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Arteriosclerosis, Thrombosis, and... Mar 2020Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current...
OBJECTIVE
Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain.
CONCLUSIONS
Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.
Topics: Acetylation; Animals; Fibrinogen; Fibrinolysis; Glycosylation; Humans; Oxidation-Reduction; Polymerization; Protein Processing, Post-Translational; Thrombosis
PubMed: 31914791
DOI: 10.1161/ATVBAHA.119.313626 -
Pathology Oncology Research : POR Jul 2020Previous studies indicated that cyclin D1 shown the potential as a tumor biomarker. However, the prognostic value of cyclin D1 in renal cell carcinoma (RCC) remains... (Meta-Analysis)
Meta-Analysis
Previous studies indicated that cyclin D1 shown the potential as a tumor biomarker. However, the prognostic value of cyclin D1 in renal cell carcinoma (RCC) remains controversial. This study investigated the correlation of cyclin D1 expression with the prognostic and clinicopathological features in RCC patients. We systematically searched the database of PubMed, Embase, Cochrane, and Web of Science updated on November 26, 2017. Eighteen studies with 2282 patients satisfied the inclusion criteria. Results demonstrated that cyclin D1 overexpression in RCC showed significant favorable prognostic impact on disease-free survival (DFS) (HR 0.57, 95% CI: 0.43-0.74) and disease-specific survival (DSS) (HR 0.59, 95% CI 0.41-0.85) without significant heterogeneity. In subgroup of clear cell RCC, the prognostic effect on DFS was robust and the pooled HR was 0.39 (95% CI: 0.27-0.57). However, no association between overall survival (OS) and cyclin D1 expression was observed. Stratified analysis in DFS studies by sample size, staining patterns race and metastasis status showed similar results. Otherwise, cyclin D1 overexpression predicted a reduced prevalence of high TNM stage (T3 + T4) (OR 0.63, 95% CI: 0.40-0.99), high-grade tumor (G3 + G4) (OR 0.51, 95% CI: 0.31-0.81) and large tumor size (OR 0.35, 95% CI: 0.19-0.62). Our meta-analysis indicated that cyclin D1 overexpression could predict the favorable prognosis in patients with RCC.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Cyclin D1; Humans; Kidney Neoplasms; Prognosis
PubMed: 31748879
DOI: 10.1007/s12253-019-00776-0 -
Systematic Reviews Nov 2019Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other...
BACKGROUND
Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS.
METHODS
Medline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells' features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist.
RESULTS
Seventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies.
CONCLUSION
A consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.
Topics: Cell Degranulation; Cytokines; Cytotoxicity, Immunologic; Fatigue Syndrome, Chronic; Granzymes; Humans; Killer Cells, Natural; Perforin; Phenotype
PubMed: 31727160
DOI: 10.1186/s13643-019-1202-6 -
Medicine Nov 2019The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis was carried out to quantitatively evaluate the prognostic values of partial KIF members in cancer patients.
METHODS
Two well-known KIF members, KIF2A and KIF20A, were investigated to evaluate their potential values as novel prognostic biomarkers in human cancer. A comprehensive literature search was carried out of the PubMed, EMBASE, Cochrane Library, and Web of Science databases up to April 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of KIF2A and KIF20A expression with overall survival (OS) and clinicopathological parameters.
RESULTS
Twenty-five studies involving 7262 patients were finally incorporated, including nine about KIF2A and sixteen about KIF20A. Our results indicated that patients with high expression of KIF2 and KIF20A tended to have shorter OS than those with low expression (HR = 2.23, 95% CI = 1.87-2.65, P < .001; HR = 1.77, 95% CI = 1.57-1.99, P < .001, respectively). Moreover, high expression of these 2 KIF members was significantly associated with advanced clinical stage (OR = 1.98, 95% CI: 1.57-2.50, P < .001; OR = 2.63, 95% CI: 2.03-3.41, P < .001, respectively), positive lymph node metastasis (OR = 2.32, 95% CI: 1.65-3.27, P < .001; OR = 2.13, 95% CI: 1.59-2.83, P < .001, respectively), and distant metastasis (OR = 2.20, 95% CI: 1.21-3.99, P = .010; OR = 5.25, 95% CI: 2.82-9.77, P < .001, respectively); only high KIF20A expression was related to poor differentiation grade (OR = 1.82, 95% CI: 1.09-3.07, P = .023).
CONCLUSIONS
High expression of KIF2 and KIF20A in human cancer was significantly correlated with worse prognosis and unfavorable clinicopathological features, suggesting that these 2 KIF members can be used as prognostic biomarkers for different types of tumors.
PROSPERO REGISTRATION NUMBER
CRD42019134928.
Topics: Biomarkers, Tumor; Humans; Kinesins; Lymphatic Metastasis; Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 31725680
DOI: 10.1097/MD.0000000000018040 -
Journal of Cerebral Blood Flow and... Dec 2019Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may... (Meta-Analysis)
Meta-Analysis
Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood-brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: -3.02; 95% confidence intervals: -4.41, -1.63; < 0.001; = 171 animals) and improved blood-brain barrier integrity (standardized mean difference: -2.02; 95% confidence intervals: -3.27, -0.77; = 0.002; = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood-brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.
Topics: Angiopoietin-1; Animals; Blood-Brain Barrier; Cerebral Infarction; Disease Models, Animal; Humans; Mice; Rats; Stroke; Up-Regulation
PubMed: 31581897
DOI: 10.1177/0271678X19876876 -
BMJ Open Aug 2019Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.
DESIGN
An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.
DATA SOURCES
Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.
ELIGIBILITY CRITERIA
The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.
DATA EXTRACTION AND SYNTHESIS
Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.
RESULTS
The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).
CONCLUSION
Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.
Topics: AMP-Activated Protein Kinase Kinases; Disease-Free Survival; Humans; Neoplasms; Prognosis; Protein Serine-Threonine Kinases; Survival Rate
PubMed: 31383697
DOI: 10.1136/bmjopen-2018-027185 -
Pathology Oncology Research : POR Apr 2020The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance... (Meta-Analysis)
Meta-Analysis
The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance of androgen receptor expression in renal cell carcinoma. A computerized bibliographic search of Embase, the PubMed, and Web of Science combined with manual research between 1977 and 2017 was conducted to explore the association between androgen receptor expression and clinicopathological features of renal cell carcinoma. Data were analyzed by a meta-analysis using RevMan 5.3 analysis software. Eleven retrospective studies with 1839 renal cell carcinoma cases were finally included according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05). However, positive androgen receptor expression was demonstrated to be significantly associated with male patients, lower pathological grade, and earlier tumor stage of renal cell carcinoma (OR = 1.69, 95% CI = 1.30-2.19, P < 0.0001; OR = 2.06, 95% CI = 1.49-2.85, P < 0.0001; OR = 2.81, 95% CI = 1.30-6.12, P = 0.009; respectively). In conclusion, higher androgen receptor expression was correlated with male patients, low tumor grade and early stage of renal cell carcinoma. Based on current results, androgen receptor-inhibited target therapy for renal cell carcinoma patients may be of limited benefits and should be taken into more evaluations.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Prognosis; Receptors, Androgen; Risk Factors
PubMed: 30919276
DOI: 10.1007/s12253-019-00650-z