-
Cerebrovascular Diseases (Basel,... 2022Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS.
METHODS
The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2).
RESULTS
The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality.
CONCLUSION
Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.
Topics: Biomarkers; Brain Ischemia; Ferritins; Hemorrhage; Humans; Ischemic Stroke; Matrix Metalloproteinase 9; Prognosis; Reproducibility of Results; Stroke
PubMed: 34569521
DOI: 10.1159/000518570 -
Medicine Sep 2021The results of how matrix metalloproteinases (MMPs) polymorphisms affect esophageal cancer (EC) risk are not consistent, especially for MMP1,2,7 and 9. A meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The results of how matrix metalloproteinases (MMPs) polymorphisms affect esophageal cancer (EC) risk are not consistent, especially for MMP1,2,7 and 9. A meta-analysis focused on the impact of MMPs to digestive cancers, but not a precise analysis to EC, therefore, we designed the current study to make a clear understanding of the association between MMPs polymorphisms and EC.
METHODS
Up to March 2020, we searched several databases to find case-control cohorts concerned about the risk of MMPs polymorphisms to EC risk. Odds ratios with 95% confidence intervals under five genetic models to generate the risk predicted value. The Q test and I2 statistics are used to estimate heterogeneity. Sensitivity analysis, Egger test, and Begg's funnel plot were employed to assess the results. In-silico analysis was performed to study the association between the polymorphism and mRNA expression.
RESULTS
19 case-control studies were enrolled, including 8371 EC patients and 12041 health controls. We observed the increased risk in BA vs. AA and BB + BA vs. AA models of MMP1-rs1799750 polymorphism. The protective effectiveness of EC was found in the MMP2 rs243865 polymorphism in B vs. A, BA vs. AA, and BB + BA vs. AA models. Meanwhile, the risk effect was also observed in the MMP7 rs11568818 polymorphism in most genetic models. In the furthermore bioinformatics analysis, we found that MMP1, MMP3, MMP7, MMP9, MMP12, MMP13 all increased in the tumor tissues, and the genetic alteration in the polymorphisms could impact the mRNA expression of the above MMPs.
CONCLUSION
MMP1 rs1799705 and MMP7 rs1156818 polymorphisms will take part in the tumorigenesis of EC, while MMP2 rs243865 acts as a protective role to decrease the risk of EC.
Topics: Esophageal Neoplasms; Genetic Predisposition to Disease; Humans; Matrix Metalloproteinases; Odds Ratio; Polymorphism, Genetic; Risk Factors
PubMed: 34559117
DOI: 10.1097/MD.0000000000027229 -
The role of matrix metalloproteinase-9 and its inhibitor TIMP-1 in burn injury: a systematic review.International Journal of Burns and... 2021Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators... (Review)
Review
Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators of the wound healing process. The aim of this systematic review was to determine the local and systemic involvement of the MMP-9/TIMP-1 system following burn injury. Two databases (Scopus and MEDLINE) were searched for all studies reporting MMP-9 and/or TIMP-1 after burn injury. Based on our eligibility criteria, we reviewed 24 studies involving 508 burns patients in 11 clinical studies and 367 animals in 13 preclinical studies. Local, systemic, and peripheral gene expression, protein levels and activity of MMP-9 and TIMP-1 were assessed. Increased MMP-9 was reported at the site of injury early after burn trauma in all studies, and remained elevated in non-healing wounds. Increased TIMP-1 expression in burn wounds occurred later than MMP-9, and was persistent in hypertrophic burn scars. Similar to local expression, systemic MMP-9 and TIMP-1 concentrations were significantly elevated after burn injury in response to upregulation of proinflammatory cytokines. While no association was found between systemic MMP-9 concentration and extent of injury or outcome, serum or plasma TIMP-1 showed good correlation with survival and burn severity. This review also found evidence of the MMP-9/TIMP-1 system contributing to secondary tissue damage distant from the burn site, including burn-associated musculoskeletal damage and acute lung injury. In addition, increased MMP-9 synthesis and activity in the brain after peripheral burn may lead to blood-brain barrier dysfunction and cerebral edema, a significant contributor to mortality. This systematic review provides an overview of the available evidence of the role of MMP-9 and TIMP-1 in burn injury pathophysiology and finds that TIMP-1 may be a promising biomarker in outcome prognostication of burns patients. Large-scale studies of both pediatric and adult burns patients with increased female representation and repeated sampling are recommended to validate the reliability of TIMP-1 as a prognostic marker following burn injury.
PubMed: 34557330
DOI: No ID Found -
Digestion 2021The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several...
INTRODUCTION
The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins.
METHODS
A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence.
RESULTS
The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data.
CONCLUSIONS
None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
Topics: Biomarkers; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Severity of Illness Index
PubMed: 34518458
DOI: 10.1159/000518419 -
Cancer Control : Journal of the Moffitt... 2021Studies have published the association between the expression of matrix metalloproteinases (MMPs) and the outcome of cervical cancer. However, the prognostic value in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Studies have published the association between the expression of matrix metalloproteinases (MMPs) and the outcome of cervical cancer. However, the prognostic value in cervical cancer remains controversial. This meta-analysis was conducted to evaluate the prognostic functions of MMP expression in cervical cancer.
METHODS
A comprehensive search of PubMed, Embase, and Web of Science databases was conducted to identify the eligible studies according to defined selection and excluding criteria and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Fixed and random effects models were evaluated through the hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the overall survival (OS), recurrence-free survival (RFS), and progress-free survival (PFS).
RESULTS
A total of 18 eligible studies including 1967 patients were analyzed for prognostic value. Totally 16 selected studies including 21 tests were relevant to the cervical cancer OS, 4 studies focused on RFS, and 1 study on PFS. The combined pooled HRs and 95% CIs of OS were calculated with random-effects models (HR = 1.64, 95% CI = 1.01-2.65, = .000). In the subgroup analysis for OS, there was no heterogeneity in MMP-2 (I = .0%, = .880), MMP-1 (I = .0%, = .587), and MMP-14 (I = 28.3%, = .248). In MMP-7 and MMP-9, the heterogeneities were obvious (I = 99.2% ( = .000) and I = 77.9% ( = .000), respectively). The pooled HRs and 95% CIs of RFS were calculated with fixed-effects models (HR = 2.22, 95% CI = 1.38-3.58, = .001) and PFS (HR = 2.29, 95% CI = 1.14-4.58, = .035).
CONCLUSIONS
The results indicated that MMP overexpression was associated with shorter OS and RFS in cervical cancer patients. It suggested that MMP overexpression might be a poor prognostic marker in cervical cancer. Research Registry Registration Number: reviewregistry 1159.
Topics: Biomarkers, Tumor; Female; Humans; Matrix Metalloproteinases; Progression-Free Survival; Uterine Cervical Neoplasms
PubMed: 34482737
DOI: 10.1177/10732748211033743 -
Postepy Dermatologii I Alergologii Feb 2021Matrix metalloproteinases (MMPs) play a pivotal role in the cancer progression, invasion, and angiogenesis. (Review)
Review
INTRODUCTION
Matrix metalloproteinases (MMPs) play a pivotal role in the cancer progression, invasion, and angiogenesis.
AIM
This meta-analysis was conducted to evaluate the difference between oral squamous cell carcinoma (OSCC) patients and healthy controls in the serum and salivary MMP levels.
MATERIAL AND METHODS
Four databases - Web of Science, PubMed, Scopus, and Cochrane Library - were searched up to March 2019. The pooled standard mean difference (SMD) and 95% confidence interval (CI) were obtained to explain the difference between the patients and controls in the salivary and serum MMP levels. Both Egger's and Begg's tests were considered as the significant publication bias.
RESULTS
Thirteen case-control studies were included in the meta-analysis. Among the analyses of serum MMP levels, the serum MMP7 (SMD = 0.78; 95% CI: 0.15-1.41; = 0.02) and MMP9 (SMD = 1.18; 95% CI: 0.51-1.84; = 0.0005) levels were significantly higher in the OSCC patients than in the controls. In addition, the analyses of salivary MMP levels showed that the MMP1 (SMD = 0.46; 95% CI: 0.22-0.70; = 0.0001) and MMP9 (SMD = 0.66; 95% CI: 0.19-1.12; = 0.005) levels were significantly higher in the OSCC patients than in the controls.
CONCLUSIONS
The meta-analysis showed that the serum MMP7 and MPP9 levels as well as the salivary MMP1 and MPP9 levels were significantly higher in the OSCC patients than in the controls.
PubMed: 34408576
DOI: 10.5114/ada.2021.104285 -
Medicine Aug 2021Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.
METHODS
We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.
RESULTS
High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.
CONCLUSION
High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 14; Prognosis; Stomach Neoplasms
PubMed: 34397871
DOI: 10.1097/MD.0000000000026545 -
Vascular Medicine (London, England) Feb 2022Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management...
Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management relies exclusively on surgical repair as there is no effective medical therapy. A key element of AAA pathogenesis is the chronic inflammation mediated by inflammatory cells releasing proteases, including the enzyme dipeptidyl peptidase IV (DPP-IV). This review sought to recapitulate available evidence on the involvement of DPP-IV in AAA development. Further, we assessed the experimental use of currently available DPP-IV inhibitors for AAA management in murine models. Embase, Medline, PubMed, and Web of Science databases were utilised to access the relevant studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A narrative synthesis approach was used. Sixty-four studies were identified from the searched databases; a final 11 were included in the analysis. DPP-IV was reported to be significantly increased in both AAA tissue and plasma of patients and correlated with AAA growth. DPP-IV inhibitors (sitagliptin, vildagliptin, alogliptin, and teneligliptin) were all shown to attenuate AAA formation in murine models by reducing monocyte differentiation, the release of reactive oxygen species (ROS), and metalloproteinases (MMP-2 and MMP-9). DPP-IV seems to play a role in AAA pathogenesis by propagating the inflammatory microenvironment. This is supported by observations of decreased AAA formation and reduction in macrophage infiltration, ROS, matrix MMPs, and interleukins following the use of DPP-IV inhibitors in murine models. There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.
Topics: Animals; Aortic Aneurysm, Abdominal; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Macrophages; Mice; Sitagliptin Phosphate
PubMed: 34392748
DOI: 10.1177/1358863X211034574 -
Journal of Ovarian Research Aug 2021In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted.
AIM
In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted.
METHODS
In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research.
RESULTS
In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis.
CONCLUSIONS
From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation.
Topics: Female; Humans; Immunohistochemistry; Matrix Metalloproteinase 14; Ovarian Neoplasms; Survival Analysis
PubMed: 34344453
DOI: 10.1186/s13048-021-00852-7 -
Environmental Health Perspectives Jul 2021Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), may play a role in the pathogenesis...
BACKGROUND
Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD), may play a role in the pathogenesis of endometriosis.
OBJECTIVES
We aimed to systematically review the experimental evidence ( and ) on the associations between exposure to OCCs and endometriosis-related end points.
METHODS
A systematic review protocol was developed following the National Toxicology Program /Office of Health Assessment and Translation (NTP/OHAT) framework and managed within a web-based interface. studies designed to evaluate the impact of OCCs on the onset or progression of endometriosis and proliferation of induced endometriotic lesions were eligible. Eligible studies included single-cell and co-culture models to evaluate the proliferation, migration, and/or invasion of endometrial cells. We applied the search strings to PubMed, Web of Science, and Scopus®. A final search was performed on 24 June 2020. Assessment of risk of bias and the level of evidence and integration of preevaluated epidemiological evidence was conducted using NTP/OHAT framework Results: Out of 812 total studies, 39 met the predetermined eligibility criteria (15 , 23 , and 1 both). Most studies () tested TCDD and other dioxin-like chemicals. evidence supported TCDD's promotion of endometriosis onset and lesion growth. evidence supported TCDD's promotion of cell migration and invasion, but there was insufficient evidence for cell proliferation. evidence further supported the roles of the aryl hydrocarbon receptor and matrix metalloproteinases in mediating steroidogenic disruption and inflammatory responses. Estrogen interactions were found across studies and end points.
CONCLUSION
Based on the integration of a high level of animal evidence with a moderate level of epidemiological evidence, we concluded that TCDD was a known hazard for endometriosis in humans and the conclusion is supported by mechanistic evidence. Nonetheless, there is need for further research to fill in our gaps in understanding of the relationship between OCCs and their mixtures and endometriosis, beyond the prototypical TCDD. https://doi.org/10.1289/EHP8421.
Topics: Animals; Cell Culture Techniques; Cell Proliferation; Dioxins; Endometriosis; Environmental Exposure; Female; Humans; Hydrocarbons, Chlorinated; Polychlorinated Dibenzodioxins
PubMed: 34310196
DOI: 10.1289/EHP8421