-
Cytokine Aug 2023The matrix metalloproteinases (MMPs) are engaged in the degradation and remodeling of the extracellular matrix and vessels, allowing the progression of pathological... (Review)
Review
The matrix metalloproteinases (MMPs) are engaged in the degradation and remodeling of the extracellular matrix and vessels, allowing the progression of pathological processes. Recent studies pointed that MMP -2 and -9 are promising visceral leishmaniasis biomarkers. Thus, the present studystudy aimed to review published scientific literature related to MMP-2 and -9 activity on canine visceral leishmaniasis (CVL). The review followed the PRISMA method, searching for articles in ScienceDirect, PubMed, Scopus, Lilacs, Medline and Google Scholar from inception until 20 March 2022 by employing the following terms: "dog", "matrix metalloproteinases" and "Visceral Leishmaniasis" or "Kala Azar". The selected articles were read in full and only those consistent with the eligibility criteria were included in the review. Of 238 articles from the initial search, only five were deemed eligible, which were conducted between 2010 and 2018. All studies were performed in Brazil. It was observed that there was a higher expression of proMMP-2 in cerebrospinal (CS) fluid and serum and active MMP-2 in different skin areas, mainly in high parasite load areas. As for MMP-9, the pro and active forms were both expressed in CS fluid, serum and different skin areas. The MMP-2 can be considered a biomarker of bad prognostic as it plays an inflammatory role with a greater release in the initial phase of the disease, where MMP-9 is perceived in the chronic phase of CVL. Future research on the subject with greater methodological rigor and bigger sample sizes are mandatory to clarify the role of MMPs on disease progression.
Topics: Dogs; Biomarkers; Leishmaniasis, Visceral; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Risk Factors; Animals
PubMed: 37257306
DOI: 10.1016/j.cyto.2023.156236 -
TouchREVIEWS in Endocrinology Nov 2023Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be... (Review)
Review
Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor β1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3 , neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-d esigned interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.
PubMed: 38187082
DOI: 10.17925/EE.2023.19.2.12 -
Medicine Oct 2023Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: "Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?"
METHODS
The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals.
RESULTS
A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001).
CONCLUSION
RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.
Topics: Humans; Matrix Metalloproteinase 8; Periodontitis; Arthritis, Rheumatoid; Cytokines; Biomarkers; Matrix Metalloproteinase 3
PubMed: 37832126
DOI: 10.1097/MD.0000000000035340 -
International Journal of Molecular... Sep 2023Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute... (Review)
Review
Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.
Topics: Humans; NF-kappa B; Intracranial Aneurysm; Signal Transduction; Arteries; Inflammation
PubMed: 37762520
DOI: 10.3390/ijms241814218 -
Frontiers in Psychiatry 2023While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and... (Review)
Review
BACKGROUND
While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and sometimes sparse observations. We conducted a comprehensive meta-analysis to critically assess the alterations of vascular-related molecules in the cerebrospinal fluid (CSF) and blood of patients with psychotic disorders compared with healthy individuals.
METHODS
Databases were searched from inception to February 23, 2023. Meta-analyses were performed using a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effects of clinical correlates.
RESULTS
We identified 93 eligible studies with 30 biomarkers investigated in the CSF and/or blood. Among the biomarkers examined, psychotic disorders were associated with elevated CSF-to-serum albumin ratio (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.35-1.02); blood S100B (SMD, 0.88; 95% CI, 0.59-1.17), matrix metalloproteinase-9 (MMP-9; SMD, 0.66; 95% CI, 0.46-0.86), and zonulin (SMD, 1.17; 95% CI, 0.04-2.30). The blood levels of S100B, MMP-9, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) were altered in patient subgroups differing in demographic and clinical characteristics. Blood S100B level was positively correlated with age and duration of illness. Substantial between-study heterogeneity was observed in most molecules.
CONCLUSION
The alterations in certain vascular-related fluid markers in psychotic disorders suggest disturbances in normal vascular structures and functions. However, not all molecules examined displayed clear evidence of changes. While potential impacts of clinical factors, including the administered treatment, were identified, the exploration remained limited. Further studies are needed to investigate the diverse patterns of expression, and understand how these abnormalities reflect the pathophysiology of psychosis and the impact of clinical factors.
PubMed: 37692299
DOI: 10.3389/fpsyt.2023.1241422 -
International Endodontic Journal Oct 2023Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however, their accuracy is unknown.
OBJECTIVES
(1) Calculate sensitivity, specificity and diagnostic odds ratio (DOR) of previously investigated pulpitic biomarkers; (2) Determine if biomarker levels discriminate between clinical diagnoses of pulpitis based on the presence or absence of spontaneous pain (3) Evaluate if biomarker level can predict VPT outcome.
METHODS
Searches: PubMed/MEDLINE, Ovid SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase, Web of Science and Scopus in May 2023.
INCLUSION
prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well-defined pulpal diagnosis.
EXCLUSION
deciduous teeth, in vitro and animal studies. Risk of bias was assessed with modified-Downs and Black quality assessment checklist. Meta-analysis was performed using bivariate random effect model in Meta-DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.
RESULTS
Fifty-six studies were selected, reporting >70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL-8 and IL-6 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low-certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy.
DISCUSSION
The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non-spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair.
CONCLUSIONS
Low-quality evidence suggests IL-8 and IL-6 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation.
REGISTRATION
PROSPERO CRD42021259305.
Topics: Humans; Pulpitis; Interleukin-6; Prospective Studies; Interleukin-8; Retrospective Studies; Biomarkers; Pain
PubMed: 37392154
DOI: 10.1111/iej.13950 -
Biomolecules Jul 2023The recurrence rate in patients who undergo surgery for abdominal wall hernias (AWHs) is high. AWHs have been hypothesized to be a disease of the extracellular matrix,... (Review)
Review
The recurrence rate in patients who undergo surgery for abdominal wall hernias (AWHs) is high. AWHs have been hypothesized to be a disease of the extracellular matrix, which is supported by evidence showing a high incidence of AWHs in patients with connective tissue disorders. This study aimed to investigate the most recent literature studies describing the levels of several matrix metalloproteinases (MMPs) in the blood and fascia, with the objective of better clarifying the pathogenetic role of matrix metalloproteinases (MMPs) and their inhibitors in inguinal hernias (IHs). A systematic literature search was conducted using the PubMed, Scopus, and Web of Science electronic databases to identify eligible studies. The identified studies were included in the analysis, and a qualitative synthesis of the results is provided to describe the most recent findings. Seventeen studies were included. An association between MMP-2 and direct IHs has also been demonstrated. MMP-1, MMP-2, MMP-9, MMP-12, and MMP-13 levels were increased in both the serum and fascia of patients with IHs. The analysis of inhibitors showed an increase in tissue inhibitors of metalloproteinases (TIMPs), specifically TIMP-1 in IHs, particularly in direct hernias, and a reduction in TIMP-2 in the biopsy samples of the transversalis fascia. In contrast, a reduction in TIMP-1 and an increase in TIMP-2 levels have been reported only in the serum of patients with IHs. Metalloproteinases play a crucial role in the pathogenesis of IHs. The analysis of other molecules, such as TIMPs or their correlation with specific genes, is enhancing our understanding of the pathophysiology of IHs. However, more prospective studies, including comprehensive clinical and laboratory data collection, are required to confirm the relationship between the studied biomarkers and the risk of IHs.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Hernia, Inguinal; Matrix Metalloproteinase 2; Prospective Studies; Tissue Inhibitor of Metalloproteinases
PubMed: 37509159
DOI: 10.3390/biom13071123 -
Journal of Clinical Periodontology May 2024To determine the accuracy of salivary active matrix metalloproteinase (aMMP)-8 point-of-care test (POCT) for detecting periodontitis in adults, through meta-analysis. (Review)
Review
OBJECTIVE
To determine the accuracy of salivary active matrix metalloproteinase (aMMP)-8 point-of-care test (POCT) for detecting periodontitis in adults, through meta-analysis.
MATERIALS AND METHODS
Diagnostic studies evaluating the accuracy of salivary/oral rinse aMMP-8 POCT for detecting periodontitis in adults, when compared with clinical examination, were considered eligible. A comprehensive search was performed up to 31 August 2023 through five databases. Quality Assessment of Diagnostic Accuracy Studies 2 was utilized to evaluate the methodological quality of the included articles. Meta-analysis was performed using Bayesian bivariate hierarchical model and subgroup analysis.
RESULTS
From 368 screened studies, 6 studies (4 cross-sectional and 2 longitudinal studies) were included in the meta-analysis. Overall, the pooled sensitivity and specificity of salivary aMMP-8-POCT for detecting periodontitis were 0.63 (95% CI: 0.41-0.82) and 0.84 (95% CI: 0.65-0.95), respectively. Subgroup analyses revealed that the 95% CI for oral fluid types, predefined diagnostic thresholds and the POCT systems largely overlapped, indicating that the differences between them may not be significant.
CONCLUSION
Salivary aMMP-8 POCT shows fair accuracy for detecting periodontitis. The diagnostic accuracy cannot be significantly influenced by the types of oral fluids, predefined diagnostic thresholds or the specific POCT systems used. More research is needed to confirm the clinical utility and implementation of aMMP-8 POCT in the diagnosis of periodontitis.
PubMed: 38763168
DOI: 10.1111/jcpe.14000 -
International Journal of Molecular... Apr 2024Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal... (Review)
Review
Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia's genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Placenta; Biomarkers; MicroRNAs; Hormones; Trophoblasts
PubMed: 38674114
DOI: 10.3390/ijms25084532 -
European Journal of Dentistry Oct 2023Matrix metalloproteinase (MMP) enzymes participate in collagen matrix degradation, including in dentine, potentially compromising bond strength. Therefore, MMP...
Impact of Dentine Pretreatment with Matrix Metalloproteinase Inhibitors on Bond Strength of Coronal Composite Restorations: A Systematic Review and Meta-analysis of In Vitro Studies.
Matrix metalloproteinase (MMP) enzymes participate in collagen matrix degradation, including in dentine, potentially compromising bond strength. Therefore, MMP inhibitors have been hypothesized to improve restoration bond strength and stability. This systematic review aimed to evaluate the influence of different MMP inhibitors applied as dentine surface pretreatments on the immediate (24 hours) and longer term (months) bond strength of direct coronal composite restorations. This systematic literature review followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. A systematic literature search of three databases (Ovid MEDLINE, Ovid Embase, and Google Scholar) was conducted independently by two reviewers from inception to April 2022. An adapted quality assessment tool was independently applied by two reviewers for risk of bias assessment. RevMan v5.4 software was used for meta-analyses. A randomeffectsmodel was used to generatemean differences with 95% confidence intervals for treatment and control comparisons. The Q-test and I2-test were used to test for heterogeneity. The proportion of total variance across studies attributable to heterogeneity rather than chance was calculated. Overall effects were tested using the Z-test, while subgroup differences were tested using Chi-squared tests. Of 934 studies, 64 studies were included in the systematic review and 42 in the meta-analysis. Thirty-one MMP inhibitors were reported, three of which were included in the meta-analysis: 2% chlorhexidine (CHX), 0.3M carbodiimide (EDC), and 0.1% riboflavin (RIBO). Pretreatment with 2% CHX for 30 and 60 seconds did not significantly improve bond strength compared with controls either immediately or after long-termageing. However, pretreatment with 0.3MEDC and 0.1% RIBO (but not CHX) significantly improved bond strength compared with control groups both immediately and over time. Most studies showed a medium risk of bias. These in vitro findings pave the way for rationale clinical trialing of dentine surface pretreatment with MMP inhibitors to improve clinical outcomes.
PubMed: 36400108
DOI: 10.1055/s-0042-1757582