrhea. However, HA20 differs from classical BD because its geographical distribution is ubiquitous, sex ratio is inversed (one man for two women), first symptoms occur in early childhood (median age = 5.5 years; interquartile range: 1-10) instead of adulthood, recurrent fever is common (62%) unlike classical BD, HLA B51 antigen is uncommon and abdominal symptoms are over-represented compared to classical BD. In addition, response to colchicine in HA20 is inconstant (24%) unlike classical BD.
DISCUSSION/CONCLUSION
High fever flares and digestive involvement starting in early childhood seem to be hallmarks of HA20 clinical features. Response to colchicine is unpredictable and biotherapies like anti-TNFα and anti IL1 appear to be treatments of choice, like for other auto-inflammatory diseases. Prospective description of larger cohort of HA20 cases is needed to understand better when this disease must be looked for and how to treat these patients.
Topics: Behcet Syndrome; Genes, Dominant; Genetic Predisposition to Disease; Haploinsufficiency; Humans; Tumor Necrosis Factor alpha-Induced Protein 3
PubMed: 29890348
DOI: 10.1016/j.autrev.2018.02.012